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.: PACTR202206754734018 Date of Approval: 01/06/2022
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Safety & Immunogenicity of Fractional Doses of Vaccines Among Nigerian Adults- A Randomised Non-Inferiority Triple Blind Trial
Official scientific title Safety & Immunogenicity of Fractional Doses of Pfizer, AstraZeneca, and Janssen Covid-19 Vaccines Among Nigerian Adults- A Randomised Non-Inferiority Triple Blind Trial
Brief summary describing the background and objectives of the trial The COVID-19 pandemic poses a major public health challenge with varying devastating effects on the global community. It has stretched the fragile health system in some countries and contributed to increased poverty and misery of the world's poor population due to the economic loss resulting from its control efforts and the catastrophic spending on health care. In an effort to curtail this pandemic, several measures have been enacted, ranging from handwashing, use of facemask, social distancing, lockdown, and vaccination with variable outcomes. However, the most effective public health measure at combating the disease is vaccination. Despite improved measures at the delivery of vaccines to Nigeria via COVID-19 Vaccines Global Access (COVAX), the rate of vaccine coverage could be improved via the use of vaccine supplies more efficiently. One of such ways of efficient vaccine use is the concept of fractional dosing of vaccines which could be almost as effective as currently used doses with the possibility of reduced side effects. Fractional dosing is an option with plausible success as evidenced by the WHO measure at successfully combating the Yellow fever epidemics using one-fifth dose of the standard dose in 2016-2018 (WHO, 2017). With a large population size of over 200 million inhabitants, Nigeria could benefit immensely from the fractional dosing of the COVD-I9-vaccines by enhancing immunization coverage, reducing adverse events, increasing vaccine acceptance and helping to save funds for other public health measures of importance. This study aims to evaluate the immunogenicity of fractional dosing of the Moderna, AstraZeneca and Johnson &Johnson vaccines at 25%, 50% to the 100% standard doses and evaluate their safety and tolerability among Nigerians aged 18 - 65.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) SIFCoVAN
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied COVID -19
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 30/05/2022
Actual trial start date 21/06/2022
Anticipated date of last follow up 29/04/2023
Actual Last follow-up date 01/04/2024
Anticipated target sample size (number of participants) 1812
Actual target sample size (number of participants) 1894
Recruitment status Completed
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 Central randomisation by phone/fax 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 Fractional COVID 19 vaccines AstraZeneca COVID-19 vaccine • Standard dosing interval ( 6 weeks between 1st and 2nd dose) o Group A1: 1.25 x 1010 viral particle o Group A2: 2.5 x 1010 viral particle • Extended dosing interval ( 20 weeks between 1st and 2nd dose) o Group A4: 1.25 x 1010 viral particle o Group A5: 2.5 x 1010 viral particle o Group A6: 5.0 x 1010 viral particle Janssen COVID-19 Vaccine • Standard dosing interval ( 12 weeks between 1st and 2nd dose) o Group B1: 1.25 x 1010 viral particle o Group B2: 2.5 x 1010 viral particle • Extended dosing interval ( 24 weeks between 1st and 2nd dose) o Group B4: 1.25 x 1010 viral particle o Group B5: 2.5 x 1010 viral particle o Group B6: 5.0 x 1010 viral particle Pfizer BioNTech COVID-19 vaccine • Standard dosing interval ( 6 weeks between 1st and 2nd dose) o Group C1: 15ug • Extended dosing interval ( 20 weeks between 1st and 2nd dose) o Group C3: 30ug Group A • Standard dosing interval ( 6 weeks between 1st and 2nd dose):Group A1-2) • Extended dosing interval ( 20 weeks between 1st and 2nd dose):Group A4-6) Group B • Standard dosing interval ( 12 weeks between 1st and 2nd dose): Group B1-2) • Extended dosing interval ( 24 weeks between 1st and 2nd dose):Group B4-6) Group C • Standard dosing interval ( 6 weeks between 1st and 2nd dose): Group C1-2) • Extended dosing interval ( 20 weeks between 1st and 2nd dose):Group C3) A multicenter double-blinded, randomized trial of fractional doses of AstraZeneca, Pfizer, and Janseen COVID-19 vaccines at the standard dosage schedules and at extended schedules . Eligible participants will be randomised into three groups with 17 arms (14 arms of experimental groups). The volunteers in Group A (Arms A1, A2, A4, A5, A6) will receive two doses of AstraZeneca COVID – 19 vaccines. While Arms A1 and A2 will receive 1.25 X1010 , and 2.5 X1010 viral particles respectively at the standard dosing interval of 6 weeks between first and second doses, the Arms A4, A5 and A6 will receive 1.25 X1010 , 2.5 X1010 and 5.0 X 1010 viral particles respectively at an extended dosing interval of 20 weeks between first and second doses The volunteers in Group B (Arms B1, B2, B4, B5, B6) will receive two doses of Janssen COVID – 19 vaccines. While Arms B1 and B2 will receive 1.25 X1010 ,and 2.5 X1010 viral particles respectively at the standard dosing interval of 12 weeks between first and second doses, the Arms B4, B5 and B6 will receive 1.25 X1010 , 2.5 X1010 and 5.0 X 1010 viral particles respectively at an extended dosing interval of 24 weeks between first and second doses The volunteers in Group C - Arms C1, C2, and C3 will receive two doses of Pfizer COVID vaccines respectively. Arms C1 and C2 will receive 15ug and 30 ug respectively at the standard dosing interval of 6 weeks between first and second doses. Arms C3 will receive 30ug at the extended dosing interval of 20 weeks between first and second doses. 1308
Control Group Standard COVID 19 vaccines Group A3 : Two doses of 5.0 x 1010 viral particle AstraZeneca COVID-19 vaccine 6 weeks apart •Group B3: Two doses of 5.0 x 1010 viral particle Janssen COVID-19 Vaccine 12 weeks apart •Group C2: Single dose 30ug Pfizer BioNTech COVID-19 vaccine Group A3 - 6 weeks between 1st and 2nd dose Group B3 - 12 weeks between 1st and 2nd dose Group C2 - 6 weeks between 1st and 2nd dose A multicenter double-blinded, randomized trial of fractional doses of AstraZeneca, Pfizer, and Janseen COVID-19 vaccines at the standard dosage schedules and at extended schedules . Eligible participants will be randomised into three groups with 17 arms (three of which are control arms). The volunteers in Group A3 will receive two doses of AstraZeneca COVID Vaccine (5.0 X 1010 viral particles) at the standard dosing interval of 6 weeks between first and second doses. The volunteers in Group B3 will receive two doses of Janssen COVID – 19 vaccines(5.0 X 1010 viral particles) at the standard dosing interval of 12 weeks between first and second doses. . The volunteers in Group C2 will receive the standard dosing (30ug) interval of 6 weeks between first and second doses. 504 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Healthy based on medical examination/history at the inclusion Age 18-65 years Signed informed consent Prepared to grant authorized persons access to the medical records The volunteer is likely to comply with instructions Non pregnant female above 18 years On current treatment with investigational agents for prophylaxis of COVID-19. Plan to travel outside Nigeria from enrolment through 28 days after the last vaccination Participation in other clinical trials Known hypersensitivity to any of the vaccine components History of hypersensitivity or severe allergic reaction Laboratory parameters outside of normal range considered clinically relevant Pregnant woman Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 65 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
Yes 07/01/2022 National health research Ethics committee Nigeria
Ethics Committee Address
Street address City Postal code Country
Federal Ministry of health, Federal Secretariat Abuja Abuja 900211 Nigeria
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Geometric Mean Fold Rise (GMFR) of ≥ 2.5 within the range of 20% non-inferiority to the standard dose of anti-SARS-CoV-2 S antibody response 28 days after immunization detected by ELISA termed as seroconversion. Standard dose- A1-3, B1-3 and C1-3 - Days 28 .
Secondary Outcome 1. Determine 50% Plaque Reduction Neutralization by antibodies against Alpha, Delta, and Kappa variants of SARS-CoV-2. 2. CD4 T cells and CD8 T cells quantitation 3. IFNα, γ-and IL-2 producing CD4 and CD8 T lymphocytes Standard dose- A1-3, B1-3 and C1-3 - Days 28, 84 and 252 . Extended dose interval Arms A 4-6, B4-6 and C4 and C5 - Days 302 and 390.
Primary Outcome Geometric Mean Fold Rise (GMFR) of ≥ 2.5 within the range of 20% non-inferiority to the standard dose of anti-SARS-CoV-2 S antibody response 28 days after immunization detected by ELISA termed as seroconversion. Standard dose- A1-3, B1-3 and C1-3 - Days 28 .
Secondary Outcome 1. Determine 50% Plaque Reduction Neutralization by antibodies against Alpha, Delta, and Kappa variants of SARS-CoV-2. 2. CD4 T cells and CD8 T cells quantitation 3. IFNα, γ-and IL-2 producing CD4 and CD8 T lymphocytes Standard dose- A1-3, B1-3 and C1-3 - Days 28, 84 and 252 . Extended dose interval Arms A 4-6, B4-6 and C4 and C5 - Days 302 and 390.
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Nigerian Institute of Medical Research 6 Edmund crescent Yaba Lagos 10001 Nigeria
National Pharmaceutical Research and Development 205 Idu Industrial Layout Abuja Nigeria
Delta State University Teaching Hospital Delta State University Teaching Hospital Road Oghara Delta state Nigeria
Nnamdi Azikiwe University Teaching Hospital Old Onitsha Road Nnewi Anambra State Nigeria
Aminu Kano University Teaching Hospital 2 zaria Road Kano Nigeria
FUNDING SOURCES
Name of source Street address City Postal code Country
Good Ventures Foundation 314 Lytton Ave Palo Alto, CA United States 94301 Palo Alto CA USA 94301 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Nigeria Federal Ministry of health Federal Secretariat Abuja 900211 Nigeria Public Institution
COLLABORATORS
Name Street address City Postal code Country
National Agency for Food and Drug Administration and Control Plot 2032 Olusegun Obasanjo Way, Wuse Zone 7 Abuja 900281 Nigeria
Nigerian Institute of Pharmaceutical Research and Development 205 Idu Industrial Layout Abuja 900102 Nigeria
National Primary Health Care Development Agency 681/682, Port Harcourt Crescent, Garki Abuja 900247 Nigeria
CONTACT PEOPLE
Role Name Email Phone Street address
Public Enquiries Babatunde Lawal Salalo tundesalako@hotmail.com +2348033832637 6 Edmund crescent
City Postal code Country Position/Affiliation
Yaba Lagos 10001 Nigeria Director General Nigerian Institute of medical Research Lagos
Role Name Email Phone Street address
Principal Investigator Oliver Ezechi oezechi@yahoo.co.uk +2348033065683 6 Edmund crescent
City Postal code Country Position/Affiliation
Yaba Lagos 10001 Nigeria Director of research Nigerian Institute of medical Research Lagos
Role Name Email Phone Street address
Scientific Enquiries Abideen Salako salako.abideennaheem@gmail.com +2348034854995 6 Edmund crescent
City Postal code Country Position/Affiliation
Yaba Lagos 10001 Nigeria Consultant Paediatrician Nigerian Institute of medical Research Lagos
Role Name Email Phone Street address
Public Enquiries Obi Adigwe o.p.adigwe@gmail.com +2348051559005 205 Idu Industrial layout
City Postal code Country Position/Affiliation
Abuja 900102 Nigeria Director General Nigerian Institute of Pharmaceutical Research and Development
Role Name Email Phone Street address
Public Enquiries Mojisola Adeyeye cn.adeyeye@nafdac.gov.ng +2348034099032 Plot 2032 Olusegun Obasanjo Way, Wuse Zone 7
City Postal code Country Position/Affiliation
Wuse Abuja 900281 Nigeria Director General National Agency for Food and Drug Administration and Control
Role Name Email Phone Street address
Public Enquiries Faisal Shauib faisal.shauib@nphcda.gov.ng +2348037039806 681/682, Port Harcourt Crescent, G
City Postal code Country Position/Affiliation
Garki Abuja FCT 900247 Nigeria Executive Secretary National primary Healthcare Development Agency
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes No individual participant data will be shared. Results will be published by the investigators in academic journals. Sharing of generated study data will be carried out in several different ways. We plan to make our results available to researchers and potential collaborators interested in COVID -19 vaccine Analytic Code,Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol 12months after study completion Data access will be controlled by the data management unit of Nigerian Institute of medical research Lagos . All data request should be sent to the head of Data management Unit at hod_dmu@nimr.gov.ng with concept note and data analytic plan and use
URL Results Available Results Summary Result Posting Date First Journal Publication Date
www.nimr.gov.ng 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 Public title 20/05/2022 Decided to do complete blinding Safety & Immunogenicity of Fractional Doses of Vaccines Among Nigerian Adults- A Randomised Non-Inferiority Double Blind Trial Safety & Immunogenicity of Fractional Doses of Vaccines Among Nigerian Adults- A Randomised Non-Inferiority Triple Blind Trial
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Official scientific title 20/05/2022 Moderna vaccine will; be face out of the country programme and replaced with Pfizer vaccine Safety & Immunogenicity of Fractional Doses of Moderna, AstraZeneca, and Janssen Covid-19 Vaccines Among Nigerian Adults- A Randomised Non-Inferiority Double Blind Trial Safety & Immunogenicity of Fractional Doses of Pfizer, AstraZeneca, and Janssen Covid-19 Vaccines Among Nigerian Adults- A Randomised Non-Inferiority Triple Blind Trial
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated trial start date 20/05/2022 Logistics challenges prevent starting as early planned . Also time to complete clinical trial and NAFDAC regulatory registration 01 Feb 2022 30 May 2022
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Actual trial start date 20/05/2022 Not started recruitment 01 Feb 2022
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Actual trial start date 20/05/2022 Not started recruitment 01 Feb 2022
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Actual trial start date 21/11/2024 Vaccine Logistics and trial site preparation and readiness 21 Jun 2022
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated date of last follow up 20/05/2022 To ensure complete recruitment and follow up because of the delayed starting date 31 Jan 2023 29 Apr 2023
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Completion date 20/05/2022 To allow for data cleaning and analysis 31 Jul 2022 28 Oct 2022
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Completion date 21/11/2024 Delay in starting and recruitment challenges and delays 28 Oct 2022 01 Apr 2024
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Target no of participants 20/05/2022 Recalculated sample size to ensure power 1500 1812
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Final no of participants 21/11/2024 some sites recruited a little more. initial state target participants was the minimum sample size 1894
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 21/11/2024 However data management on going Not yet recruiting Completed
Section Name Field Name Date Reason Old Value Updated Value
Study Design Masking / blinding 20/05/2022 Completed blinding Outcome Assessors, Participants Outcome Assessors, Care giver/Provider, Participants
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 20/05/2022 Experimental group appropriately inserted here Experimental Group, Fractional COVID 19 vaccines, AstraZeneca COVID-19 vaccine • Standard dosing interval ( 6 weeks between 1st and 2nd dose) o Group A1: 1.25 x 1010 viral particle o Group A2: 2.5 x 1010 viral particle • Extended dosing interval ( 20 weeks between 1st and 2nd dose) o Group A4: 1.25 x 1010 viral particle o Group A5: 2.5 x 1010 viral particle o Group A6: 5.0 x 1010 viral particle Janssen COVID-19 Vaccine • Standard dosing interval ( 12 weeks between 1st and 2nd dose) o Group B1: 1.25 x 1010 viral particle o Group B2: 2.5 x 1010 viral particle • Extended dosing interval ( 24 weeks between 1st and 2nd dose) o Group B4: 1.25 x 1010 viral particle o Group B5: 2.5 x 1010 viral particle o Group B6: 5.0 x 1010 viral particle Pfizer BioNTech COVID-19 vaccine • Standard dosing interval ( 6 weeks between 1st and 2nd dose) o Group C1: 15ug • Extended dosing interval ( 20 weeks between 1st and 2nd dose) o Group C3: 30ug , Group A • Standard dosing interval ( 6 weeks between 1st and 2nd dose):Group A1-2) • Extended dosing interval ( 20 weeks between 1st and 2nd dose):Group A4-6) Group B • Standard dosing interval ( 12 weeks between 1st and 2nd dose): Group B1-2) • Extended dosing interval ( 24 weeks between 1st and 2nd dose):Group B4-6) Group C • Standard dosing interval ( 6 weeks between 1st and 2nd dose): Group C1-2) • Extended dosing interval ( 20 weeks between 1st and 2nd dose):Group C3) , A multicenter double-blinded, randomized trial of fractional doses of AstraZeneca, Pfizer, and Janseen COVID-19 vaccines at the standard dosage schedules and at extended schedules . Eligible participants will be randomised into three groups with 17 arms (14 arms of experimental groups). The volunteers in Group A (Arms A1, A2, A4, A5, A6) will receive two doses of AstraZeneca COVID – 19 vaccines. While Arms A1 and A2 will receive 1.25 X1010 , and 2.5 X1010 viral particles respectively at the standard dosing interval of 6 weeks between first and second doses, the Arms A4, A5 and A6 will receive 1.25 X1010 , 2.5 X1010 and 5.0 X 1010 viral particles respectively at an extended dosing interval of 20 weeks between first and second doses The volunteers in Group B (Arms B1, B2, B4, B5, B6) will receive two doses of Janssen COVID – 19 vaccines. While Arms B1 and B2 will receive 1.25 X1010 ,and 2.5 X1010 viral particles respectively at the standard dosing interval of 12 weeks between first and second doses, the Arms B4, B5 and B6 will receive 1.25 X1010 , 2.5 X1010 and 5.0 X 1010 viral particles respectively at an extended dosing interval of 24 weeks between first and second doses The volunteers in Group C - Arms C1, C2, and C3 will receive two doses of Pfizer COVID vaccines respectively. Arms C1 and C2 will receive 15ug and 30 ug respectively at the standard dosing interval of 6 weeks between first and second doses. Arms C3 will receive 30ug at the extended dosing interval of 20 weeks between first and second doses. , 1308,
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 20/05/2022 Recalculated sample size and modern dropped for Pfizer vaccine because of phasing out of Moderna in the country Control Group, Fractional COVID 19 vaccines, •Group A3 : Two doses of 5.0 x 1010 viral particle AstraZeneca COVID-19 vaccine 6 weeks apart •Group B3: Two doses of 5.0 x 1010 viral particle Janssen COVID-19 Vaccine 12 weeks apart •Group C3: Single dose 100ug Moderna-mRNA-1273 COVID-19 vaccine , Group A3 - 6 weeks between 1st and 2nd dose Group B3 - 12 weeks between 1st and 2nd dose Group C3 - Single dose , A multicenter double-blinded, randomized trial of fractional doses of AstraZeneca, Moderna-mRNA-1273, and Janseen COVID-19 vaccines at the standard dosage schedules and at extended schedules . Eligible participants will be randomised into three groups with 17 arms (three of which are control arms). The volunteers in Group A3 will receive two doses of AstraZeneca COVID Vaccine (5.0 X 1010 viral particles) at the standard dosing interval of 6 weeks between first and second doses. The volunteers in Group B3 will receive two doses of Janssen COVID – 19 vaccines(5.0 X 1010 viral particles) at the standard dosing interval of 12 weeks between first and second doses. . The volunteers in Group C3 wreceive a single dose of 100ug. , 88, Active-Treatment of Control Group Control Group, Fractional COVID 19 vaccines, •Group A3 : Two doses of 5.0 x 1010 viral particle AstraZeneca COVID-19 vaccine 6 weeks apart •Group B3: Two doses of 5.0 x 1010 viral particle Janssen COVID-19 Vaccine 12 weeks apart •Group C2: Single dose 30ug Pfizer BioNTech COVID-19 vaccine , Group A3 - 6 weeks between 1st and 2nd dose Group B3 - 12 weeks between 1st and 2nd dose Group C2 - 6 weeks between 1st and 2nd dose, A multicenter double-blinded, randomized trial of fractional doses of AstraZeneca, Pfizer, and Janseen COVID-19 vaccines at the standard dosage schedules and at extended schedules . Eligible participants will be randomised into three groups with 17 arms (three of which are control arms). The volunteers in Group A3 will receive two doses of AstraZeneca COVID Vaccine (5.0 X 1010 viral particles) at the standard dosing interval of 6 weeks between first and second doses. The volunteers in Group B3 will receive two doses of Janssen COVID – 19 vaccines(5.0 X 1010 viral particles) at the standard dosing interval of 12 weeks between first and second doses. . The volunteers in Group C2 will receive the standard dosing (30ug) interval of 6 weeks between first and second doses. , 901, Active-Treatment of Control Group
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 20/05/2022 Experimental arm appropriately entered . Moderna vaccine phased out of the country and replaced by Pfizer Experimental Group, Fractional COVID 19 vaccines, AstraZeneca COVID-19 vaccine • Standard dosing interval ( 6 weeks between 1st and 2nd dose) o Group A1: 1.25 x 1010 viral particle o Group A2: 2.5 x 1010 viral particle • Extended dosing interval ( 20 weeks between 1st and 2nd dose) o Group A4: 1.25 x 1010 viral particle o Group A5: 2.5 x 1010 viral particle o Group A6: 5.0 x 1010 viral particle Janssen COVID-19 Vaccine • Standard dosing interval ( 12 weeks between 1st and 2nd dose) o Group B1: 1.25 x 1010 viral particle o Group B2: 2.5 x 1010 viral particle • Extended dosing interval ( 24 weeks between 1st and 2nd dose) o Group B4: 1.25 x 1010 viral particle o Group B5: 2.5 x 1010 viral particle o Group B6: 5.0 x 1010 viral particle Pfizer BioNTech COVID-19 vaccine • Standard dosing interval ( 6 weeks between 1st and 2nd dose) o Group C1: 15ug • Extended dosing interval ( 20 weeks between 1st and 2nd dose) o Group C3: 30ug , Group A • Standard dosing interval ( 6 weeks between 1st and 2nd dose):Group A1-2) • Extended dosing interval ( 20 weeks between 1st and 2nd dose):Group A4-6) Group B • Standard dosing interval ( 12 weeks between 1st and 2nd dose): Group B1-2) • Extended dosing interval ( 24 weeks between 1st and 2nd dose):Group B4-6) Group C • Standard dosing interval ( 6 weeks between 1st and 2nd dose): Group C1-2) • Extended dosing interval ( 20 weeks between 1st and 2nd dose):Group C3) , A multicenter double-blinded, randomized trial of fractional doses of AstraZeneca, Pfizer, and Janseen COVID-19 vaccines at the standard dosage schedules and at extended schedules . Eligible participants will be randomised into three groups with 17 arms (14 arms of experimental groups). The volunteers in Group A (Arms A1, A2, A4, A5, A6) will receive two doses of AstraZeneca COVID – 19 vaccines. While Arms A1 and A2 will receive 1.25 X1010 , and 2.5 X1010 viral particles respectively at the standard dosing interval of 6 weeks between first and second doses, the Arms A4, A5 and A6 will receive 1.25 X1010 , 2.5 X1010 and 5.0 X 1010 viral particles respectively at an extended dosing interval of 20 weeks between first and second doses The volunteers in Group B (Arms B1, B2, B4, B5, B6) will receive two doses of Janssen COVID – 19 vaccines. While Arms B1 and B2 will receive 1.25 X1010 ,and 2.5 X1010 viral particles respectively at the standard dosing interval of 12 weeks between first and second doses, the Arms B4, B5 and B6 will receive 1.25 X1010 , 2.5 X1010 and 5.0 X 1010 viral particles respectively at an extended dosing interval of 24 weeks between first and second doses The volunteers in Group C - Arms C1, C2, and C3 will receive two doses of Pfizer COVID vaccines respectively. Arms C1 and C2 will receive 15ug and 30 ug respectively at the standard dosing interval of 6 weeks between first and second doses. Arms C3 will receive 30ug at the extended dosing interval of 20 weeks between first and second doses. , 1308,
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 20/05/2022 As in the intervention Experimental Group, Fractional COVID 19 vaccines, AstraZeneca COVID-19 vaccine • Standard dosing interval ( 6 weeks between 1st and 2nd dose) o Group A1: 1.25 x 1010 viral particle o Group A2: 2.5 x 1010 viral particle • Extended dosing interval ( 20 weeks between 1st and 2nd dose) o Group A4: 1.25 x 1010 viral particle o Group A5: 2.5 x 1010 viral particle o Group A6: 5.0 x 1010 viral particle Janssen COVID-19 Vaccine • Standard dosing interval ( 12 weeks between 1st and 2nd dose) o Group B1: 1.25 x 1010 viral particle o Group B2: 2.5 x 1010 viral particle • Extended dosing interval ( 24 weeks between 1st and 2nd dose) o Group B4: 1.25 x 1010 viral particle o Group B5: 2.5 x 1010 viral particle o Group B6: 5.0 x 1010 viral particle Moderna-mRNA-1273 COVID-19 vaccine • Standard dosing interval ( 4 weeks between 1st and 2nd dose) o Group C1: 25ug o Group C2: 50ug • Extended dosing interval ( 20 weeks between 1st and 2nd dose) o Group C4: 25ug o Group C5: 50ug, Group A • Standard dosing interval ( 6 weeks between 1st and 2nd dose):Group A1-2) • Extended dosing interval ( 20 weeks between 1st and 2nd dose):Group A4-6) Group B • Standard dosing interval ( 12 weeks between 1st and 2nd dose): Group B1-2) • Extended dosing interval ( 24 weeks between 1st and 2nd dose):Group B4-6) Group C • Standard dosing interval ( 4 weeks between 1st and 2nd dose): Group C1-2) • Extended dosing interval ( 20 weeks between 1st and 2nd dose):Group C4-5), A multicenter double-blinded, randomized trial of fractional doses of AstraZeneca, Moderna-mRNA-1273, and Janseen COVID-19 vaccines at the standard dosage schedules and at extended schedules . Eligible participants will be randomised into three groups with 17 arms (14 arms of experimental groups). The volunteers in Group A (Arms A1, A2, A4, A5, A6) will receive two doses of AstraZeneca COVID – 19 vaccines. While Arms A1 and A2 will receive 1.25 X1010 , and 2.5 X1010 viral particles respectively at the standard dosing interval of 6 weeks between first and second doses, the Arms A4, A5 and A6 will receive 1.25 X1010 , 2.5 X1010 and 5.0 X 1010 viral particles respectively at an extended dosing interval of 20 weeks between first and second doses The volunteers in Group B (Arms B1, B2, B4, B5, B6) will receive two doses of Janssen COVID – 19 vaccines. While Arms B1 and B2 will receive 1.25 X1010 ,and 2.5 X1010 viral particles respectively at the standard dosing interval of 12 weeks between first and second doses, the Arms B4, B5 and B6 will receive 1.25 X1010 , 2.5 X1010 and 5.0 X 1010 viral particles respectively at an extended dosing interval of 24 weeks between first and second doses The volunteers in Group C - Arms C1, C2, C4,and C5 will receive two doses of Moderna COVID vaccines respectively. Arms C1 and C2 will receive 25ug and 50 ug respectively at the standard dosing interval of 4 weeks between first and second doses. Arms C4 and C5 will receive 25ug and 50 ug respectively at the extended dosing interval of 20 weeks between first and second doses. , 88, Experimental Group, Fractional COVID 19 vaccines, AstraZeneca COVID-19 vaccine • Standard dosing interval ( 6 weeks between 1st and 2nd dose) o Group A1: 1.25 x 1010 viral particle o Group A2: 2.5 x 1010 viral particle • Extended dosing interval ( 20 weeks between 1st and 2nd dose) o Group A4: 1.25 x 1010 viral particle o Group A5: 2.5 x 1010 viral particle o Group A6: 5.0 x 1010 viral particle Janssen COVID-19 Vaccine • Standard dosing interval ( 12 weeks between 1st and 2nd dose) o Group B1: 1.25 x 1010 viral particle o Group B2: 2.5 x 1010 viral particle • Extended dosing interval ( 24 weeks between 1st and 2nd dose) o Group B4: 1.25 x 1010 viral particle o Group B5: 2.5 x 1010 viral particle o Group B6: 5.0 x 1010 viral particle Pfizer BioNTech COVID-19 vaccine • Standard dosing interval ( 6 weeks between 1st and 2nd dose) o Group C1: 15ug • Extended dosing interval ( 20 weeks between 1st and 2nd dose) o Group C3: 30ug , Group A • Standard dosing interval ( 6 weeks between 1st and 2nd dose):Group A1-2) • Extended dosing interval ( 20 weeks between 1st and 2nd dose):Group A4-6) Group B • Standard dosing interval ( 12 weeks between 1st and 2nd dose): Group B1-2) • Extended dosing interval ( 24 weeks between 1st and 2nd dose):Group B4-6) Group C • Standard dosing interval ( 6 weeks between 1st and 2nd dose): Group C1-2) • Extended dosing interval ( 20 weeks between 1st and 2nd dose):Group C3), A multicenter double-blinded, randomized trial of fractional doses of AstraZeneca, Pfizer, and Janseen COVID-19 vaccines at the standard dosage schedules and at extended schedules . Eligible participants will be randomised into three groups with 17 arms (14 arms of experimental groups). The volunteers in Group A (Arms A1, A2, A4, A5, A6) will receive two doses of AstraZeneca COVID – 19 vaccines. While Arms A1 and A2 will receive 1.25 X1010 , and 2.5 X1010 viral particles respectively at the standard dosing interval of 6 weeks between first and second doses, the Arms A4, A5 and A6 will receive 1.25 X1010 , 2.5 X1010 and 5.0 X 1010 viral particles respectively at an extended dosing interval of 20 weeks between first and second doses The volunteers in Group B (Arms B1, B2, B4, B5, B6) will receive two doses of Janssen COVID – 19 vaccines. While Arms B1 and B2 will receive 1.25 X1010 ,and 2.5 X1010 viral particles respectively at the standard dosing interval of 12 weeks between first and second doses, the Arms B4, B5 and B6 will receive 1.25 X1010 , 2.5 X1010 and 5.0 X 1010 viral particles respectively at an extended dosing interval of 24 weeks between first and second doses The volunteers in Group C - Arms C1, C2, and C3 will receive two doses of Pfizer COVID vaccines respectively. Arms C1 and C2 will receive 15ug and 30 ug respectively at the standard dosing interval of 6 weeks between first and second doses. Arms C3 will receive 30ug at the extended dosing interval of 20 weeks between first and second doses. , 901,
Section Name Field Name Date Reason Old Value Updated Value
Intervention Intervention List 20/05/2022 This arm is the control and not experimental In addition Moderna phased out of the country and replaced by Pfizer Control Group, Standard COVID 19 vaccines, Group A3 : Two doses of 5.0 x 1010 viral particle AstraZeneca COVID-19 vaccine 6 weeks apart •Group B3: Two doses of 5.0 x 1010 viral particle Janssen COVID-19 Vaccine 12 weeks apart •Group C2: Single dose 30ug Pfizer BioNTech COVID-19 vaccine , Group A3 - 6 weeks between 1st and 2nd dose Group B3 - 12 weeks between 1st and 2nd dose Group C2 - 6 weeks between 1st and 2nd dose , A multicenter double-blinded, randomized trial of fractional doses of AstraZeneca, Pfizer, and Janseen COVID-19 vaccines at the standard dosage schedules and at extended schedules . Eligible participants will be randomised into three groups with 17 arms (three of which are control arms). The volunteers in Group A3 will receive two doses of AstraZeneca COVID Vaccine (5.0 X 1010 viral particles) at the standard dosing interval of 6 weeks between first and second doses. The volunteers in Group B3 will receive two doses of Janssen COVID – 19 vaccines(5.0 X 1010 viral particles) at the standard dosing interval of 12 weeks between first and second doses. . The volunteers in Group C2 will receive the standard dosing (30ug) interval of 6 weeks between first and second doses. , 504, Active-Treatment of Control Group
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 21/11/2024 To simplified statistical analysis, and usability of result for policy based on advice of country's ministry programme staff Primary Outcome, Geometric Mean Fold Rise (GMFR) of ≥ 2.5 within the range of 20% non-inferiority to the standard dose of anti-SARS-CoV-2 S antibody response 14days after immunization detected by ELISA termed as seroconversion., Standard dose- A1-3, B1-3 and C1-3 - Days 14, 28, 42, 56, and 85. Extended dose interval Arms A 4-6, B4-6 and C4 and C5 - Days 28, 57, 150, 210, 302 and 390. Primary Outcome, Geometric Mean Fold Rise (GMFR) of ≥ 2.5 within the range of 20% non-inferiority to the standard dose of anti-SARS-CoV-2 S antibody response 28 days after immunization detected by ELISA termed as seroconversion., Standard dose- A1-3, B1-3 and C1-3 - Days 28 .
Section Name Field Name Date Reason Old Value Updated Value
Outcome OutCome List 21/11/2024 as in the primary outcome Secondary Outcome, 1. Determine 50% Plaque Reduction Neutralization by antibodies against Alpha, Delta, and Kappa variants of SARS-CoV-2. 2. CD4 T cells and CD8 T cells quantitation 3. IFNα, γ-and IL-2 producing CD4 and CD8 T lymphocytes , Standard dose- A1-3, B1-3 and C1-3 - Days 14, 28, 42, 56, and 85. Extended dose interval Arms A 4-6, B4-6 and C4 and C5 - Days 28, 57, 150, 210, 302 and 390. Secondary Outcome, 1. Determine 50% Plaque Reduction Neutralization by antibodies against Alpha, Delta, and Kappa variants of SARS-CoV-2. 2. CD4 T cells and CD8 T cells quantitation 3. IFNα, γ-and IL-2 producing CD4 and CD8 T lymphocytes , Standard dose- A1-3, B1-3 and C1-3 - Days 28, 84 and 252 . Extended dose interval Arms A 4-6, B4-6 and C4 and C5 - Days 302 and 390.