Pan African Clinical Trials Registry

South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: www.pactr.org
Trial no.: PACTR202005681895696 Date of Approval: 11/05/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A study to determine if a new vaccine safely generates good immune responses to protect adults in Kenya from Coronavirus Disease
Official scientific title A phase Ib/II single-blinded, randomised, controlled study to determine safety, immunogenicity and efficacy of the candidate Coronavirus Disease (COVID-19) vaccine ChAdOx1 nCoV-19 in adults in Kenya (COV004)
Brief summary describing the background and objectives of the trial As of 11th September 2020, the COVID-19 pandemic has affected over 27 million people globally, with over 900,000 deaths. The disease has been reported in over 200 countries, including Kenya where over 35,000 cases have been reported. No vaccines or treatments are currently licensed for use against COVID-19. As the number of cases continue to rise globally, an effective vaccine remains the best way to control the pandemic and to safely relax physical distancing and other restrictions. There are over 30 COVID-19 vaccine candidates in clinical development. ChAdOx1 nCoV-19, developed by the University of Oxford in partnership with AstraZeneca, is the most advanced. ChAdOx1 nCoV-19 has shown promise in a range of animal models of COVID-19 disease and has already been administered to over 5,000 adult volunteers in the United Kingdom, Brazil and South Africa (Registration numbers: NCT04324606, NCT04400838, ISRCTN89951424 and NCT04444674). We plan to evaluate the safety and immunogenicity of a single dose of ChAdOx1 nCoV-19 (5x1010 vp) vaccine among 400 adults aged ≥18 years. The study will take place in the coastal counties of Kilifi and Mombasa, where high numbers of COVID-19 cases have been detected. The study will only enrol frontline workers in key service areas e.g. healthcare workers, allied health professionals, truckers, among others. These populations have been prioritised due to their high risk of occupational exposure to COVID-19, hence their urgent need for protection. Participants will be randomized to receive either ChAdOx1 nCoV-19 (n=200) or rabies vaccine (n=200). Out of these, 40 will be enrolled in the phase Ib trial, and the remainder to the phase II trial (180 per vaccine). If found to be safe and effective in generating protective immune responses, the ChAdOx1 nCoV-19 will be further developed for use in controlling COVID-19, including in populations in Kenya and other countries in Africa.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) COV004
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied COVID-19 Disease
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 01/10/2020
Actual trial start date
Anticipated date of last follow up 01/10/2022
Actual Last follow-up date 31/05/2022
Anticipated target sample size (number of participants) 400
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Sealed opaque envelopes Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group COVID19 vaccine Single dose of ChAdOx1 nCoV-19 vaccine 5x10^10 vp Phase Ib-1 year follow-up Phase II-1 year follow-up Phase Ib and II will be conducted within the same trial, phase II beginning after DSMB review of phase I day 28 data. ChAdOx1 nCoV-19 vaccine consists of the replication-deficient simian adenovirus vector ChAdOx1, containing the structural surface glycoprotein (Spike protein) antigen of the SARS CoV-2 (nCoV-19), with a leading tissue plasminogen activator (tPA) signal sequence. ChAdOx1 nCoV-19 expresses a codon-optimised coding sequence for the Spike protein from genome sequence accession GenBank: MN908947. The tPA leader sequence has been shown to be beneficial in enhancing immunogenicity of another ChAdOx1 vectored CoV vaccine (ChAdOx1 MERS) [5]. Following vaccination, the Spike glycoprotein (S) primes the host immune system to attack the coronavirus in case of any infections. The ChAdOx1 vaccine vector was selected due to its non-replicating nature, making it impossible to cause an infection in vaccinated individuals. As a result, the vaccine would be safe in individuals with pre-existing conditions and age groups at risk of getting the SARS-CoV-2 infection. 200
Control Group Rabies vaccine 0.5 mL of Verorab (rabies vaccine) via the intramuscular route. Single dose Phase Ib-1 year follow-up Phase II-1 year follow-up Phase Ib and II will be conducted within the same trial, phase II beginning after DSMB review of phase I day 28 data. Verorab (from Sanofi) will be used as the rabies vaccine and it is registered and licensed for use in Kenya. One dose consists in the administration of 0.5 mL of vaccine via the intramuscular route. 200 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• Frontline Staff as defined by the Government of Kenya • Healthy adults aged 18-55 years for phase Ib, ≥18 years for phase II. • Able and willing (in the Investigators’ opinion) to comply with all study requirements, including making visits to KEMRI CGMRC or other designated study health facility for follow up under conditions with limited transport. • Agreement to refrain from blood donation during the course of the study • Use of effective method of contraception for duration of study for female participants. They should use effective contraception for 30 days prior to vaccination. For female participants, we will ask them to attend with their family planning records for verification. Effective contraception is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly, in accordance with the product label. Examples of these include: combined oral contraceptives; injectable progestogen; implants of etenogestrel or levonorgestrel; intrauterine device or intrauterine system; male partner sterilisation at least 6 months prior to the female subject’s entry into the study, and the relationship is monogamous; male condom combined with a vaginal spermicide (foam, gel, film, cream or suppository); and male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository). • Provide written informed consent. • Plan to remain resident in the study area for 1 year following vaccination • Prior receipt of any vaccines (licensed or investigational) ≤30 days before enrolment • Volunteer who is not literate. • Planned receipt of any vaccine other than the study intervention within 30 days before or after study vaccination. • Prior receipt of an investigational or licensed vaccine likely to impact on interpretation of the trial data (e.g. Adenovirus vectored vaccines, any coronavirus vaccines). • Planned or ongoing participation in any other interventional studies (of licensed or investigational products) ≤30 days before enrolment and for the duration of the study. • Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate. • Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent severe infections and chronic use (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed). • History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. • Any history of hereditary or idiopathic angioedema. • Pregnancy, lactation or willingness/intention to become pregnant during the study. • History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ). • History of serious psychiatric condition likely to affect participation in the study. • Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture. • Any other serious chronic illness requiring hospital specialist supervision. • Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week (e.g. more than 2 bottles of 500mls Tusker (beer) a day, more than 2 large glasses of 12% wine per day) Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 55 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 04/05/2020 KEMRI Scientific and Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
Kenya Medical Research Institute, Off Mbagathi Way Nairobi. Postal address P.O. BOX 54840 Nairobi 00200 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome A. To assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1nCoV-19 1. Occurrence of serious adverse events (SAEs) throughout the study duration 2. Occurrence of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination 3. Occurrence of unsolicited adverse events (AEs) at all scheduled visits; 4. Change from baseline for safety laboratory measures and; 5. Occurrence of SAE of special interest: disease enhancement episodes B. To assess immunogenicity of ChAdOx1 nCoV-19 1. ELISA to quantify IgG antibodies against SARSCoV-2 spike protein (seroconversion rates) A1- Throughout the study, A2- Days 0 to 7, A3 and A5-Throughout the study, A4-day 7 and 28, B1-day 0 and 28
Secondary Outcome A. To assess humoral immunogenicity of ChAdOx1 nCoV-19 at early and late timepoints 1. ELISA to quantify IgG antibodies against SARS-CoV-2 spike protein (seroconversion rates) B. To assess cellular immunogenicity of ChAdOx1 nCoV-19 1. IFN-γ ELISpot responses to SARS-CoV-2 spike protein; C. To assess efficacy of ChAdOx1 nCoV-19 against COVID-19 1. Virologically confirmed (PCR positive) symptomatic cases of COVID-19 2. Hospital admissions associated with COVID-19 3. Deaths associated with COVID-19 4. Seroconversion against non-Spike antigens measured by ELISA 5. Asymptomatic SARS-CoV2 carriage day 0,14, 84 182, 365
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
KEMRI Wellcome Trust Research Programme Centre for Geographic Medicine Coast KWTRP CGMRC Hospital Grounds, Off Bofa Road, PO Box 230 Kilifi Kenya 80108 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
Wellcome Trust Gibbs Building 215 Euston Road London NW1 2BE UK London United Kingdom
Medical Sciences Division University of Oxford Level 3, John Radcliffe Hospital, Oxford OX3 9DU, UK UK United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of Oxford University of Oxford, University Offices, Wellington Square, Oxford, OX1 2JD, UK Oxford United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
Chief Administrative Secretary Rashid Aman Ministry of Health Nairobi Kenya
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator George Warimwe GWarimwe@kemri-wellcome.org +254709983000 KEMRI-Wellcome Trust Research Programme CGMRC, PO Box 230-
City Postal code Country Position/Affiliation
Kilifi 80108 Kenya Principal Investigator
Role Name Email Phone Street address
Scientific Enquiries Philip Bejon pbejon@kemri-wellcome.org +254709983000 KEMRI-Wellcome Trust Research Programme CGMRC, PO Box 230
City Postal code Country Position/Affiliation
Kilifi 80108 Kenya Executive Director
Role Name Email Phone Street address
Public Enquiries Marianne Munene MMunene@kemri-wellcome.org +254709983436 KEMRI-Wellcome Trust Research Programme CGMRC, PO Box 230
City Postal code Country Position/Affiliation
Kilifi 80108 Kenya Research Governance Manager
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual-level anonymized data will be shared with the Sponsor. For wider stakeholder engagement and the medical community, summary-level statistical analyses will be shared. Information collected or generated during this study may be anonymised for use to support new research on coronavirus vaccines and immunology. Any future research using information from this study must first be approved by a local or national expert committee to make sure that the interests of participants and their communities are protected. Data will be managed by KEMRI CGMRC. Analytic Code,Informed Consent Form,Statistical Analysis Plan,Study Protocol At the end of the study (2 years) On completion of the trial and submission of the manuscript. De-identified trial data that underlies the results reported in the publication will be uploaded onto the KWTRP data repository on Harvard Dataverse as per the curation policy. This data will be uploaded under managed access. Requests for access to data will be submitted via email through a form available on the repository and reviewed by the KWTRP Data Governance Committee (DGC) who will also determine whether further approvals are required before data is shared.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://wellcome.ac.uk/grant-funding/guidance/data-software-materials-management-and-sharing-policy No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial phase 04/05/2020 Editing error, trial will start with phase I then progress to phase II. Phase-2 Phase-1
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 04/05/2020 Not changed as the recruitment centre name refers to one site, the KEMRI Wellcome Trust Research Programme is embedded within the Coast Geographic Medicine Research centre. If additional recruiting sites are identified, the record will be updated. KEMRI Wellcome Trust Research Program KWTRP Centre for Geographic Medicine Coast CGMRC, Hospital Grounds, Off Bofa Road, PO Box 230, Kilifi Kenya, 80108, Kenya KEMRI Wellcome Trust Research Programme KWTRP Centre for Geographic Medicine Coast CGMRC, Hospital Grounds, Off Bofa Road, PO Box 230, Kilifi Kenya, 80108, Kenya
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 04/05/2020 This is one center. KEMRI Wellcome Trust Research Programme (KWTRP) is embedded within the Centre for Geographic Medicine Coast (GCMRC). In cases there are other additional centers included, we will update this information. KEMRI Wellcome Trust Research Programme KWTRP Centre for Geographic Medicine Coast CGMRC, Hospital Grounds, Off Bofa Road, PO Box 230, Kilifi Kenya, 80108, Kenya KEMRI Wellcome Trust Research Programme Centre for Geographic Medicine Coast KWTRP CGMRC, Hospital Grounds, Off Bofa Road, PO Box 230, Kilifi Kenya, 80108, Kenya
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 25/05/2020 Updated numbers of COVID-19 cases, and number of participants already vaccinated in the UK. The coronavirus disease (COVID-19) pandemic has so far affected over 3 million people globally, with more than 200,000 deaths. The disease has been reported in over 200 countries, including Kenya where 465 cases had been reported as of 4th May 2020. No vaccines or treatments are currently available for COVID-19. However, there are many COVID-19 vaccine candidates in development, but none of these are in development in Africa and no vaccine trials are currently ongoing in Africa. Vaccine performance from studies in other populations may not be generalizable to Kenya and other African countries. As the number of cases continue to rise globally, an effective vaccine remains the best way to control the pandemic and to safely relax social distancing and other restrictions. A candidate COVID-19 vaccine called ChAdOx1 nCoV-19 has been developed by the University of Oxford, using a platform, termed ‘ChAdOx1’, that is known to be safe in humans based on its use for making vaccines against other diseases. ChAdOx1 nCoV-19 has shown promise in a range of animal models of COVID-19 disease and is currently undergoing clinical trial in humans in the United Kingdom (UK) (ClinicalTrials.gov number: NCT04324606). In this study we plan to evaluate the safety and immunogenicity of ChAdOx1 nCoV-19 vaccine among 400 adults aged ≥18 years. Vaccine efficacy will be evaluated as a secondary objective. The study will take place in the coastal counties of Kilifi and Mombasa, where high numbers of COVID-19 cases have been reported. The study will only enrol healthcare workers (HCWs) including doctors, nurses, clinical officers, pharmacists, mortuary attendants and allied healthcare professionals. HCWs have been prioritised due to their high risk of occupational exposure to COVID-19, hence their urgent need for protection. If found to be safe and effective in generating protective immune responses, the ChAdOx1 nCoV-19 will be further developed for use in controlling COVID-19. The COVID-19 pandemic has so far affected over 5 million people globally, with more than 330,000 deaths. The disease has been reported in over 200 countries, including Kenya where 1214 cases had been reported as of 24th May 2020. No vaccines or treatments are currently available for COVID-19. However, there are many COVID-19 vaccine candidates in development, but none of these are in development in Africa and no vaccine trials are currently ongoing in Africa. Vaccine performance from studies in other populations may not be generalizable to Kenya and other African countries. As the number of cases continue to rise globally, an effective vaccine remains the best way to control the pandemic and to safely relax social distancing and other restrictions. A candidate COVID-19 vaccine called ChAdOx1 nCoV-19 has been developed by the University of Oxford, using a platform, termed ‘ChAdOx1’, that is known to be safe in humans based on its use for making vaccines against other diseases. ChAdOx1 nCoV-19 has shown promise in a range of animal models of COVID-19 disease and is currently undergoing clinical trial in humans in the United Kingdom, where more than 1000 volunteers have been vaccinated (ClinicalTrials.gov no: NCT04324606). In this study we plan to evaluate the safety and immunogenicity of ChAdOx1 nCoV-19 vaccine among 400 adults aged ≥18 years. Vaccine efficacy will be evaluated as a secondary objective. The study will take place in the coastal counties of Kilifi and Mombasa, where high numbers of COVID-19 cases have been reported and will enrol healthcare workers (HCWs) including doctors, nurses, clinical officers, pharmacists, mortuary attendants and allied healthcare professionals. HCWs have been prioritised due to their high risk of occupational exposure to COVID-19, hence their urgent need for protection. If found to be safe and effective in generating protective immune responses, the ChAdOx1 nCoV-19 will be further developed for use in controlling COVID-19.
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 25/05/2020 Updated contact details Principal Investigator, George, Warimwe, Prof., GWarimwe@kemri-wellcome.org, , +254708257982, KEMRI-Wellcome Trust Research Programme CGMRC, PO Box 230-, Kilifi, 80108, Kenya, Principal Investigator Principal Investigator, George, Warimwe, Prof., GWarimwe@kemri-wellcome.org, , +254709983000, KEMRI-Wellcome Trust Research Programme CGMRC, PO Box 230-, Kilifi, 80108, Kenya, Principal Investigator
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Purpose of the trial 25/06/2020 edit Prevention Prevention: Vaccines
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Public title 11/09/2020 Changes have been updated as per the current approved protocol A study to determine if a new COVID-19 vaccine safely generates protective immune responses in adults in Kenya A study to determine if a new vaccine safely generates good immune responses to protect adults in Kenya from Coronavirus Disease
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Official scientific title 11/09/2020 Changes have been updated as per the current approved protocol A phase Ib/II single-blinded, randomised, controlled study to determine safety, immunogenicity and efficacy of the candidate Coronavirus Disease (COVID-19) vaccine ChAdOx1 nCoV-19 in adults in Kenya A phase Ib/II single-blinded, randomised, controlled study to determine safety, immunogenicity and efficacy of the candidate Coronavirus Disease (COVID-19) vaccine ChAdOx1 nCoV-19 in adults in Kenya (COV004)
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 11/09/2020 Changes have been updated as per the current approved protocol The COVID-19 pandemic has so far affected over 5 million people globally, with more than 330,000 deaths. The disease has been reported in over 200 countries, including Kenya where 1214 cases had been reported as of 24th May 2020. No vaccines or treatments are currently available for COVID-19. However, there are many COVID-19 vaccine candidates in development, but none of these are in development in Africa and no vaccine trials are currently ongoing in Africa. Vaccine performance from studies in other populations may not be generalizable to Kenya and other African countries. As the number of cases continue to rise globally, an effective vaccine remains the best way to control the pandemic and to safely relax social distancing and other restrictions. A candidate COVID-19 vaccine called ChAdOx1 nCoV-19 has been developed by the University of Oxford, using a platform, termed ‘ChAdOx1’, that is known to be safe in humans based on its use for making vaccines against other diseases. ChAdOx1 nCoV-19 has shown promise in a range of animal models of COVID-19 disease and is currently undergoing clinical trial in humans in the United Kingdom, where more than 1000 volunteers have been vaccinated (ClinicalTrials.gov no: NCT04324606). In this study we plan to evaluate the safety and immunogenicity of ChAdOx1 nCoV-19 vaccine among 400 adults aged ≥18 years. Vaccine efficacy will be evaluated as a secondary objective. The study will take place in the coastal counties of Kilifi and Mombasa, where high numbers of COVID-19 cases have been reported and will enrol healthcare workers (HCWs) including doctors, nurses, clinical officers, pharmacists, mortuary attendants and allied healthcare professionals. HCWs have been prioritised due to their high risk of occupational exposure to COVID-19, hence their urgent need for protection. If found to be safe and effective in generating protective immune responses, the ChAdOx1 nCoV-19 will be further developed for use in controlling COVID-19. As of 4th August 2020, the coronavirus disease (COVID-19) pandemic has affected over 18 million people globally, with close to 700,000 deaths. The disease has been reported in over 200 countries, including Kenya where over 23,000 cases have been reported. No vaccines or treatments are currently licensed for use against COVID-19. As the number of cases continue to rise globally, an effective vaccine remains the best way to control the pandemic and to safely relax physical distancing and other restrictions. There are over 150 COVID-19 vaccine candidates in development, with 26 of these currently undergoing evaluation in human clinical trials (as of 4th August 2020). Of the 26 vaccines, ChAdOx1 nCoV-19, a candidate vaccine developed by our longstanding collaborators at the University of Oxford in partnership with AstraZeneca, is the most advanced. ChAdOx1 nCoV-19 has shown promise in a range of animal models of COVID-19 disease and has already been administered to over 5,000 adult volunteers in the United Kingdom, Brazil and South Africa (Registration numbers: NCT04324606, NCT04400838, ISRCTN89951424 and NCT04444674). In this single-blinded randomized study we plan to evaluate the safety and immunogenicity of a single dose of ChAdOx1 nCoV-19 (5x1010 vp) vaccine among 400 adults aged ≥18 years. The study will take place in the coastal counties of Kilifi and Mombasa, where high numbers of COVID-19 cases have been detected. The study will only enrol frontline staff as defined by the government. These populations have been prioritised due to their high risk of occupational exposure to COVID-19, hence their urgent need for protection. Participants will be randomized to receive either ChAdOx1 nCoV-19 (n=200) or rabies vaccine (n=200). Out of these, 40 will be enrolled in the phase Ib trial, and the remainder to the phase II trial (180 per vaccine). After vaccination, they will be required to complete diary cards (paper or electronic) and record any solicited and unsolicited adverse events experienced for 6 days following vaccination while at home. Each participant will have 7 clinic visits in the course of the study and some of the activities that will be carried out will include; physical assessment, checking vital signs, phlebotomy and safety assessment. If found to be safe and effective in generating protective immune responses, the ChAdOx1 nCoV-19 will be further developed for use in controlling COVID-19, including in populations in Kenya and other countries in Africa.
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Acronym 11/09/2020 Changes have been updated as per the current approved protocol COV004
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated trial start date 11/09/2020 Changes have been updated as per the current timelines 31 May 2020 01 Oct 2020
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated date of last follow up 11/09/2020 Changes have been updated as per the current timelines 31 May 2022 01 Oct 2022
Section Name Field Name Date Reason Old Value Updated Value
Study Design Masking / blinding 11/09/2020 Changes have been updated as per the current approved protocol. Participants Outcome Assessors, Care giver/Provider, Participants
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Inclusion criteria 11/09/2020 Details updated as per the current approved protocol • Healthy adults aged 18-55 years for phase Ib, ≥18 years for phase II. • Able and willing (in the Investigators’ opinion) to comply with all study requirements, including making visits to KEMRI CGMRC or other designated study health facility for follow up under conditions with limited transport. • Agreement to refrain from blood donation during the course of the study • Use of effective method of contraception for duration of study for female participants. They should use effective contraception for 30 days prior to vaccination. For female participants, we will ask them to attend with their family planning records for verification. Effective contraception is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly, in accordance with the product label. Examples of these include: combined oral contraceptives; injectable progestogen; implants of etenogestrel or levonorgestrel; intrauterine device or intrauterine system; male partner sterilisation at least 6 months prior to the female subject’s entry into the study, and the relationship is monogamous; male condom combined with a vaginal spermicide (foam, gel, film, cream or suppository); and male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository). • Provide written informed consent. • Plan to remain resident in the study area for 1 year following vaccination • Frontline Staff as defined by the Government of Kenya • Healthy adults aged 18-55 years for phase Ib, ≥18 years for phase II. • Able and willing (in the Investigators’ opinion) to comply with all study requirements, including making visits to KEMRI CGMRC or other designated study health facility for follow up under conditions with limited transport. • Agreement to refrain from blood donation during the course of the study • Use of effective method of contraception for duration of study for female participants. They should use effective contraception for 30 days prior to vaccination. For female participants, we will ask them to attend with their family planning records for verification. Effective contraception is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly, in accordance with the product label. Examples of these include: combined oral contraceptives; injectable progestogen; implants of etenogestrel or levonorgestrel; intrauterine device or intrauterine system; male partner sterilisation at least 6 months prior to the female subject’s entry into the study, and the relationship is monogamous; male condom combined with a vaginal spermicide (foam, gel, film, cream or suppository); and male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository). • Provide written informed consent. • Plan to remain resident in the study area for 1 year following vaccination
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Exclusion criteria 11/09/2020 Details updated as per the current approved protocol • Prior receipt of any vaccines (licensed or investigational) ≤30 days before enrolment • Planned receipt of any vaccine other than the study intervention within 30 days before or after study vaccination. • Prior receipt of an investigational or licensed vaccine likely to impact on interpretation of the trial data (e.g. Adenovirus vectored vaccines, any coronavirus vaccines). • Planned or ongoing participation in any other interventional studies (of licensed or investigational products) ≤30 days before enrolment and for the duration of the study. • Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate. • Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection (HIV will be an exclusion only for the phase 1b); asplenia; recurrent severe infections and chronic use (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed). NB: HIV+ participants with a CD4 count >200 within the last 6 months, and no symptoms suggestive of current clinical immunosuppression will be eligible for inclusion in the phase II trial. • History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. • Any history of hereditary or idiopathic angioedema. • Pregnancy, lactation or willingness/intention to become pregnant during the study. • History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ). • History of serious psychiatric condition likely to affect participation in the study. • Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture. • Any other serious chronic illness requiring hospital specialist supervision. • Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week. • Suspected or known injecting drug abuse in the 5 years preceding enrolment. • Any clinically significant abnormal finding on screening biochemistry, haematology blood tests or urinalysis. • Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data. • History of laboratory-confirmed COVID-19 or SARS-CoV-2 infection. • New onset of fever and a cough or shortness of breath in the 30 days preceding screening and/or enrolment. • Prior receipt of any vaccines (licensed or investigational) ≤30 days before enrolment • Volunteer who is not literate. • Planned receipt of any vaccine other than the study intervention within 30 days before or after study vaccination. • Prior receipt of an investigational or licensed vaccine likely to impact on interpretation of the trial data (e.g. Adenovirus vectored vaccines, any coronavirus vaccines). • Planned or ongoing participation in any other interventional studies (of licensed or investigational products) ≤30 days before enrolment and for the duration of the study. • Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate. • Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent severe infections and chronic use (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed). • History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. • Any history of hereditary or idiopathic angioedema. • Pregnancy, lactation or willingness/intention to become pregnant during the study. • History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ). • History of serious psychiatric condition likely to affect participation in the study. • Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture. • Any other serious chronic illness requiring hospital specialist supervision. • Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week (e.g. more than 2 bottles of 500mls Tusker (beer) a day, more than 2 large glasses of 12% wine per day)
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 11/09/2020 Updated according to the current approved protocol Primary Outcome, 1. Occurrence of serious adverse events (SAEs) throughout the study duration 2. ELISA to quantify IgG antibodies against SARS- CoV-2 spike protein, 1- Throughout the study, 2- Days 0, 14, 28, 84, 182 and 365 Primary Outcome, 1. Occurrence of serious adverse events (SAEs) throughout the study duration 2. Occurrence of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination 3. Occurrence of unsolicited adverse events (AEs) at all scheduled visits; 4. Change from baseline for safety laboratory measures and; 5. Occurrence of SAE of special interest: disease enhancement episodes , 1- Throughout the study, 2- Days 0 to 7, 3 and 5-Throughout the study, 4-day 7 and 28
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 11/09/2020 Detailed updated according to the current protocol Primary Outcome, 1. Occurrence of serious adverse events (SAEs) throughout the study duration 2. Occurrence of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination 3. Occurrence of unsolicited adverse events (AEs) at all scheduled visits; 4. Change from baseline for safety laboratory measures and; 5. Occurrence of SAE of special interest: disease enhancement episodes , 1- Throughout the study, 2- Days 0 to 7, 3 and 5-Throughout the study, 4-day 7 and 28 Primary Outcome, A. To assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1nCoV-19 1. Occurrence of serious adverse events (SAEs) throughout the study duration 2. Occurrence of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination 3. Occurrence of unsolicited adverse events (AEs) at all scheduled visits; 4. Change from baseline for safety laboratory measures and; 5. Occurrence of SAE of special interest: disease enhancement episodes B. To assess immunogenicity of ChAdOx1 nCoV-19 1. ELISA to quantify IgG antibodies against SARSCoV-2 spike protein (seroconversion rates), A1- Throughout the study, 2- Days 0 to 7, 3 and 5-Throughout the study, 4-day 7 and 28, B1-day 0 and 28
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 11/09/2020 Details updated as per the current approved protocol Primary Outcome, A. To assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1nCoV-19 1. Occurrence of serious adverse events (SAEs) throughout the study duration 2. Occurrence of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination 3. Occurrence of unsolicited adverse events (AEs) at all scheduled visits; 4. Change from baseline for safety laboratory measures and; 5. Occurrence of SAE of special interest: disease enhancement episodes B. To assess immunogenicity of ChAdOx1 nCoV-19 1. ELISA to quantify IgG antibodies against SARSCoV-2 spike protein (seroconversion rates), A1- Throughout the study, 2- Days 0 to 7, 3 and 5-Throughout the study, 4-day 7 and 28, B1-day 0 and 28 Primary Outcome, A. To assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1nCoV-19 1. Occurrence of serious adverse events (SAEs) throughout the study duration 2. Occurrence of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination 3. Occurrence of unsolicited adverse events (AEs) at all scheduled visits; 4. Change from baseline for safety laboratory measures and; 5. Occurrence of SAE of special interest: disease enhancement episodes B. To assess immunogenicity of ChAdOx1 nCoV-19 1. ELISA to quantify IgG antibodies against SARSCoV-2 spike protein (seroconversion rates), A1- Throughout the study, A2- Days 0 to 7, A3 and A5-Throughout the study, A4-day 7 and 28, B1-day 0 and 28
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 11/09/2020 Updated as per the current approved protocol Secondary Outcome, 1. IFN-γ ELISpot responses to SARS-CoV-2 spike protein; 2. a. Occurrence of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination b. Occurrence of unsolicited adverse events (AEs) for 28 days following vaccination; c. Change from baseline for safety laboratory measures and; d. Occurrence of SAE of special interest: disease enhancement episodes 3. a.Virologically confirmed (PCR positive) symptomatic cases of COVID-19 b. Hospital admissions associated with COVID-19 c. Deaths associated with COVID-19 d. Seroconversion against non-Spike antigens measured by ELISA e. Asymptomatic SARS-CoV-2 carriage, 1: days 0, 14, 28, 84, 182 and 365. 2a: day 0-7. 2b- days 0-28. 2c: baseline, days 0 and 28. 2d to 3c: Throughout the study. 3d and 3e: days 0, 14, 28, 84, 182 and 365. Secondary Outcome, A. To assess humoral immunogenicity of ChAdOx1 nCoV-19 at early and late timepoints 1. ELISA to quantify IgG antibodies against SARS-CoV-2 spike protein (seroconversion rates) B. To assess cellular immunogenicity of ChAdOx1 nCoV-19 1. IFN-γ ELISpot responses to SARS-CoV-2 spike protein; C. To assess efficacy of ChAdOx1 nCoV-19 against COVID-19 1. Virologically confirmed (PCR positive) symptomatic cases of COVID-19 2. Hospital admissions associated with COVID-19 3. Deaths associated with COVID-19 4. Seroconversion against non-Spike antigens measured by ELISA 5. Asymptomatic SARS-CoV2 carriage , day 0,14, 84 182, 365
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 11/09/2020 We now have the IRB approval attached FALSE, KEMRI Scientific and Ethics Review Unit, Kenya Medical Research Institute, Off Mbagathi Way Nairobi. Postal address P.O. BOX 54840, Nairobi, 00200, Kenya, 04 May 2020, , +254202726781, seru@kemri.org, FALSE, KEMRI Scientific and Ethics Review Unit, Kenya Medical Research Institute, Off Mbagathi Way Nairobi. Postal address P.O. BOX 54840, Nairobi, 00200, Kenya, 04 May 2020, , +254202726781, seru@kemri.org, 10988_11282_4737.pdf
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Funding Source FundingSources List 11/09/2020 Updated funding details Medical Sciences Division University of Oxford, Level 3, John Radcliffe Hospital, Oxford OX3 9DU, UK, UK, , United Kingdom, Other Collaborative Groups,
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Trial Information Official scientific title 11/09/2020 Correction of typo A phase Ib/II single-blinded, randomised, controlled study to determine safety, immunogenicity and efficacy of the candidate Coronavirus Disease (COVID-19) vaccine ChAdOx1 nCoV-19 in adults in Kenya (COV004) A phase Ib/II single-blinded, randomised, controlled study to determine safety, immunogenicity and efficacy of the candidate Coronavirus Disease (COVID-19) vaccine ChAdOx1 nCoV-19 in adults in Kenya (COV004)
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 11/09/2020 Update to background info & study population As of 4th August 2020, the coronavirus disease (COVID-19) pandemic has affected over 18 million people globally, with close to 700,000 deaths. The disease has been reported in over 200 countries, including Kenya where over 23,000 cases have been reported. No vaccines or treatments are currently licensed for use against COVID-19. As the number of cases continue to rise globally, an effective vaccine remains the best way to control the pandemic and to safely relax physical distancing and other restrictions. There are over 150 COVID-19 vaccine candidates in development, with 26 of these currently undergoing evaluation in human clinical trials (as of 4th August 2020). Of the 26 vaccines, ChAdOx1 nCoV-19, a candidate vaccine developed by our longstanding collaborators at the University of Oxford in partnership with AstraZeneca, is the most advanced. ChAdOx1 nCoV-19 has shown promise in a range of animal models of COVID-19 disease and has already been administered to over 5,000 adult volunteers in the United Kingdom, Brazil and South Africa (Registration numbers: NCT04324606, NCT04400838, ISRCTN89951424 and NCT04444674). In this single-blinded randomized study we plan to evaluate the safety and immunogenicity of a single dose of ChAdOx1 nCoV-19 (5x1010 vp) vaccine among 400 adults aged ≥18 years. The study will take place in the coastal counties of Kilifi and Mombasa, where high numbers of COVID-19 cases have been detected. The study will only enrol frontline staff as defined by the government. These populations have been prioritised due to their high risk of occupational exposure to COVID-19, hence their urgent need for protection. Participants will be randomized to receive either ChAdOx1 nCoV-19 (n=200) or rabies vaccine (n=200). Out of these, 40 will be enrolled in the phase Ib trial, and the remainder to the phase II trial (180 per vaccine). After vaccination, they will be required to complete diary cards (paper or electronic) and record any solicited and unsolicited adverse events experienced for 6 days following vaccination while at home. Each participant will have 7 clinic visits in the course of the study and some of the activities that will be carried out will include; physical assessment, checking vital signs, phlebotomy and safety assessment. If found to be safe and effective in generating protective immune responses, the ChAdOx1 nCoV-19 will be further developed for use in controlling COVID-19, including in populations in Kenya and other countries in Africa. As of 11th September 2020, the COVID-19 pandemic has affected over 27 million people globally, with over 900,000 deaths. The disease has been reported in over 200 countries, including Kenya where over 35,000 cases have been reported. No vaccines or treatments are currently licensed for use against COVID-19. As the number of cases continue to rise globally, an effective vaccine remains the best way to control the pandemic and to safely relax physical distancing and other restrictions. There are over 30 COVID-19 vaccine candidates in clinical development. ChAdOx1 nCoV-19, developed by the University of Oxford in partnership with AstraZeneca, is the most advanced. ChAdOx1 nCoV-19 has shown promise in a range of animal models of COVID-19 disease and has already been administered to over 5,000 adult volunteers in the United Kingdom, Brazil and South Africa (Registration numbers: NCT04324606, NCT04400838, ISRCTN89951424 and NCT04444674). We plan to evaluate the safety and immunogenicity of a single dose of ChAdOx1 nCoV-19 (5x1010 vp) vaccine among 400 adults aged ≥18 years. The study will take place in the coastal counties of Kilifi and Mombasa, where high numbers of COVID-19 cases have been detected. The study will only enrol frontline workers in key service areas e.g. healthcare workers, allied health professionals, truckers, among others. These populations have been prioritised due to their high risk of occupational exposure to COVID-19, hence their urgent need for protection. Participants will be randomized to receive either ChAdOx1 nCoV-19 (n=200) or rabies vaccine (n=200). Out of these, 40 will be enrolled in the phase Ib trial, and the remainder to the phase II trial (180 per vaccine). If found to be safe and effective in generating protective immune responses, the ChAdOx1 nCoV-19 will be further developed for use in controlling COVID-19, including in populations in Kenya and other countries in Africa.
Section Name Field Name Date Reason Old Value Updated Value
Collaborators Collaborators List 11/09/2020 Addition of Collaborator Chief Administrative Secretary Rashid Aman , Ministry of Health, Nairobi, , Kenya
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 11/09/2020 Update to background info & study population As of 11th September 2020, the COVID-19 pandemic has affected over 27 million people globally, with over 900,000 deaths. The disease has been reported in over 200 countries, including Kenya where over 35,000 cases have been reported. No vaccines or treatments are currently licensed for use against COVID-19. As the number of cases continue to rise globally, an effective vaccine remains the best way to control the pandemic and to safely relax physical distancing and other restrictions. There are over 30 COVID-19 vaccine candidates in clinical development. ChAdOx1 nCoV-19, developed by the University of Oxford in partnership with AstraZeneca, is the most advanced. ChAdOx1 nCoV-19 has shown promise in a range of animal models of COVID-19 disease and has already been administered to over 5,000 adult volunteers in the United Kingdom, Brazil and South Africa (Registration numbers: NCT04324606, NCT04400838, ISRCTN89951424 and NCT04444674). We plan to evaluate the safety and immunogenicity of a single dose of ChAdOx1 nCoV-19 (5x1010 vp) vaccine among 400 adults aged ≥18 years. The study will take place in the coastal counties of Kilifi and Mombasa, where high numbers of COVID-19 cases have been detected. The study will only enrol frontline workers in key service areas e.g. healthcare workers, allied health professionals, truckers, among others. These populations have been prioritised due to their high risk of occupational exposure to COVID-19, hence their urgent need for protection. Participants will be randomized to receive either ChAdOx1 nCoV-19 (n=200) or rabies vaccine (n=200). Out of these, 40 will be enrolled in the phase Ib trial, and the remainder to the phase II trial (180 per vaccine). If found to be safe and effective in generating protective immune responses, the ChAdOx1 nCoV-19 will be further developed for use in controlling COVID-19, including in populations in Kenya and other countries in Africa. As of 11th September 2020, the COVID-19 pandemic has affected over 27 million people globally, with over 900,000 deaths. The disease has been reported in over 200 countries, including Kenya where over 35,000 cases have been reported. No vaccines or treatments are currently licensed for use against COVID-19. As the number of cases continue to rise globally, an effective vaccine remains the best way to control the pandemic and to safely relax physical distancing and other restrictions. There are over 30 COVID-19 vaccine candidates in clinical development. ChAdOx1 nCoV-19, developed by the University of Oxford in partnership with AstraZeneca, is the most advanced. ChAdOx1 nCoV-19 has shown promise in a range of animal models of COVID-19 disease and has already been administered to over 5,000 adult volunteers in the United Kingdom, Brazil and South Africa (Registration numbers: NCT04324606, NCT04400838, ISRCTN89951424 and NCT04444674). We plan to evaluate the safety and immunogenicity of a single dose of ChAdOx1 nCoV-19 (5x1010 vp) vaccine among 400 adults aged ≥18 years. The study will take place in the coastal counties of Kilifi and Mombasa, where high numbers of COVID-19 cases have been detected. The study will only enrol frontline workers in key service areas e.g. healthcare workers, allied health professionals, truckers, among others. These populations have been prioritised due to their high risk of occupational exposure to COVID-19, hence their urgent need for protection. Participants will be randomized to receive either ChAdOx1 nCoV-19 (n=200) or rabies vaccine (n=200). Out of these, 40 will be enrolled in the phase Ib trial, and the remainder to the phase II trial (180 per vaccine). If found to be safe and effective in generating protective immune responses, the ChAdOx1 nCoV-19 will be further developed for use in controlling COVID-19, including in populations in Kenya and other countries in Africa.