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

Anticipated date of last follow up

29/04/2023

Actual Last follow-up date

28/10/2022

Anticipated target sample size (number of participants)

1812

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	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 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.
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.

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	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	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
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	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	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
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	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
Trial Information	Actual trial start date	20/05/2022	Not started recruitment	01 Feb 2022

Pan African Clinical Trials Registry