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

NCT05142319 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: 2021/00821
• Study Type: interventional
• Target: 326
• Locations: 1 country
• Sites: 1

Brief Summary

PRIBIVAC will assess a heterologous prime-boost-boost strategy in comparison with a 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). Initial phases of the study (Phases A-C) have studied homologous versus heterologous vaccines at the first booster, later phases (Phase D) will study these as the second booster. 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. In Phases A-C of the study the primary 2 dose mRNA vaccine series was defined as 'Prime-boost'. For phase D we will define these 2 doses as 'Prime' and the 3rd vaccine dose as 'Boost'.

Conditions

COVID-19

Keywords

Vaccine booster; SARS-CoV-2; Coronavirus; Antibody; Humoral immunity; Cellular immunity; Immunogenicity

Outcome Measures

Primary Outcomes (1)

• SARS-CoV-2 anti-spike immunoglobulins

  To determine the presence and levels of anti-SARS-COV-2 in human sera

  Day 28

Secondary Outcomes (7)

• SARS-CoV-2 anti-spike immunoglobulins

  Day 1, 7, 180, 360

• Level of SARS-CoV-2 neutralising antibodies

  Day 1, 7, 28, 180, 360

• Quantitative T-cell responses to spike proteins

  Day 1, 7, 28, 180, 360

• Solicited local and systemic reaction

  Up to 7 days post-vaccination

• Changes from baseline in laboratory safety measures (Phases A-C only)

  Baseline and 7 days post-vaccination

Other Outcomes (2)

• Vaccine efficacy

  Throughout the study

• Residual mRNA vaccine

  Day 7

Study Arms (4)

Homologous mRNA booster vaccine

ACTIVE COMPARATOR

BNT162b2 + BNT162b2 + BNT162b2 or mRNA-1273 + mRNA-1273 + mRNA-1273

Biological: Homologous mRNA booster vaccine

Heterologous mRNA booster vaccine

EXPERIMENTAL

BNT162b2 + BNT162b2 + mRNA-1273 or mRNA-1273 + mRNA-1273 + BNT162b2

Biological: Heterologous mRNA booster vaccine

COVAXIN

EXPERIMENTAL

BNT162b2 + BNT162b2 + COVAXIN or mRNA-1273 + mRNA-1273 + COVAXIN

Biological: COVAXIN

Nuvaxovid

EXPERIMENTAL

BNT162b2 + BNT162b2 + Nuvaxovid or mRNA-1273 + mRNA-1273 + Nuvaxovid

Biological: Nuvaxovid

Interventions

Homologous mRNA booster vaccine BIOLOGICAL

Single intradermal injection. The vaccine dose will be according to manufacturer's instructions.

Homologous mRNA booster vaccine

Heterologous mRNA booster vaccine BIOLOGICAL

Single intradermal injection. The vaccine dose will be according to manufacturer's instructions.

Heterologous mRNA booster vaccine

COVAXIN BIOLOGICAL

Single intradermal injection at 6ug (0.5ml) per dose.

COVAXIN

Nuvaxovid BIOLOGICAL

Single intradermal injection at 5mcg (0.5mL) per dose.

Nuvaxovid

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Known history of SARS-CoV-2 or SARS-CoV-1 infection;
• Previously received an investigational coronavirus vaccine;
• Previously received a SARS-CoV-2 monoclonal antibody;
• Current or planned simultaneous participation in another interventional study;
• 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;
• 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);
• 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;
• Individuals who are pregnant or breast feeding;
• Chronic illness that, in the opinion of the study team, is at a stage where it might interfere with trial conduct or completion;
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalised involuntarily;
• Current alcohol abuse or drug addiction that might interfere with the ability to comply with trial procedures in the opinion of the study team;
• 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.

Sponsors & Collaborators

• Tan Tock Seng Hospital: lead
• A*Star: collaborator
• KK Women's and Children's Hospital: collaborator
• Duke-NUS Graduate Medical School: collaborator

Study Sites (1)

National Centre for Infectious Diseases (NCID)

Singapore, Singapore, 308442, Singapore

Location

Related Publications (6)

• Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, Perez JL, Perez Marc G, Moreira ED, Zerbini C, Bailey R, Swanson KA, Roychoudhury S, Koury K, Li P, Kalina WV, Cooper D, Frenck RW Jr, Hammitt LL, Tureci O, Nell H, Schaefer A, Unal S, Tresnan DB, Mather S, Dormitzer PR, Sahin U, Jansen KU, Gruber WC; C4591001 Clinical Trial Group. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020 Dec 31;383(27):2603-2615. doi: 10.1056/NEJMoa2034577. Epub 2020 Dec 10.

  PMID: 33301246 BACKGROUND

• Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, Diemert D, Spector SA, Rouphael N, Creech CB, McGettigan J, Khetan S, Segall N, Solis J, Brosz A, Fierro C, Schwartz H, Neuzil K, Corey L, Gilbert P, Janes H, Follmann D, Marovich M, Mascola J, Polakowski L, Ledgerwood J, Graham BS, Bennett H, Pajon R, Knightly C, Leav B, Deng W, Zhou H, Han S, Ivarsson M, Miller J, Zaks T; COVE Study Group. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2021 Feb 4;384(5):403-416. doi: 10.1056/NEJMoa2035389. Epub 2020 Dec 30.

  PMID: 33378609 BACKGROUND

• Poh XY, Torres-Ruesta A, Yoong T, Wong N, Tan CW, Rouers A, Chavatte JM, Goh YS, Rao S, Chia PY, Ong SWX, Lee TH, Sadarangani SP, Lin RJH, Neo V, Kam IKJ, Huang Y, Hor PX, Loh CY; PRIBIVAC study group; Yeoh AY, Lim DRX, Chia W, Ren EC, Lin RTP, Fong SW, Renia L, Lye DC, Wang LF, Ng LFP, Young BE. Immunogenicity of mRNA vs. BBV152 vaccine boosters against Omicron subvariants: Final results from Phase B of the PRIBIVAC study, a randomized clinical trial. Vaccine. 2024 Nov 14;42(25):126275. doi: 10.1016/j.vaccine.2024.126275. Epub 2024 Sep 5.

  PMID: 39241318 DERIVED

• Goh YS, Fong SW, Hor PX, Loh CY, Wang B, Salleh SNM, Ngoh EZX, Lee RTC, Poh XY, Rao S, Chia PY, Ong SWX, Lee TH, Lim C, Teo J, Pada S, Sun LJ, Ong DLS, Somani J, Lee ES, Maurer-Stroh S, Wang CI, Leo YS, Lye DC, Young BE, Ng LFP, Renia L; NCID Study Group; COVID-19 Cohort Study Group. Variant-Specific IgA Protects Against Omicron Infection. J Infect Dis. 2024 Aug 16;230(2):e287-e291. doi: 10.1093/infdis/jiad525.

  PMID: 37996071 DERIVED

• Poh XY, Lee IR, Lim C, Teo J, Rao S, Chia PY, Ong SWX, Lee TH, Lin RJH, Ng LFP, Ren EC, Lin RTP, Wang LF, Renia L, Lye DC, Young BE. Evaluation of the safety and immunogenicity of different COVID-19 vaccine combinations in healthy individuals: study protocol for a randomized, subject-blinded, controlled phase 3 trial [PRIBIVAC]. Trials. 2022 Jun 16;23(1):498. doi: 10.1186/s13063-022-06345-2.

  PMID: 35710572 DERIVED

• Poh XY, Tan CW, Lee IR, Chavatte JM, Fong SW, Prince T, Hartley C, Yeoh AYY, Rao S, Chia PY, Ong SWX, Lee TH, Sadarangani SP, Lin RJH, Lim C, Teo J, Lim DRX, Chia W, Hiscox JA, Ng LFP, Ren EC, Lin RTP, Renia L, Lye DC, Wang LF, Young BE. Antibody Response of Heterologous vs Homologous Messenger RNA Vaccine Boosters Against the Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant: Interim Results from the PRIBIVAC Study, a Randomized Clinical Trial. Clin Infect Dis. 2022 Dec 19;75(12):2088-2096. doi: 10.1093/cid/ciac345.

  PMID: 35543372 DERIVED

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Interventions

BBV152 COVID-19 vaccine; NVX-CoV2373 adjuvated lipid nanoparticle

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Barnaby Young, A/Prof

  National Centre for Infectious Diseases

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: 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).
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Consultant

Study Record Dates

• First Submitted: November 30, 2021
• First Posted: December 2, 2021
• Study Start: October 12, 2021
• Primary Completion: June 1, 2023
• Study Completion: May 7, 2024
• Last Updated: October 15, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)