This study aims to address evidence gaps regarding the safety, reactogenicity and immuneresponses of a heterologous boost of a single dose of Ad26.COV2.S (half or full dose) atpre-specified time intervals in recipients who are documented to have received either1-dose or 2-doses (primary series completion) of inactivated COVID-19 vaccines, Sinovacand/or Sinopharm.
This is a prospective, multi-center, observer-blind Phase 1/2 adaptive study to assess
the safety, reactogenicity, and immunogenicity of a booster dose of Ad26.COV2.S in adults
≥ 18 years of age in Study Part A and Part B. A total of 690 participants will be
recruited. If the optional Group (A4) is feasible and enrolled, the total recruitment
will be 800 participants. Priority enrolment is given to Groups A1 and A2, followed by
Groups A3 and B1. Enrolment of groups are open-label allocation and assessor-masked.
The Study is divided into 2 Parts: Part A and B.
Study Part A is a prospective, multi-center, assessor-masked Phase 1/2 study to assess a
booster dose (3rd dose) of Ad26.COV2.S as an IM injection in the deltoid muscle in adults
who have completed the two-dose homologous primary series of inactivated vaccine of
Sinovac or Sinopharm, 21 to 35 days apart and who meet eligibility criteria. Participants
will receive either the full-dose (5x10^10 vp) or half-dose (2.5x10^10 vp) of the study
product, and at early (45-75 days) or later (90-240 days) time interval and followed from
Visit 1 (V1) to Visit 7 (V7) at 336 days.
A total of 580 adult volunteers aged 18 years or older, who have verified vaccination
cards with documented completion of homologous primary vaccination series with either two
doses of Adsorbed COVID-19 (inactivated) Sinovac (SV) or Sinopharm (SP) vaccine, against
original and novel variants of SARS-CoV-2 will be enrolled. A 20% dropout rate is
assumed. Enrolment is increased to 360 (300+20% dropout) for the safety assessment, to
detect common adverse events with an event rate of 1%.
Part B is a prospective, multi-center, open-label, assessor-masked Phase 1/2 heterologous
prime-boost study to assess the Ad26.COV2.S (full dose) as the 2nd vaccination in
subjects who are documented to all have received the 1st dose of Sinovac or all received
the 1st dose of Sinopharm COVID-19 vaccine, with an interval of 28 days or more, followed
from Visit 1 (V1) to Visit 7 (V7) at 336 days.
Together with the Sponsor, the PIs will decide on the feasibility of enrolment of
participants who all have already received 1 dose of Sinopharm or who all have received
1dose of Sinovac, based on current public health policy and vaccine coverage.
For safety assessment:
Adverse events (AEs) will be systematically collected at all clinic visits. Solicited AEs
will be assessed in all subjects immediately (30 minutes) after each injection. Subjects
(or with necessary supports) will record solicited AEs daily in the Diary Card for the
seven days following injection. If a solicited AE is ongoing at a 7-day post-injection
follow-up visit (Visit 2), or occurs after 7 days post-injection, the event will be
recorded as AE and continued to be followed as per AE monitoring requirements.
Adverse events and special reporting situations, whether serious or non-serious, that are
related to study procedures or that are related to non-investigational sponsor products
will be reported from the time a signed and dated informed consent form (ICF) is obtained
until the end of the study/early withdrawal. All other unsolicited AEs will be reported
from the time of vaccination until completion of the participant's last study-related
procedure. All AESIs, SAEs, and AEs leading to discontinuation from the study (regardless
of the causal relationship) are to be reported from the moment of vaccination until
completion of the participant's last study related procedure.
For immunological assessment:
Primary objectives
1. To assess the IgG immune response against the Spike protein of SARS-CoV-2, measured
by ELISA and compared with baseline (pre-boost titer) at Days 28, 84, 168 and 336
following either half dose (2.5x10^10 virus particles (vp)) or full dose (5x10^10
vp) of Ad26.COV2.S vaccination at pre-specified time intervals in adults who have
already received either one-dose or two-doses of an inactivated COVID-19 vaccine.
2. To assess a subset for functional (neutralizing) humoral immune responses elicited
by each of the regimens as measured by pseudovirus neutralization assay, IgG at
baseline, Days 28, 84, 168 and 336 following Ad26.COV2.S vaccination.
Secondary objective
1. To assess a subset for functional (neutralizing) humoral immune responses elicited
by each of the regimens as measured by microneutralization neutralization assay, IgG
at baseline, Days 28, 84, 168 and 336 following Ad26.COV2.S vaccination.
Exploratory Objectives
1. To characterize PCR-confirmed COVID-19 breakthrough infections following booster
vaccination by assessing anti-S and anti-N IgG.
2. To characterize cellular immune responses including Th1/Th2.
3. To consider statistical tests of noninferiority in comparing the different study
arms.
4. To assess Adenovirus 26 neutralizing antibodies at baseline if feasible.
Study duration: Subjects will be followed for approximately 336 days following
Ad26.COV2.S vaccination. The total study period will be 18 months, including 12-month
follow-up period.
The Clinical Data Management System, including eCRFs, statistical analysis and data
archival are under the responsibility of the center of excellence for Biomedical and
Public Health Informatics (BIOPHICS), the center of data management for clinical research
at the Faculty of Tropical Medicine, Mahidol University.
Based on the final protocol of the study, a comprehensive set of CRFs/eCRFs will be
prepared to capture all the relevant data required for analysis and reporting.
Information about COVID-19 disease, correlates of immunity, safety, and local
epidemiology and public health context regarding the new SARS-CoV-2 virus are rapidly
evolving during the pandemic. Therefore, it is critical to recognize that the approach
outlined in this document may be adapted as new data, expert consensus and public health
policies evolve.
Biological: Full dose of Ad26.COV2. 5x10^10vp
A booster dose (3rd dose) of Ad26.COV2.S as an IM injection in the deltoid muscle in
adults.
Biological: Half dose of Ad26.COV2. 2.5x10^10vp
A booster dose (3rd dose) of Ad26.COV2.S as an IM injection in the deltoid muscle in
adults.
Biological: Full dose of Ad26.COV2. 5x10^10vp
A booster dose (2nd dose) of Ad26.COV2.S as an IM injection in the deltoid muscle in
adults.
Inclusion Criteria:
Potential participants must meet all inclusion criteria to be enrolled and participate in
the study, as follows:
1. Adult male or female aged 18 years or more on the day of signing the ICF, confirmed
by identification cards.
2. Verified, documentation of past COVID-19 vaccination i. Study Part A: having
completed the 2-dose homologous primary regimen (21 to 35 days apart) of inactivated
COVID-19 vaccine of either Sinovac-Sinovac OR Sinopharm-Sinopharm ii. Study Part B:
having received one dose of inactivated COVID-19 vaccine of either Sinovac or
Sinopharm with the appropriate interval period
3. Women of childbearing potential who are test negative with a highly sensitive urine
pregnancy test at Visit 1, prior to study vaccine administration.
4. Subject has provided written informed consent prior to performance of any
study-specific procedures and is willing and has means to be contacted and to
contact the investigator during the study.
5. In the investigator's clinical judgment, the participant is in good health, or has
stable and well-controlled medical conditions.
6. Participant agrees to not donate bone marrow, blood, and blood products from the
study vaccine administration until 3 months after receiving the study vaccine.
Exclusion Criteria:
Potential participants who meet any of the following exclusion criteria will be excluded
from enrolment and participation in the study:
1. The participant has a clinically significant acute illness (this does not include
minor illnesses such as diarrhea or mild upper respiratory tract infection), or is a
patient under investigation (PUI) or has a body temperature ≥38.0ºC (100.4°F) within
24 hours prior to the planned study vaccination. Assignment may be made at a later
date is permitted at the discretion of the investigator. Please notify the Sponsor
(or medical monitor) of this decision.
2. Contraindication to Ad26.COV2.S according to labelling of the product. For example,
if the participant has a known or suspected allergy or history of anaphylaxis or
other serious adverse reactions to vaccines or their excipients (including
specifically the excipients of the study vaccine;refer to the IB (IB Edition 5
Ad26.COV2.S 2021 and its addenda).
3. Pregnant or planning to become pregnant within 3 months after study vaccine
administration
4. Participant has a history or current condition as follows
1. Known documented history of COVID-19 infection prior to enrollment
2. Any confirmed or suspected immunosuppressive or immunodeficient state.
3. Heparin-induced thrombocytopenia or thrombosis in combination with
thrombocytopenia.
4. Acute polyneuropathy (e.g. Guillain-Barré syndrome).
5. Capillary leak syndrome
6. Contraindication to IM injections and blood draws e.g., bleeding disorders.
7. An underlying clinically significant acute or chronic medical condition or
physical examination findings for which, in the opinion of the investigator,
participation would not be in the best interest of the participant (e.g.,
compromise the well being) or that could prevent, limit, or confound the
protocol-specified assessments.
8. Major psychiatric illness which in the investigator's opinion would compromise
the participant's safety or compliance with the study procedures.
5. If the participant received or plans to receive:
1. Licensed live attenuated vaccines - within 28 days before or after planned
administration of study vaccine.
2. Other licensed (not live) vaccines - within 14 days before or after planned
administration of study vaccine.
3. Treatment with immunoglobulins (Ig) in the 3 months or exogenous blood products
(autologous blood transfusions are not exclusionary) in the 4 months before the
planned administration of the study vaccine or has any plans to receive such
treatment during the study.
6. If the participant cannot communicate reliably with the investigator, or, in the
opinion of the investigator, is unlikely to adhere to the requirements of the study
or is unlikely to complete the full course of vaccination and observation.
7. Employee of the study center directly involved with the proposed study or with study
investigators.
Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi,
Bangkok, Thailand
Investigator: Punnee Pitisuttithum, MD
Contact: +66818294906
punnee.pit@mahidol.ac.th
Investigator: Punnee Pitisuttithum, MD
Sant Muangnoicharoen, MD
+66851998989
sant.mua@mahidol.ac.th
Punnee Pitisuttithum, MD, Study Chair
Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University