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: pactr.samrc.ac.za
Trial no.: PACTR202108616900606 Date of Approval: 26/08/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A Partially-Blinded, Randomized, Phase 3 Study to Evaluate the Immunogenicity and Safety of CpG/Alum-adjuvanted Recombinant SARS-CoV-2 Trimeric S-protein Subunit Vaccine (SCB-2019) in Healthy Adults and Individuals with HIV Infection
Official scientific title Phase 3 Study of Immunogenicity and Safety of Adjuvanted SARS-CoV-2 (SCB 2019) Vaccine in Healthy Adults and Individuals with HIV Infection
Brief summary describing the background and objectives of the trial The severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection leads to a cluster of respiratory illnesses, collectively called COVID-19, similar to those caused by SARS-CoV. COVID-19 has been associated with a high transmission rate, and severe cases require admission to hospital intensive care units with the need for mechanical ventilation and associated high mortality. International health authorities suggest that individuals aged 65 years and above and people with underlying comorbidities such as hypertension, chronic lung disease, cardiovascular disease, cancer, diabetes, and immunosuppressed medical conditions, including HIV infection, are at increased risk of severe COVID-19. Persons living with diagnosed HIV experienced poorer COVID-related outcomes relative to persons living without diagnosed HIV; previous HIV diagnosis was associated with higher rates of severe disease requiring hospitalization, and hospitalization risk increased with progression of HIV disease stage. The authorized or licensed vaccines and most vaccine candidates in development are focused on the major antigenic target of the virus, the SARS-CoV-2 Spike (S) protein. SCB-2019 is a recombinant SARS-CoV-2 S-Trimer protein fused to Trimer-Tag© produced in Chinese hamster ovary cells. Trimer-Tag© is derived from the fully-human C-propeptide domain of pro-collagen. Immunogenicity and safety of different dose levels (3, 9, and 30 µg) of SCB-2019 vaccine, administered standalone and with CpG 1018 and Aluminum hydroxide (CpG/Alum) and AS03 adjuvant systems were assessed in Phase 1 clinical study. All tested formulations were well-tolerated and induced neutralizing antibodies against Spike protein of the SARS-CoV-2 virus. A 30 µg of SCB-2019 with CpG/Alum adjuvant was selected for further evaluation in the Phase 3 program as having a favorable benefit/risk profile. The ongoing pivotal Phase 3 efficacy and safety clinical study (CLO-SCB-2019-003) has recruited at least 26,000 healthy adolescent and adult participants and individuals with stable pre-existing stable chronic medical conditions, including HIV infection. However, this study does not explicitly describe the immunogenicity, reactogenicity and safety in participants with HIV infection. HIV infection is known to impact immune response to several vaccines. However, use of ART treatment in this population allowed to achieve adequate and protective immune responses to many vaccines. This includes vaccines using a toll-like receptor-9 (TLR-9) agonist as adjuvant which are known to have a potential impact on HIV infection parameters (e.g. CD4+ T-cell count, ribonucleic acid [RNA] viral load). In addition, recent data on authorized or licensed SARS-CoV-2 vaccines indicates that extending the interval between the first and second dose is associated with a higher vaccine efficacy. In the current pandemic situation where access to doses is under pressure, flexibility regarding the interval between doses is important. The summarized objectives of this study are: to describe immunogenicity, reactogenicity and safety of the SCB-2019 vaccine in both participants with HIV infection and healthy participants, who received 2-dose vaccination series 3 or 6 weeks apart, in terms of SARS-CoV-2 neutralizing titers, 21 days after second vaccination with SCB-2019. In HIV infected subjects, immunogenicity will also be analyzed by baseline CD4+ T-cell count and RNA viral load. In addition, changes in CD4+ T-cell count and HIV RNA viral load compared to baseline are also to be evaluated.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) CLOSCB2019004
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied severe acute respiratory syndrome coronavirus 2 SARS CoV 2
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 15/08/2021
Actual trial start date
Anticipated date of last follow up 30/04/2022
Actual Last follow-up date
Anticipated target sample size (number of participants) 600
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
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Simple randomization using a randomization table created by a computer software program Numbered containers Masking/blinding used Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group placebo 0.5 ml For each participant, the study duration will be approximately 7-8 months (approximately 6 months after the last study vaccination). Saline solution (0.9%) 300 Placebo
Experimental Group CpG 1018 alumadjuvanted SCB2019 vaccine 0.5 mL (SCB-2019 adjuvanted with CpG 1018 plus Alum Alhydrogel) For each participant, the study duration will be approximately 7-8 months (approximately 6 months after the last study vaccination). "SCB-2019: prefilled syringe (720 µg in 1.0 mL) for preparation of 20 doses of study vaccine. CpG 1018 Adjuvant: a vial (2.0 mL) containing 12 mg/mL of a 22-mer phosphorothioate oligodeoxynucleotide in Tris buffered saline (24 mg per vial). Alhydrogel: a vial (1.8 mL) containing 10 mg/mL of aluminum hydroxide." 300
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Male or female ≥18 years of age. 2. Individuals or their witnesses in case of illiteracy are willing and able to comply with study requirements, including all scheduled visits, vaccinations, laboratory tests, and other study procedures. 3. Individuals are willing and able to give an informed consent, prior to screening. 4. Female participants of childbearing potential may be enrolled in the study if the participant has practiced adequate contraception using a highly effective licensed method of birth control for 30 days prior to the first vaccination and has a negative pregnancy test on the day of vaccination and must agree to continue such precautions during until 90 days after the last vaccination. 5. Male participants must agree to employ acceptable contraception from the day of first dose of the study vaccine/comparator until 6 months after the first dose of the study vaccine/comparator and refrain from donating sperm during this period. 6. For HIV infected participants: individuals should be in general good health except stable HIV infection receiving a stable ART treatment for at least 6 months (defined as no change because of virological or immunological failure) and to have a CD4+ T-cell count > 200 cells/mm3 and a HIV RNA load of ≤50 copies/mL at screening. 1. Individuals with fever >37.5°C (irrespective of method), or any acute illness at baseline (Day 1) or within 3 days prior to randomization. Participants meeting this criterion may be rescheduled within the relevant window. Afebrile participants with minor illnesses can be enrolled at the discretion of the investigator. 2. Individuals with laboratory-confirmed SARS-CoV-2 infection (as defined by Rapid COVID Antigen Test or an equivalent at Visit 1) or with history of COVID-19. 3. Individuals who have received a prior investigational or authorized or licensed COVID-19 vaccine. 4. Any confirmed or suspected immunosuppressive or immunodeficient condition except HIV infection resulting from disease or immunosuppressive/cytotoxic therapy (e.g., medications used for cancer chemotherapy, organ transplantation or to treat autoimmune disorders) within 6 months prior to enrollment. 5. Individuals who have a history of malignancy within 1 year before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix which have been cured, or other malignancies with minimal risk of recurrence). 6. Individuals with any progressive unstable or uncontrolled clinical conditions. 7. Individuals who are pregnant, or breastfeeding, or planning to become pregnant while enrolled in this study or within 3 months after the last study vaccination. 8. Individuals who have a history of severe adverse reaction associated with a vaccine or severe allergic reaction (e.g., anaphylaxis) to any component of the study vaccines (CpG/Alum/SCB-2019 components as outlined in the latest IB). 9. Individuals who have received any other investigational product within 30 days prior to Day 1 or intend to participate in another clinical study at any time during the conduct of this study. 10. Individuals who have received any other authorized or licensed vaccines within 14 days prior to enrollment in this study or who are planning to receive any vaccine up to 21 days after the last vaccination. 11. Individuals with known bleeding disorder that would, in the opinion of the investigator, contraindicate intramuscular injection. 12. Individuals who have received treatment with rituximab or any other anti-CD20 monoclonal antibodies within 9 months prior to enrollment or planned during the study period. 13. Individuals who have received intravenous immunoglobulins and/or any blood products within 3 months prior to enrollment or planned administration during the study period. 14. Individuals with any condition that, in the opinion of the investigator, would interfere with the primary study objectives or pose additional participant risk. 80 and over: 80+ Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 80 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 08/08/2021 KENYA MEDICAL RESEARCH INSTITUTE Scientific Ethics Review Unit KEMRISERU
Ethics Committee Address
Street address City Postal code Country
Mbagathi Road NAIROBI PO BOX 54 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Secondary Outcome -To describe immunogenicity of the SCB-2019 vaccine in both participants with HIV infection and healthy participants, who received 2-dose vaccination series 3 or 6 weeks apart, in terms of SARS-CoV-2 neutralizing titers and antibodies specific to SCB-2019 antigen -To describe immunogenicity of the SCB-2019 vaccine in participants with HIV infection, who received 2-dose vaccination series 3 or 6 weeks apart, by baseline CD4+ T-cell count and RNA viral load -To describe changes in CD4+ T-cell count and HIV RNA viral load compared to baseline Please refer to the above section
Primary Outcome To describe immunogenicity of the SCB-2019 vaccine in both participants with HIV infection and healthy participants, who received 2-dose vaccination series 3 or 6 weeks apart, in terms of SARS-CoV-2 neutralizing titers, 21 days after second vaccination with SCB-2019. Please refer to the above section
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
CREATES Homabay County Referral Hospital Hospital Road Homabay County 40300 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
Clover Biopharmaceuticals AUS Pty Ltd Level 17 HWT Tower 40 City Road Southbank VIC 3006 Australia
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Clover Biopharmaceuticals AUS Pty Ltd Level 17, HWT Tower, 40 City Road Southbank VIC 3006 Australia Pharmaceutical company
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Bernhards Ogutu ogutu6@gmail.com +254733812613 Hospital Road
City Postal code Country Position/Affiliation
Homabay County Kenya Principal investigator
Role Name Email Phone Street address
Public Enquiries Allan Otieno gaotieno@gmail.com +254733893481 PO Box 54 40100
City Postal code Country Position/Affiliation
Kisumu Kenya KEMIRI Kondele children Hospital
Role Name Email Phone Street address
Scientific Enquiries Hella Ghorbel hella.ghorbel@mct-cro.com 21628881436 4,Avenue de la livre Sterling Les Berges du Lac 2
City Postal code Country Position/Affiliation
Tunis Tunisia Regulatory Manager
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Data dictionaries and all collected IPD will be stripped of identifiers and may be made available upon request Informed Consent Form,Statistical Analysis Plan,Study Protocol upon request NA
URL Results Available Results Summary Result Posting Date First Journal Publication Date
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