Clinical trial NCT04762680: 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
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: COVID-19
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2021-02-21
Enrollment: 3385
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: To address the emergence of variant strains, Sanofi Pasteur is developing monovalent and bivalent vaccines for use as universal late booster vaccines which will be studied in additional Phase 3 study cohorts that are added to the initial Phase 2 protocol cohorts. Supplemental Cohorts 1 and 2 will evaluate booster vaccine candidates.
Primary purpose: PREVENTION

Brief 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.

Detailed 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Presence of immediate adverse events
timeFrame: Within 30 minutes after vaccination
measure: Presence of solicited injection site or systemic reactions
timeFrame: Within 7 days after vaccination
measure: Presence of unsolicited adverse events
timeFrame: Within 21 days after vaccination
measure: Presence of serious adverse events
timeFrame: From Day 1 to Day 387
measure: Presence of adverse events of special interest
timeFrame: From Day 1 to Day 387
measure: Presence of medically-attended adverse events
timeFrame: From Day 1 to Day 387
measure: Neutralizing antibody titer at Day 1
timeFrame: Day 1
measure: Neutralizing antibody titer at Day 36
timeFrame: Day 36
measure: Neutralizing antibody titer fold-rise post-vaccination
timeFrame: From Day 1 to Day 36
measure: 2-fold rise and 4-fold-rise in neutralization antibody titer
timeFrame: From Day 1 to Day 36
measure: Responders, as determined by neutralizing antibody titers at Day 36
timeFrame: From Day 1 to Day 36
measure: Neutralizing antibody titer at Day 1 (pre-booster injection)
timeFrame: Day 1 (pre-booster injection)
measure: Neutralizing antibody titer at Day 15 (post-booster injection)
timeFrame: Day 15 (post-booster injection)
measure: Neutralizing antibody titer at Day 36 (Cohorts 1 and 2 Comparator Group)
timeFrame: Day 36
measure: Responders, as determined by neutralizing antibody titers at Day 36 (Cohorts 1 and 2 Comparator Group)
timeFrame: From Day 1 to Day 36
Secondary outcomes:
measure: Neutralizing antibody titer at all pre-defined time points
timeFrame: Day 1, Day 22, Day 36, Day 78, Day 134, Day 202, Day 292 and Day 387
measure: Neutralizing antibody titer fold-rise post-vaccination at all pre-defined time points
timeFrame: Day 1, Day 22, Day 36, Day 78, Day 134, Day 202, Day 292 and Day 387
measure: Responders, as determined by neutralizing antibody titers at each pre-defined time point
timeFrame: Day 1, Day 22, Day 36, Day 78, Day 134, Day 202, Day 292 and Day 387
measure: 2-fold rise and 4-fold-rise in neutralization antibody titer at all pre-defined time points
timeFrame: Day 1, Day 22, Day 36, Day 78, Day 134, Day 202, Day 292 and Day 387
measure: Binding antibody fold-rise
timeFrame: Day 1, Day 22, Day 36, Day 78, Day 134, Day 202, Day 292 and Day 387
measure: Binding antibody concentrations
timeFrame: Day 1, Day 22, Day 36, Day 78, Day 134, Day 202, Day 292 and Day 387
measure: 2-fold-rise and 4-fold rise in binding antibody concentration
timeFrame: Day 1, Day 22, Day 36, Day 78, Day 134, Day 202, Day 292 and Day 387
measure: Responders, as determined by binding antibody concentrations
timeFrame: Day 1, Day 22, Day 36, Day 78, Day 134, Day 202, Day 292 and Day 387
measure: Occurrences of laboratory-confirmed symptomatic COVID-19
timeFrame: From Day 1 to Day 387
measure: Occurrences of symptomatic COVID-19 episodes associated with hospitalization
timeFrame: From Day 1 to Day 387
measure: Occurrences of severe symptomatic COVID-19
timeFrame: From Day 1 to Day 387
measure: Occurrences of death associated with symptomatic COVID-19
timeFrame: From Day 1 to Day 387
measure: Occurrences of serologically-confirmed SARS-CoV-2 infection
timeFrame: From Day 1 to Day 387
measure: Neutralizing antibody titer at all pre-defined time points post-booster and booster comparator injection
timeFrame: Day 1 and Day 15 (post-booster injection) and Day 36
measure: Neutralizing antibody titer fold-rise post-vaccination at all pre-defined time points post-booster and booster comparator injection
timeFrame: Day 1 and Day 15 (post-booster injection) and Day 36
measure: 2-fold rise and 4-fold-rise in neutralization antibody titer at all pre-defined time points post-booster and booster comparator injection
timeFrame: Day 1 and Day 15 -post-booster injection) and Day 36
measure: Seroresponse rate post-booster and booster comparator injection
timeFrame: Day 1 and Day 15 (post-booster injection) and Day 36
measure: Binding antibody concentrations post-booster injection
timeFrame: Day 1, Day 15, Day 29, Day 91, Day 181, and Day 366 (post-booster injection)
measure: Binding antibody fold-rise post-booster injection
timeFrame: Day 1, Day 15, Day 29, Day 91, Day 181, and Day 366 (post-booster injection)
measure: 2-fold-rise and 4-fold rise in binding antibody concentration post-booster injection
timeFrame: Day 1, Day 15, Day 29, Day 91, Day 181, and Day 366 (post-booster injection)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Synexus - Clinical Research Advantage, Inc. Site Number : 8400270
state: Alabama
city: Chandler
country: United States
facility: Synexus Chandler Site Number : 8400251
state: Arizona
city: Glendale
country: United States
facility: Synexus - Glendale. Site Number : 8400271
state: Arizona
city: Little Rock
country: United States
facility: Baptist Health Center for Clinical Research Site Number : 8400077
state: Arkansas
city: Los Angeles
country: United States
facility: Charles R. Drew University of Medicine and Science Site Number : 8400220
state: California
city: Rolling Hills Estates
country: United States
facility: Peninsula Research Associates, Inc. Site Number : 8400094
state: California
city: San Diego
country: United States
facility: Optimal Research Site Number : 8400173
state: California
city: New Haven
country: United States
facility: Yale University Site Number : 8400239
state: Connecticut
city: Washington
country: United States
facility: The George Washington University Site Number : 8400212
state: District of Columbia
city: Hollywood
country: United States
facility: Cenexel Research Centers of America Site Number : 8400089
state: Florida
city: Melbourne
country: United States
facility: Optimal Research, LLC Site Number : 8400057
state: Florida
city: Orlando
country: United States
facility: Synexus Clinical Research US, Inc. - Orlando Site Number : 8400179
state: Florida
city: Decatur
country: United States
facility: Emory University Decatur Site Number : 8400201
state: Georgia
city: Chicago
country: United States
facility: Chicago Clinical Research Institute, Inc. Site Number : 8400269
state: Illinois
city: Peoria
country: United States
facility: Optimal Research Site Number : 8400187
state: Illinois
city: Evansville
country: United States
facility: Synexus Clinical Research Evansville Site Number : 8400272
state: Indiana
city: New Orleans
country: United States
facility: Research Works INC Site Number : 8400045
state: Louisiana
city: Rockville
country: United States
facility: Optimal Research, LLC Rockville Site Number : 8400048
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital Site Number : 8400199
state: Massachusetts
city: Saint Louis
country: United States
facility: Synexus St. Louis Site Number : 8400100
state: Missouri
city: Omaha
country: United States
facility: Velocity Clinical Research, Omaha Site Number : 8400030
state: Nebraska
city: Teaneck
country: United States
facility: Holy Name Medical Center Site Number : 8400072
state: New Jersey
city: Brooklyn
country: United States
facility: NYU VC-Augustana Site Number : 8400267
state: New York
city: New York
country: United States
facility: New York University Langone Vaccine Center Site Number : 8400230
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center Site Number : 8400203
state: New York
city: Rochester
country: United States
facility: University of Rochester Site Number : 8400207
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh Site Number : 8400233
state: Pennsylvania
city: North Charleston
country: United States
facility: Coastal Carolina Research Center Site Number : 8400097
state: South Carolina
city: Rapid City
country: United States
facility: American Indian Clinical Trials Research Network Site Number : 8400204
state: South Dakota
city: Austin
country: United States
facility: AES Austin Site Number : 8400191
state: Texas
city: South Brisbane
country: Australia
facility: Investigational Site Number : 0360001
state: Queensland
city: Norwood
country: Australia
facility: Investigational Site Number : 0360003
city: Southport
country: Australia
facility: Investigational Site Number : 0360002
city: Westmead
country: Australia
facility: Investigational Site Number : 0360005
city: Woodville
country: Australia
facility: Investigational Site Number : 0360004
city: Dijon
country: France
facility: Investigational Site Number : 2500013
city: Limoges
country: France
facility: Investigational Site Number : 2500008
city: Lyon
country: France
facility: Investigational Site Number : 2500014
city: Marseille
country: France
facility: Investigational Site Number : 2500015
city: Marseille
country: France
facility: Investigational Site Number : 2500016
city: Nantes
country: France
facility: Investigational Site Number : 2500006
city: Paris
country: France
facility: Investigational Site Number : 2500005
city: Pessac
country: France
facility: Investigational Site Number : 2500003
city: Pierre Benite
country: France
facility: Investigational Site Number : 2500007
city: Rennes
country: France
facility: Investigational Site Number : 2500004
city: Tours Cedex 1
country: France
facility: Investigational Site Number : 2500002
city: Municipio Del Distrito Central
country: Honduras
facility: Investigational Site Number : 3400002
city: San Pedro Sula
country: Honduras
facility: Investigational Site Number : 3400001
city: New Lynn
country: New Zealand
facility: Investigational Site Number : 5540005
state: Auckland
city: Christchurch
country: New Zealand
facility: Investigational Site Number : 5540002
city: Nawton
country: New Zealand
facility: Investigational Site Number : 5540007
city: Nelson
country: New Zealand
facility: Investigational Site Number : 5540010
city: Rotorua
country: New Zealand
facility: Investigational Site Number : 5540001
city: Santiago De Compostela
country: Spain
facility: Investigational Site Number : 7240013
state: Galicia [Galicia]
city: Majadahonda
country: Spain
facility: Investigational Site Number : 7240016
state: Madrid
city: Madrid
country: Spain
facility: Investigational Site Number : 7240009
city: Valencia
country: Spain
facility: Investigational Site Number : 7240008
city: Vigo
country: Spain
facility: Investigational Site Number : 7240003
city: Runcorn
country: United Kingdom
facility: Investigational Site Number : 8260011
state: Halton
city: Bath
country: United Kingdom
facility: Investigational Site Number : 8260017
state: Somerset
city: Surrey
country: United Kingdom
facility: Investigational Site Number : 8260013
state: Sutton
city: Doncaster
country: United Kingdom
facility: Investigational Site Number : 8260014
city: Gloucester
country: United Kingdom
facility: Investigational Site Number : 8260016
city: Harrow
country: United Kingdom
facility: Investigational Site Number : 8260010
city: London
country: United Kingdom
facility: Investigational Site Number : 8260015
city: Southampton
country: United Kingdom
facility: Investigational Site Number : 8260012
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Sridhar S, Joaquin A, Bonaparte MI, Bueso A, Chabanon AL, Chen A, Chicz RM, Diemert D, Essink BJ, Fu B, Grunenberg NA, Janosczyk H, Keefer MC, Rivera M DM, Meng Y, Michael NL, Munsiff SS, Ogbuagu O, Raabe VN, Severance R, Rivas E, Romanyak N, Rouphael NG, Schuerman L, Sher LD, Walsh SR, White J, von Barbier D, de Bruyn G, Canter R, Grillet MH, Keshtkar-Jahromi M, Koutsoukos M, Lopez D, Masotti R, Mendoza S, Moreau C, Ceregido MA, Ramirez S, Said A, Tavares-Da-Silva F, Shi J, Tong T, Treanor J, Diazgranados CA, Savarino S. Safety and immunogenicity of an AS03-adjuvanted SARS-CoV-2 recombinant protein vaccine (CoV2 preS dTM) in healthy adults: interim findings from a phase 2, randomised, dose-finding, multicentre study. Lancet Infect Dis. 2022 May;22(5):636-648. doi: 10.1016/S1473-3099(21)00764-7. Epub 2022 Jan 25.