Study of Recombinant Protein Vaccines With Adjuvant as a Primary Series and as a Booster Dose Against COVID-19 in Adults 18 Years of Age and Older

COVID-19 Clinical Trial

Official title:

Immunogenicity and Safety of SARS-CoV-2 Recombinant Protein Vaccines With AS03 Adjuvant in Adults 18 Years of Age and Older as a Primary Series and Immunogenicity and Safety of a Booster Dose of SARS-CoV-2 Adjuvanted Recombinant Protein Vaccines (Two Monovalent and One Bivalent)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04762680
• Other study ID #: VAT00002
• Secondary ID: U1111-1251-46162
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: February 24, 2021
• Est. completion date: June 29, 2023

Study information

• Verified date: May 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objectives of the study are:

To assess the safety profile of the study vaccines in each study intervention group.

To assess the neutralizing antibody profile after primary series vaccination in SARS-CoV-2-naïve adults.

To demonstrate that a booster dose of monovalent or bivalent SARS-CoV-2 vaccine given to adults previously vaccinated with an authorized/approved COVID-19 vaccine induces an immune response that is non-inferior to the response induced by a twodose priming series with the monovalent vaccine, and superior to that observed immediately before booster.

The secondary objectives of the study are:

To assess the neutralizing and binding antibody profiles after primary series vaccination at pre-defined time points during the study.

To assess the neutralizing and binding antibody responses of booster vaccination.

To describe the occurrences of laboratory-confirmed symptomatic COVID19 after primary series and booster vaccination.

To describe the occurrences of serologically-confirmed SARS-CoV-2 infection after primary series vaccination.

Description:

The duration of each participant's participation in the study will be approximately:

Original Phase 2 part: 365 days postinjection 2 (ie, 386 days total). Supplemental Cohorts 1 and 2: 365 days post-booster injection (ie, 366 days total).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3385
• Est. completion date: June 29, 2023
• Est. primary completion date: June 29, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

-Aged 18 years or older on the day of inclusion. - -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 mut 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 vaccination until at least 12 weeks after the last vaccination (ie, second dose of primary series or booster injection). A participant of childbearing potential must have a negative highly sensitive pregnancy test (urine or serum as required by local regulation) within 4 hours before any dose of study intervention. - -Informed consent form has been signed and dated.

Able to attend all scheduled visits and to comply with all study procedures. SARS-CoV-2 rapid serodiagnostic test performed at the time of enrollment to detect presence of SARS-CoV-2 antibodies (Original Phase 2 Cohort).

For persons living with human immunodeficiency virus (HIV), stable HIV infection determined by participant currently on antiretrovirals with CD4 count > 200/mm3.

Does not intend to receive an authorized/approved COVID-19 vaccine from first vaccination to 3 weeks after the second vaccination despite encouragement by the investigator to receive the authorized vaccine available to them at the time of enrollment.

Supplemental cohorts: for participants originally enrolled in the Phase II cohort of the study, informed consent has to be signed and dated for transitioning to Supplemental Cohort 2.

Supplemental cohorts, Booster arms: received a complete primary vaccination series with an authorized/conditionally approved mRNA COVID-19 vaccine (mRNA-1273 [Moderna] or BNT162b2 [Pfizer/BioNTech]) or adenovirus-vectored COVID-19 vaccine (ChAdOx1 nCoV-19 [Oxford University/AstraZeneca] or Ad26.CoV2.S [J&J/Janssen]), with the last dose administered a minimum of 4 months prior to inclusion but not longer than 10 months prior to inclusion.

Exclusion Criteria:

-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 trial procedures based on Investigator or designee'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.

Receipt of solid-organ or bone marrow transplants in the past 180 days. Receipt of anti-cancer chemotherapy in the last 90 days. Receipt of immunoglobulins, blood, or blood-derived products in the past 3 months.

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 trial 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.

Applicable to Original Phase II Cohort, Supplemental Cohort 1 and Cohort 2 Comparator Group: Prior administration of a coronavirus vaccine (SARS-CoV-2, SARS-CoV, Middle East Respiratory Syndrome [MERS-CoV]). Participation at the time of study enrollment (or in the 30 days preceding the first study vaccination) or planned participation during the present study trial period in another clinical study investigating a vaccine, drug, medical device, or medical procedure. Exclusion criterion for the Supplemental Cohort 1 and Cohort 2 comparator group: positive rapid diagnostic test for SARS-CoV-2 antibodies at time of enrollment.

Exclusion criterion for participants in Supplemental Cohort 2 who were primed as participant in the Original Phase II Cohort of the present study: Receipt of authorized/conditionally approved COVID-19 vaccine after enrollment in Original Phase 2 Cohort.

Exclusion criterion for all Booster groups: Documented virologically-confirmed SARS-CoV-2 infection (by NAAT) after first dose of primary immunization.

Related Conditions & MeSH terms

• COVID-19

Intervention

Biological:
• SARS-CoV-2 recombinant protein vaccine Phase 2 Formulation 1
Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection
• SARS-CoV-2 recombinant protein vaccine Phase 2 Formulation 2
Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection
• SARS-CoV-2 recombinant protein vaccine Phase 2 Formulation 3
Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection
• SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (D614)-AS03, Dosage A
Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection
• SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03
Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection
• SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (D614)-AS03, Dosage B
Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection
• SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03 Alternative Exploratory Formulation 1
Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection
• SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03 Alternative Exploratory Formulation 2
Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection
• SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03 Alternative Exploratory Formulation 3
Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection
• SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03 Alternative Exploratory Formulation 4
Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection
• SARS-CoV-2 adjuvanted recombinant protein vaccine, bivalent (D614+B.1.351)-AS03
Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection

Locations

Country	Name	City	State
Australia	Investigational Site Number : 0360003	Norwood
Australia	Investigational Site Number : 0360001	South Brisbane	Queensland
Australia	Investigational Site Number : 0360002	Southport
Australia	Investigational Site Number : 0360005	Westmead
Australia	Investigational Site Number : 0360004	Woodville
France	Investigational Site Number : 2500013	Dijon
France	Investigational Site Number : 2500008	Limoges
France	Investigational Site Number : 2500014	Lyon
France	Investigational Site Number : 2500015	Marseille
France	Investigational Site Number : 2500016	Marseille
France	Investigational Site Number : 2500006	Nantes
France	Investigational Site Number : 2500005	Paris
France	Investigational Site Number : 2500003	Pessac
France	Investigational Site Number : 2500007	Pierre Benite
France	Investigational Site Number : 2500004	Rennes
France	Investigational Site Number : 2500002	Tours Cedex 1
Honduras	Investigational Site Number : 3400002	Municipio Del Distrito Central
Honduras	Investigational Site Number : 3400001	San Pedro Sula
New Zealand	Investigational Site Number : 5540002	Christchurch
New Zealand	Investigational Site Number : 5540007	Nawton
New Zealand	Investigational Site Number : 5540010	Nelson
New Zealand	Investigational Site Number : 5540005	New Lynn	Auckland
New Zealand	Investigational Site Number : 5540001	Rotorua
Spain	Investigational Site Number : 7240009	Madrid
Spain	Investigational Site Number : 7240016	Majadahonda	Madrid
Spain	Investigational Site Number : 7240013	Santiago De Compostela	Galicia [Galicia]
Spain	Investigational Site Number : 7240008	Valencia
Spain	Investigational Site Number : 7240003	Vigo
United Kingdom	Investigational Site Number : 8260017	Bath	Somerset
United Kingdom	Investigational Site Number : 8260014	Doncaster
United Kingdom	Investigational Site Number : 8260016	Gloucester
United Kingdom	Investigational Site Number : 8260010	Harrow
United Kingdom	Investigational Site Number : 8260015	London
United Kingdom	Investigational Site Number : 8260011	Runcorn	Halton
United Kingdom	Investigational Site Number : 8260012	Southampton
United Kingdom	Investigational Site Number : 8260013	Surrey	Sutton
United States	AES Austin Site Number : 8400191	Austin	Texas
United States	Synexus - Clinical Research Advantage, Inc. Site Number : 8400270	Birmingham	Alabama
United States	Brigham and Women's Hospital Site Number : 8400199	Boston	Massachusetts
United States	NYU VC-Augustana Site Number : 8400267	Brooklyn	New York
United States	Synexus Chandler Site Number : 8400251	Chandler	Arizona
United States	Chicago Clinical Research Institute, Inc. Site Number : 8400269	Chicago	Illinois
United States	Emory University Decatur Site Number : 8400201	Decatur	Georgia
United States	Synexus Clinical Research Evansville Site Number : 8400272	Evansville	Indiana
United States	Synexus - Glendale. Site Number : 8400271	Glendale	Arizona
United States	Research Centers of America Site Number : 8400089	Hollywood	Florida
United States	Baptist Health Center for Clinical Research Site Number : 8400077	Little Rock	Arkansas
United States	Charles R. Drew University of Medicine and Science Site Number : 8400220	Los Angeles	California
United States	Optimal Research, LLC Site Number : 8400057	Melbourne	Florida
United States	Yale University Site Number : 8400239	New Haven	Connecticut
United States	Research Works INC Site Number : 8400045	New Orleans	Louisiana
United States	Columbia University Irving Medical Center Site Number : 8400203	New York	New York
United States	New York University Langone Vaccine Center Site Number : 8400230	New York	New York
United States	Coastal Carolina Research Center Site Number : 8400097	North Charleston	South Carolina
United States	Velocity Clinical Research, Omaha Site Number : 8400030	Omaha	Nebraska
United States	Synexus Clinical Research US, Inc. - Orlando Site Number : 8400179	Orlando	Florida
United States	Optimal Research Site Number : 8400187	Peoria	Illinois
United States	University of Pittsburgh Site Number : 8400233	Pittsburgh	Pennsylvania
United States	American Indian Clinical Trials Research Network Site Number : 8400204	Rapid City	South Dakota
United States	University of Rochester Site Number : 8400207	Rochester	New York
United States	Optimal Research, LLC Rockville Site Number : 8400048	Rockville	Maryland
United States	Peninsula Research Associates, Inc. Site Number : 8400094	Rolling Hills Estates	California
United States	Synexus St. Louis Site Number : 8400100	Saint Louis	Missouri
United States	Optimal Research Site Number : 8400173	San Diego	California
United States	Holy Name Medical Center Site Number : 8400072	Teaneck	New Jersey
United States	The George Washington University Site Number : 8400212	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi Pasteur, a Sanofi Company	GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Australia,  France,  Honduras,  New Zealand,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Presence of immediate adverse events	Immediate adverse events include unsolicited adverse events occurring within 30 minutes after injection.	Within 30 minutes after vaccination
Primary	Presence of solicited injection site or systemic reactions	Injection site reactions: injection site pain, erythema and swelling. Systemic reactions: fever, headache, malaise and myalgia.	Within 7 days after vaccination
Primary	Presence of unsolicited adverse events	Adverse events other than solicited reactions.	Within 21 days after vaccination
Primary	Presence of serious adverse events	Serious adverse events are reported throughout the study.	From Day 1 to Day 387
Primary	Presence of adverse events of special interest	Adverse events of special interest are reported throughout the study.	From Day 1 to Day 387
Primary	Presence of medically-attended adverse events	Medically-attended adverse events are new onset or a worsening of a condition that prompts the participant or participant's parent/guardian to seek unplanned medical advice at a physician's office or Emergency Department.	From Day 1 to Day 387
Primary	Neutralizing antibody titer at Day 1	Neutralizing antibody titers are expressed as geometric mean titers.	Day 1
Primary	Neutralizing antibody titer at Day 36	Neutralizing antibody titers are expressed as geometric mean titers.	Day 36
Primary	Neutralizing antibody titer fold-rise post-vaccination	Neutralizing antibody titer fold-rise post-vaccination.	From Day 1 to Day 36
Primary	2-fold rise and 4-fold-rise in neutralization antibody titer	Fold-rise in antibody neutralization titer post-vaccination relative to Day 1.	From Day 1 to Day 36
Primary	Responders, as determined by neutralizing antibody titers at Day 36	Responders, defined as participants who had baseline values below lower limit of quantification (LLOQ) with detectable neutralization titer above assay LLOQ at each pre-defined time point and participants with baseline values above LLOQ with a 4-fold increase in neutralizing antibody titer at Day 36	From Day 1 to Day 36
Primary	Neutralizing antibody titer at Day 1 (pre-booster injection)	Neutralizing antibody titers are expressed as geometric mean titers.	Day 1 (pre-booster injection)
Primary	Neutralizing antibody titer at Day 15 (post-booster injection)	Neutralizing antibody titers are expressed as geometric mean titers.	Day 15 (post-booster injection)
Primary	Neutralizing antibody titer at Day 36 (Cohorts 1 and 2 Comparator Group)	Neutralizing antibody titers are expressed as geometric mean titers.	Day 36
Primary	Responders, as determined by neutralizing antibody titers at Day 36 (Cohorts 1 and 2 Comparator Group)	Responders are defined as participants with a 4-fold-or greater rise in serum neutralization titer [pre/post] at Day 36 relative to Day 1	From Day 1 to Day 36
Secondary	Neutralizing antibody titer at all pre-defined time points		Day 1, Day 22, Day 36, Day 78, Day 134, Day 202, Day 292 and Day 387
Secondary	Neutralizing antibody titer fold-rise post-vaccination at all pre-defined time points	Fold-rise in antibody neutralization titer post-vaccination relative to Day 1.	Day 1, Day 22, Day 36, Day 78, Day 134, Day 202, Day 292 and Day 387
Secondary	Responders, as determined by neutralizing antibody titers at each pre-defined time point	Responders, defined as participants who had baseline values below LLOQ with detectable neutralization titer above assay LLOQ at each pre-defined time point and participants with baseline values above LLOQ with a 4-fold increase in neutralizing antibody titer at each pre-defined timepoint.	Day 1, Day 22, Day 36, Day 78, Day 134, Day 202, Day 292 and Day 387
Secondary	2-fold rise and 4-fold-rise in neutralization antibody titer at all pre-defined time points	Fold-rise in antibody neutralization titer post-vaccination relative to Day 1.	Day 1, Day 22, Day 36, Day 78, Day 134, Day 202, Day 292 and Day 387
Secondary	Binding antibody fold-rise	Fold-rise in concentration relative to Day 1.	Day 1, Day 22, Day 36, Day 78, Day 134, Day 202, Day 292 and Day 387
Secondary	Binding antibody concentrations		Day 1, Day 22, Day 36, Day 78, Day 134, Day 202, Day 292 and Day 387
Secondary	2-fold-rise and 4-fold rise in binding antibody concentration	Fold-rise in concentration relative to Day 1.	Day 1, Day 22, Day 36, Day 78, Day 134, Day 202, Day 292 and Day 387
Secondary	Responders, as determined by binding antibody concentrations	Responders are defined as participants who had baseline values below LLOQ with detectable anti concentration above assay LLOQ at each pre-defined time point and participants with baseline values above LLOQ with a 4-fold increase in anti-S antibody concentration at each pre-defined time point.	Day 1, Day 22, Day 36, Day 78, Day 134, Day 202, Day 292 and Day 387
Secondary	Occurrences of laboratory-confirmed symptomatic COVID-19	Symptomatic COVID-19 is defined as laboratory-confirmed SARS-CoV-2 infection accompanied by protocol-defined COVID-19-like illness. Laboratory-confirmed SARS-CoV-2 infection is defined as a positive result for SARS CoV-2 by nucleic acid amplification test (NAAT), done by the central laboratory or locally, on at least one respiratory sample.	From Day 1 to Day 387
Secondary	Occurrences of symptomatic COVID-19 episodes associated with hospitalization	Symptomatic COVID-19 is defined as laboratory-confirmed SARS-CoV-2 infection accompanied by protocol-defined COVID-19-like illness.	From Day 1 to Day 387
Secondary	Occurrences of severe symptomatic COVID-19	Symptomatic COVID-19 is defined as laboratory-confirmed SARS-CoV-2 infection accompanied by protocol-defined COVID-19-like illness with pre-defined criteria of severity.	From Day 1 to Day 387
Secondary	Occurrences of death associated with symptomatic COVID-19	Symptomatic COVID-19 is defined as laboratory-confirmed SARS-CoV-2 infection accompanied by protocol-defined COVID-19-like illness.	From Day 1 to Day 387
Secondary	Occurrences of serologically-confirmed SARS-CoV-2 infection	Serologically-confirmed SARS-CoV-2 infection is defined as a positive result in a serum sample for antibodies against SARS-CoV-2.	From Day 1 to Day 387
Secondary	Neutralizing antibody titer at all pre-defined time points post-booster and booster comparator injection		Day 1 and Day 15 (post-booster injection) and Day 36
Secondary	Neutralizing antibody titer fold-rise post-vaccination at all pre-defined time points post-booster and booster comparator injection	Neutralizing antibody titer fold-rise post-vaccination.	Day 1 and Day 15 (post-booster injection) and Day 36
Secondary	2-fold rise and 4-fold-rise in neutralization antibody titer at all pre-defined time points post-booster and booster comparator injection	Neutralizing antibody titer fold-rise post-vaccination.	Day 1 and Day 15 -post-booster injection) and Day 36
Secondary	Seroresponse rate post-booster and booster comparator injection	Seroresponse rate is defined as the percentage or participants with 4-fold-or greater rise in serum neutralization titer [pre/post] at post-vaccination relative to pre-vaccination.	Day 1 and Day 15 (post-booster injection) and Day 36
Secondary	Binding antibody concentrations post-booster injection		Day 1, Day 15, Day 29, Day 91, Day 181, and Day 366 (post-booster injection)
Secondary	Binding antibody fold-rise post-booster injection	Fold-rise in concentration relative to Day 1.	Day 1, Day 15, Day 29, Day 91, Day 181, and Day 366 (post-booster injection)
Secondary	2-fold-rise and 4-fold rise in binding antibody concentration post-booster injection	Fold-rise in concentration relative to Day 1.	Day 1, Day 15, Day 29, Day 91, Day 181, and Day 366 (post-booster injection)