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Efficacy of Different COVID-19 Vaccine Combinations in Inducing Long-term Humoral Immunity [PRIBIVAC] (PRIBIVAC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05142319
Recruitment Status : Recruiting
First Posted : December 2, 2021
Last Update Posted : December 2, 2021
Sponsor:
Collaborators:
A*Star
Duke-NUS Graduate Medical School
KK Women's and Children's Hospital
Information provided by (Responsible Party):
Barnaby Young, Tan Tock Seng Hospital

Brief Summary:

This study will assess heterologous prime-boost-boost vaccine regimens in comparison with an homologous regimen in order to compare short and long-term immunogenicity of different COVID-19 vaccine combinations against the ancestral SARS-CoV-2 as well as different variants of concern (VOCs).

Hypothesis: One or more heterologous prime-boost-boost COVID-19 vaccine combinations will produce humoral and cellular immunity that is non-inferior to an homologous prime-boost-boost vaccination against wildtype SARS-CoV-2 and/or 1≥ VOC.


Condition or disease Intervention/treatment Phase
COVID-19 Biological: Homologous mRNA booster vaccine Biological: Heterologous mRNA booster vaccine Biological: Non-mRNA booster vaccine A Biological: Non-mRNA booster vaccine B Biological: Non-mRNA booster vaccine C Phase 3

Detailed Description:

ICOVID-19 vaccination programs worldwide have so far focused on raising population immunity through the primary COVID-19 vaccine series. In Singapore two mRNA vaccines developed by Pfizer/BioNTech (BNT162b2) and Moderna (mRNA-1273), have been granted interim authorisation by Health Science Authority (HSA) under the pandemic special access route (PSAR). Some other COVID-19 vaccines are authorised by HSA for use in Singapore as part of the Special Access Route (SAR) through their addition to the WHO Emergency Use List (EUL). Many of these vaccines have been widely used in other countries, including an inactivated whole virus vaccine developed by Sinovac; an adenovirus-based formulation developed by Oxford-AstraZenaca; and a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector vaccine developed by Johnson & Johnson / Janssen.

Vaccination in Singapore started first for frontline and healthcare workers with BNT162b2 at the end of December 2020. Over the following months this vaccine program was extended first to older adults and then the general population, while mRNA-1273 was also introduced alongside BNT162b2. By August 2021 >75% of Singapore's resident population was fully vaccinated. The pivotal phase 3 clinical trials of BNT162b2 and mRNA-1273 reported a vaccine efficacy of >95% against symptomatic and severe disease. However, data from individuals vaccinated with mRNA-1273 showed gradually declining neutralising antibody titres by 6 months post inoculation. In addition, the emergence of variants of concern (VOCs) capable of evading protective immunity (from a wildtype SARS-CoV-2 virus vaccine) has raised the need for a long term COVID-19 immunisation strategy. Several fundamental questions need to be addressed in order to design this: Will a 3rd booster dose offer clinical benefit? Who needs a booster vaccination? How long after the primary series should it be administered? And, which vaccine should be used?

This study will assess the immunogenicity and safety of heterologous boost COVID-19 vaccine regimens (intervention groups 1-4) compared with a homologous boost regimen (control arm). Potential participants would have already received a homologous prime-boost vaccination with BNT162b2 or mRNA-1273 prior to randomisation. The booster vaccine for the control arm will be the homologous mRNA vaccine (e.g. BNT162b2 + BNT162b2 + BNT162b2 or mRNA-1273 + mRNA-1273 + mRNA-1273), while for individuals randomised to intervention group 1 the mRNA booster vaccine administered will be heterologous to the primary series (e.g. BNT162b2 + BNT162b2 + mRNA-1273 or mRNA-1273 + mRNA-1273 + BNT162b2).

The booster vaccine candidates for intervention arms 2-4 will be an alternative COVID-19 vaccine. This may include vaccines that have received full or interim authorisation from HSA, are available under the Special Access Route (SAR) for vaccines that are part of the WHO Emergency Use List (EUL), or are currently under clinical development.

Control group: Homologous mRNA booster vaccine Intervention group 1: Heterologous mRNA booster vaccine Intervention group 2: Non-mRNA booster vaccine A Intervention group 3: Non-mRNA booster vaccine B Intervention group 4: Non-mRNA booster vaccine C

Vaccine candidates A, B and C may enter the study at different time points, participants will be randomised at equal probability to the available intervention arms at the time of randomisation. This will reduce the risk of bias (e.g. participant preference for a certain arm) compared with a non-randomised design. An ideal scenario is to have all the selected vaccines approved prior to the start of recruitment. However, due to the unknown time of availability of vaccine candidates A, B and C, and the urgency of the current situation, recruitment to the control and intervention group 1 will start first.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 600 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Masking Description: Only study participants will be blinded to the vaccine allocation. This is to reduce the risk of bias in participant-reported AEs. The study participant will be unblinded at Day-28 visit (Visit 3).
Primary Purpose: Prevention
Official Title: Heterologous Prime-boost-boost Vaccine Combinations for Long-term Humoral and Cellular Immunity Against COVID-19
Actual Study Start Date : October 12, 2021
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : April 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Homologous mRNA booster vaccine
BNT162b2 + BNT162b2 + BNT162b2 or mRNA-1273 + mRNA-1273 + mRNA-1273
Biological: Homologous mRNA booster vaccine
Single intradermal injection. The vaccine dose will be according to manufacturer's instructions.

Experimental: Heterologous mRNA booster vaccine
BNT162b2 + BNT162b2 + mRNA-1273 or mRNA-1273 + mRNA-1273 + BNT162b2
Biological: Heterologous mRNA booster vaccine
Single intradermal injection. The vaccine dose will be according to manufacturer's instructions.

Experimental: Non-mRNA booster vaccine A
BNT162b2 + BNT162b2 + vaccine A or mRNA-1273 + mRNA-1273 + vaccine A
Biological: Non-mRNA booster vaccine A
Single intradermal injection. The vaccine dose will be according to manufacturer's instructions.

Experimental: Non-mRNA booster vaccine B
BNT162b2 + BNT162b2 + vaccine B or mRNA-1273 + mRNA-1273 + vaccine B
Biological: Non-mRNA booster vaccine B
Single intradermal injection. The vaccine dose will be according to manufacturer's instructions.

Experimental: Non-mRNA booster vaccine C
BNT162b2 + BNT162b2 + vaccine C or mRNA-1273 + mRNA-1273 + vaccine C
Biological: Non-mRNA booster vaccine C
Single intradermal injection. The vaccine dose will be according to manufacturer's instructions.




Primary Outcome Measures :
  1. SARS-CoV-2 anti-spike immunoglobulins [ Time Frame: Day 28 ]
    To determine the presence and levels of anti-SARS-COV-2 in human sera


Secondary Outcome Measures :
  1. SARS-CoV-2 anti-spike immunoglobulins [ Time Frame: Day 1, 7, 180, 360 ]
    To determine the presence and levels of anti-SARS-COV-2 in human sera

  2. Level of SARS-CoV-2 neutralising antibodies [ Time Frame: Day 1, 7, 28, 180, 360 ]
    To examine the neutralising capacity of the antibodies in the human sera

  3. Quantitative T-cell responses to spike proteins [ Time Frame: Day 1, 7, 28, 180, 360 ]
    Quantitative T-cell responses to the vaccines will be measured using SARS-CoV-2 peptides from spike protein to stimulate the PBMCs isolated from donor's blood.

  4. Solicited local and systemic reaction [ Time Frame: Up to 7 days post-vaccination ]
    The participant will be given a diary to record all the local and general symptoms experienced after receiving the vaccination.

  5. Changes from baseline in laboratory safety measures [ Time Frame: Baseline and 7 days post-vaccination ]

    Blood will be taken from the participant during screening visit prior to vaccination (also known as baseline) for the following clinical labs: a) Full blood count inclusive of differential blood count and platelet count; b) Liver panel including albumin, total bilirubin, ALP and ALT; c) Renal panel including sodium, potassium and creatinine; d) Cardiology panel including creatine kinase and troponin.

    The results of the above clinical tests will be compared with repeat tests at Day 7 post-vaccination.


  6. Unsolicited adverse events (AEs) [ Time Frame: 28 days post-vaccination ]
  7. Serious adverse events (SAEs) and AEs of special interest (eg. myocarditis, pericarditis), medically attended AEs [ Time Frame: Up to 360 days post-vaccination ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Willing and able to provide informed consent for participation in this study;
  2. Aged ≥21years at the time of study enrolment;
  3. Received the second dose of BNT162b2 or mRNA-1273 Coronavirus Disease 2019 vaccines at least 6 months prior to enrolment;
  4. Willing and able to comply with all scheduled visits, vaccination plan, laboratory tests and other study procedures.

Exclusion Criteria:

  1. Known history of SARS-CoV-2 or SARS-CoV-1 infection;
  2. Previously received an investigational coronavirus vaccine;
  3. Previously received a SARS-CoV-2 monoclonal antibody;
  4. Current or planned simultaneous participation in another interventional study;
  5. A history of anaphylaxis, urticaria, or other significant adverse reaction requiring medical intervention after receipt of a COVID-19 vaccine, or otherwise have a contraindication to one of the available study vaccines per the approved label;
  6. Individuals who are immunocompromised (e.g. active leukaemia or lymphoma, generalised malignancy, aplastic anaemia, solid organ transplant, bone marrow transplant, current radiation therapy congenital immunodeficiency, HIV/AIDS with CD4 lymphocyte count < 200 and patients on immunosuppressant medications);
  7. Received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to Screening (for corticosteroids >/= 20 milligram per day of prednisone equivalent). Topical tacrolimus is allowed if not used within 14 days prior to Day 1;
  8. Individuals who are pregnant or breast feeding;
  9. Chronic illness that, in the opinion of the study team, is at a stage where it might interfere with trial conduct or completion;
  10. Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalised involuntarily;
  11. Current alcohol abuse or drug addiction that might interfere with the ability to comply with trial procedures in the opinion of the study team;
  12. Moderate or severe acute illness/infection (according to study team's judgement) on the day of vaccination, or febrile illness (temperature ≥ 37.5°C). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05142319


Contacts
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Contact: Barnaby Young, Dr 63577458 Barnaby_Young@ncid.sg

Locations
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Singapore
National Centre for Infectious Diseases (NCID) Recruiting
Singapore, Singapore, 308442
Contact: Barnaby Young, Dr    63577458    barnaby_young@ncid.sg   
Principal Investigator: Barnaby Young, Dr         
Sub-Investigator: David Lye, A/Prof         
Sub-Investigator: Sapna Sadarangani, Dr         
Sub-Investigator: Ray Lin, Dr         
Sub-Investigator: Tau Hong Lee, Dr         
Sub-Investigator: Po Ying Chia, Dr         
Sub-Investigator: Suma Rao, Dr         
Sub-Investigator: Sean Ong, Dr         
Sponsors and Collaborators
Tan Tock Seng Hospital
A*Star
Duke-NUS Graduate Medical School
KK Women's and Children's Hospital
Investigators
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Principal Investigator: Barnaby Young, Dr National Centre for Infectious Diseases
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Barnaby Young, Senior Consultant, Tan Tock Seng Hospital
ClinicalTrials.gov Identifier: NCT05142319    
Other Study ID Numbers: 2021/00821
First Posted: December 2, 2021    Key Record Dates
Last Update Posted: December 2, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: All study findings and documents will be regarded as confidential. The investigators and other study personnel must not disclose such information without prior written approval from the PI. Participant confidentiality will be strictly maintained to the extent possible under the law and local hospital policy. Identifiable information will be removed from any published data.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Barnaby Young, Tan Tock Seng Hospital:
Vaccine booster
SARS-CoV-2
Coronavirus
Antibody
Humoral immunity
Cellular immunity
Immunogenicity
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs