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Study of Monovalent and Bivalent Recombinant Protein Vaccines Against COVID-19 in Adults 18 Years of Age and Older (VAT00008)

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ClinicalTrials.gov Identifier: NCT04904549
Recruitment Status : Recruiting
First Posted : May 27, 2021
Last Update Posted : October 8, 2021
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )

Tracking Information
First Submitted Date  ICMJE May 26, 2021
First Posted Date  ICMJE May 27, 2021
Last Update Posted Date October 8, 2021
Actual Study Start Date  ICMJE May 26, 2021
Estimated Primary Completion Date January 27, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 26, 2021)
  • Occurrences of symptomatic COVID-19 [ Time Frame: From ≥ 14 days after the second injection to Day 387 ]
    Symptomatic COVID-19 is defined as virologically-confirmed SARS-CoV-2 infection accompanied by protocol-defined COVID-19-like illness.
  • Presence of solicited injection site or systemic reactions [ Time Frame: Within 7 days after vaccination ]
    Injection site reactions: injection site pain, erythema and swelling. Systemic reactions: fever, headache, malaise, myalgia, arthralgia and chills.
  • Presence of non-serious unsolicited adverse events [ Time Frame: Within 21 days after vaccination ]
    Adverse events other than solicited reactions.
  • Presence of immediate adverse events [ Time Frame: Within 30 minutes after vaccination ]
    Immediate adverse events include unsolicited injection site and systemic adverse events occurring within 30 minutes after injection.
  • Presence of medically attended adverse events [ Time Frame: From Day 1 to Day 387 ]
    Medically attended adverse events will be assessed throughout the study.
  • Presence of serious adverse events [ Time Frame: From Day 1 to Day 387 ]
    Serious adverse events will be assessed throughout the study.
  • Presence of adverse events of special interest [ Time Frame: From Day 1 to Day 387 ]
    Adverse events of special interest will be assessed throughout the study.
  • Presence of virologically-confirmed SARS-CoV-2 infections and/or symptomatic COVID-19 [ Time Frame: From Day 1 to Day 387 ]
    Percentage of participants with positive result for SARS-CoV-2 infection by Nucleic Acid Amplification Test (NAAT) on at least one respiratory sample accompanied or not by protocol-defined clinical COVID-19 symptoms.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 26, 2021)
  • Occurrences of SARS-CoV-2 infection [ Time Frame: From ≥ 14 days after the second injection to Day 387 ]
    SARS-CoV-2 infection is defined as a serologically-confirmed SARS-CoV-2 infection or virologically-confirmed SARS-CoV-2 infection.
  • Occurrence of severe COVID-19 [ Time Frame: From ≥ 14 days after the second injection to Day 387 ]
  • Occurrences of asymptomatic SARS-CoV-2 infection [ Time Frame: From Day 1 to Day 387 ]
    Asymptomatic SARS-CoV-2 infection is defined as SARS-CoV-2 infection, with no reported COVID-19-like illness episodes between enrollment and 14 days after the timepoint at which SARS-CoV-2 infection is ascertained.
  • Viral copies/mL in respiratory samples [ Time Frame: From Day 1 to Day 387 ]
  • Number of days with positive NAAT [ Time Frame: From Day 1 to Day 387 ]
  • Occurrences of positive NAAT in respiratory samples at each follow-up timepoint during symptomatic COVID-19 [ Time Frame: From Day 1 to Day 387 ]
  • Occurrences of Centers for Disease Control and Prevention (CDC)-defined COVID-19 [ Time Frame: From Day 1 to Day 387 ]
    Virologically-confirmed SARS-CoV-2 infection with at least one of CDC-defined clinical symptoms.
  • Occurrences of hospitalized COVID-19 [ Time Frame: From Day 1 to Day 387 ]
    Hospitalized COVID-19 is defined as an episode of symptomatic COVID-19 that requires inpatient hospitalization.
  • Occurrences of symptomatic COVID-19 with severity of moderate COVID-19 or worse. [ Time Frame: From Day 1 to Day 387 ]
    Composite endpoint of at least one of moderate or severe COVID-19.
  • Neutralizing antibody titer [ Time Frame: Day 1, Day 22, Day 43, Day 78, Day 134, Day 202, Day 292, and Day 387 ]
  • Responders, as determined by neutralizing antibody titers [ Time Frame: Day 1, Day 22, Day 43, Day 78, Day 134, Day 202, Day 292, and Day 387 ]
    Responders are defined as participants who had baseline values below lower limit of quantification (LLOQ) with quantifiable neutralization titer above assay LLOQ at each pre-defined post-vaccination time point and participants with baseline values above LLOQ with a 4-fold increase in neutralizing antibody
  • Neutralizing antibody titer fold-rise post-vaccination at all pre-defined time points [ Time Frame: Day 1, Day 22, Day 43, Day 78, Day 134, Day 202, Day 292, and Day 387 ]
    Fold-rise in antibody neutralization titer post-vaccination relative to Day 1.
  • 2-fold rise and 4-fold-rise in neutralization antibody titer at all pre-defined time points [ Time Frame: Day 1, Day 22, Day 43, Day 78, Day 134, Day 202, Day 292, and Day 387 ]
    Fold-rise in antibody neutralization titer post-vaccination relative to Day 1.
  • Severity of symptoms associated with symptomatic COVID-19 episode [ Time Frame: From Day 1 to Day 387 ]
  • Occurrences of COVID-19 in each severity rating [ Time Frame: From Day 1 to Day 387 ]
    COVID-19 severity score based on the ordinal scale of clinical assessment (7-point ordinal scale)
  • Death associated with COVID-19 [ Time Frame: From Day 1 to day 387 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Monovalent and Bivalent Recombinant Protein Vaccines Against COVID-19 in Adults 18 Years of Age and Older
Official Title  ICMJE A Parallel-group, Phase III, Multi-stage, Modified Double-blind, Multi-armed Study to Assess the Efficacy, Safety, and Immunogenicity of Two SARS-CoV-2 Adjuvanted Recombinant Protein Vaccines (Monovalent and Bivalent) for Prevention Against COVID-19 in Adults 18 Years of Age and Older
Brief Summary

The primary objectives of the study are:

  • To assess, in participants who are severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) naïve, the clinical efficacy of the SARS-CoV-2 vaccines for the prevention of symptomatic COVID-19 occurring ≥ 14 days after the second injection.
  • To assess the safety of the SARS-CoV-2 vaccines compared to placebo throughout the study.

The main secondary objectives of the study are to assess, in SARS-CoV-2 naïve participants, the efficacy of the SARS-CoV-2 vaccines against:

  • SARS-CoV-2 infection occurring ≥ 14 days after the second injection.
  • Severe disease occurring ≥ 14 days after the second injection.
  • Asymptomatic infection and symptomatic COVID-19 occurring ≥ 14 days after the first injection.
Detailed Description The duration of participation in the study will be approximately 365 days post-last injection (ie, approximately 386 days total) for each participant.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
The study is designed to demonstrate clinical efficacy of each of the two SARS-CoV-2 adjuvanted recombinant protein vaccines (monovalent and bivalent). In Stage 1, the monovalent vaccine will be evaluated against a placebo control. In Stage 2, bivalent vaccine will be assessed against a placebo control.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Participants, outcome assessors, Investigators, laboratory personnel, and sponsor trial staff are blinded to intervention group; and those preparing the study interventions are unblinded to vaccine assignment group.
Primary Purpose: Prevention
Condition  ICMJE COVID-19 (Healthy Volunteers)
Intervention  ICMJE
  • Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine (monovalent)
    Pharmaceutical form: emulsion for injection. Route of administration: intramuscular injection
  • Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine (bivalent)
    Pharmaceutical form: emulsion for injection. Route of administration: intramuscular injection.
  • Biological: Placebo
    Pharmaceutical form: liquid. Route of administration: intramuscular administration.
Study Arms  ICMJE
  • Experimental: Stage 1: SARS-CoV-2 vaccine
    2 injections of monovalent SARS-CoV-2 vaccine at Day 1 and Day 22
    Intervention: Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine (monovalent)
  • Placebo Comparator: Stage 1: Placebo
    2 injections of placebo at Day 1 and Day 22
    Intervention: Biological: Placebo
  • Experimental: Stage 2: SARS-CoV-2 vaccine
    2 injections of bivalent SARS-CoV-2 vaccine at Day 1 and Day 22
    Intervention: Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine (bivalent)
  • Placebo Comparator: Stage 2: Placebo
    2 injections of placebo at Day 1 and Day 22
    Intervention: Biological: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 1, 2021)
21046
Original Estimated Enrollment  ICMJE
 (submitted: May 26, 2021)
37430
Estimated Study Completion Date  ICMJE January 27, 2023
Estimated Primary Completion Date January 27, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Aged 18 years or older on the day of inclusion.
  • For persons living with human immunodeficiency virus (HIV), stable HIV infection determined by participant currently on antiretrovirals with CD4 count > 200/mm3.
  • SARS-CoV-2 rapid serodiagnostic test performed at the time of enrollment to detect presence of SARS-CoV-2 antibodies.
  • Does not intend to receive an authorized/approved COVID-19 vaccine despite encouragement by the Investigator to receive the authorized vaccine available to them at the time of enrollment.
  • A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies:
  • Is of non-childbearing potential. To be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year or surgically sterile, or
  • Is of childbearing potential and agrees to use an effective contraceptive method or abstinence from at least 4 weeks prior to the first study intervention administration until at least 12 weeks after the second study intervention administration.

A participant of childbearing potential must have a negative highly sensitive pregnancy test (urine or serum as required by local regulation).

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

  • Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to a vaccine containing any of the same substances.
  • Dementia or any other cognitive condition at a stage that could interfere with following the study procedures based on Investigator's judgment.
  • Self-reported thrombocytopenia, contraindicating intramuscular (IM) vaccination based on Investigator's judgment
  • Bleeding disorder, or receipt of anticoagulants in the past 21 days preceding inclusion, contraindicating IM vaccination based on Investigator's judgment.
  • Unstable acute or chronic illness that in the opinion of the Investigator or designee poses additional risk as a result of participation or that could interfere with the study procedures.
  • Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided.
  • Receipt of any vaccine in the 30 days preceding or on the day of the first study vaccination or planned receipt of any vaccine between the first study vaccination and in the 30 days following the second study vaccination except for influenza vaccination, which may be received at any time in relation to study intervention.
  • Prior administration of a coronavirus vaccine (SARS-CoV-2, SARS-CoV, Middle East Respiratory Syndrome).
  • Receipt of solid-organ or bone marrow transplants in the past 180 days.
  • Receipt of anti-cancer chemotherapy in the last 90 days.
  • Participation at the time of study enrollment (or in the 30 days preceding the first study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext option 6 Contact-US@sanofi.com
Listed Location Countries  ICMJE Colombia,   Ghana,   Honduras,   India,   Japan,   Kenya,   Nepal,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04904549
Other Study ID Numbers  ICMJE VAT00008
U1111-1264-3238 ( Registry Identifier: ICTRP )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/
Responsible Party Sanofi ( Sanofi Pasteur, a Sanofi Company )
Study Sponsor  ICMJE Sanofi Pasteur, a Sanofi Company
Collaborators  ICMJE GlaxoSmithKline
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP