Clinical trial NCT04904549: Study of Monovalent and Bivalent Recombinant Protein Vaccines Against COVID-19 in Adults 18 Years of Age and Older
Official title: 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 as a Primary Series and Open-label Extension to Assess Immunogenicity, Safety, Efficacy of a Monovalent Booster Dose of SARS-CoV2 Adjuvanted Recombinant Protein Vaccine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2021-05-27
Enrollment: 23726
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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, the bivalent vaccine will be assessed against a placebo control.
Primary purpose: PREVENTION

Brief summary: The purpose of this Phase III study is to assess the efficacy, safety, and immunogenicity of two CoV2 preS dTM-AS03 vaccines (monovalent and bivalent) as part of primary series vaccinations in a multi-stage approach, as well as a booster injection of a CoV2 preS dTM-AS03 vaccine, in adults 18 years of age and older.

A total of approximately 21 046 participants are planned to be enrolled (5080 per study intervention group in Stage 1 and 5443 per study intervention group in Stage 2).

Initial, double-blind, primary series study design is planned for 365 days post-last Initial injection (ie, approximately 386 days total) for each participant.

Based on decisions of the Study Oversight Group, Stage 1 and Stage 2 participants will be invited to participate in an unblinded Crossover / Booster study design with duration as follows:

* For participants who initially received vaccine: 12 months post-booster (ie, approximately 18 to 24 months)
* For participants who initially received placebo: ≥ 4 months post-last dose of the primary series + 12 months post-booster (ie, approximately 28 to 34 months)
* For participants who do not consent to continue in the unblinded Crossover / Booster part of the study, all study procedures will be stopped and participants will be discontinued from the study.

Detailed description: The duration of participation in the initial, double-blind, primary series design of the study will be approximately 365 days post-last injection (ie, approximately 386 days total) for each participant.

Based on decisions of the Study OG, Stage 1 and Stage 2 participants will be invited to participate in an unblinded Crossover / Booster study design with duration as follows:

* For participants who initially received vaccine: 12 months post-booster (ie, approximately 18 to 24 months)
* For participants who initially received placebo: ≥ 4 months post-last dose of the primary series + 12 months post-booster (ie, approximately 28 to 34 months)
* For participants who do not consent to continue in the unblinded Crossover / Booster part of the study, all study procedures will be stopped and participants will be discontinued from the study.

Eligibility criteria: 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.
* Informed consent form has been signed and dated
* Able to attend all visits and to comply with all study procedures
* Covered by health insurance, only if required by local, regional or national regulations
* 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) within 25 hours before any dose of study intervention.

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 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.
* Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
* Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (ie, parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study.
* 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.

Primary outcomes:
measure: Occurrences of symptomatic COVID-19
timeFrame: From ≥ 14 days after the second injection to Day 387
measure: Presence of solicited injection site or systemic reactions (collected in the reactogenicity subset)
timeFrame: Within 7 days after vaccination
measure: Presence of non-serious unsolicited adverse events (collected in the reactogenicity subset)
timeFrame: Within 21 days after vaccination
measure: Presence of immediate adverse events
timeFrame: Within 30 minutes after vaccination
measure: Presence of medically attended adverse events
timeFrame: From Day 1 to Day 387
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 virologically-confirmed SARS-CoV-2 infections and/or symptomatic COVID-19
timeFrame: From Day 1 to Day 387
Secondary outcomes:
measure: Occurrences of SARS-CoV-2 infection
timeFrame: From ≥ 14 days after the second injection to Day 387
measure: Occurrence of severe COVID-19
timeFrame: From ≥ 14 days after the second injection to Day 387
measure: Occurrences of asymptomatic SARS-CoV-2 infection
timeFrame: From Day 1 to Day 387
measure: Number of days with positive NAAT
timeFrame: From Day 1 to Day 387
measure: Viral copies/mL in respiratory samples
timeFrame: From Day 1 to Day 387
measure: Occurrences of positive NAAT in respiratory samples at each follow-up timepoint during symptomatic COVID-19
timeFrame: From Day 1 to Day 387
measure: Occurrences of CDC-defined COVID-19
timeFrame: From Day 1 to Day 387
measure: Occurrences of hospitalized COVID-19
timeFrame: From Day 1 to Day 387
measure: Occurrences of symptomatic COVID-19 with severity of moderate COVID-19 or worse.
timeFrame: From Day 1 to Day 387
measure: Neutralizing antibody titer
timeFrame: Day 1, Day 22, Day 43, Day 78, Day 134, Day 202, Day 292, and Day 387
measure: Responders, as determined by neutralizing antibody titers
timeFrame: Day 1, Day 22, Day 43, 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 43, 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 43, Day 78, Day 134, Day 202, Day 292, and Day 387
measure: Severity of symptoms associated with symptomatic COVID-19 episode
timeFrame: From Day 1 to Day 387
measure: Occurrences of COVID-19 in each severity rating
timeFrame: From Day 1 to Day 387
measure: Death associated with COVID-19
timeFrame: From Day 1 to day 387
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: AES - DRS - Simon Williamson Clinic, PC - Birmingham Site Number : 8400004
state: Alabama
city: Huntsville
country: United States
facility: Optimal Research Alabama Site Number : 8400019
state: Alabama
city: Rolling Hills Estates
country: United States
facility: Peninsula Research Associates, Inc. Site Number : 8400021
state: California
city: Centennial
country: United States
facility: Synexus Clinical Research US, Inc. Site Number : 8400013
state: Colorado
city: Melbourne
country: United States
facility: Optimal Research, LLC Site Number : 8400002
state: Florida
city: Orlando
country: United States
facility: Synexus Clinical Research US, Inc. - Orlando Site Number : 8400020
state: Florida
city: Pinellas Park
country: United States
facility: AES St. Petersburg Site Number : 8400017
state: Florida
city: Atlanta
country: United States
facility: Synexus Clinical Research US, Inc. - Atlanta Site Number : 8400005
state: Georgia
city: Chicago
country: United States
facility: Synexus Clinical Research Chicago Site Number : 8400012
state: Illinois
city: Evansville
country: United States
facility: Synexus Clinical Research Evansville Site Number : 8400008
state: Indiana
city: Saint Louis
country: United States
facility: Synexus St. Louis Site Number : 8400006
state: Missouri
city: Henderson
country: United States
facility: Synexus Clinical Research US, Inc. - Henderson Site Number : 8400018
state: Nevada
city: Rochester
country: United States
facility: Rochester Clinical Research, Inc. Site Number : 8400023
state: New York
city: Akron
country: United States
facility: Synexus Akron Site Number : 8400009
state: Ohio
city: Cincinnati
country: United States
facility: Synexus Clinical Research US, Inc. - Cincinnati Site Number : 8400010
state: Ohio
city: Columbus
country: United States
facility: Synexus US Columbus Site Number : 8400011
state: Ohio
city: Anderson
country: United States
facility: Synexus Clinical Research Anderson Site Number : 8400007
state: South Carolina
city: North Charleston
country: United States
facility: Coastal Carolina Research Center - N Charleston Site Number : 8400022
state: South Carolina
city: Rapid City
country: United States
facility: American Indian Clinical Trials Research Network Site Number : 8400025
state: South Dakota
city: Austin
country: United States
facility: AES Austin Site Number : 8400003
state: Texas
city: Dallas
country: United States
facility: Synexus Dallas Site Number : 8400014
state: Texas
city: San Antonio
country: United States
facility: Synexus Clinical Research US, Inc. - San Antonio Site Number : 8400015
state: Texas
city: Murray
country: United States
facility: AES Salt Lake City Site Number : 8400016
state: Utah
city: Aguazul
country: Colombia
facility: Investigational Site Number : 1700010
city: Barranquilla
country: Colombia
facility: Investigational Site Number : 1700002
city: Barranquilla
country: Colombia
facility: Investigational Site Number : 1700008
city: Bogota
country: Colombia
facility: Investigational Site Number : 1700001
city: Cali
country: Colombia
facility: Investigational Site Number : 1700005
city: Chia
country: Colombia
facility: Investigational Site Number : 1700006
city: Floridablanca
country: Colombia
facility: Investigational Site Number : 1700004
city: Girardot
country: Colombia
facility: Investigational Site Number : 1700007
city: Meta
country: Colombia
facility: Investigational Site Number : 1700009
city: Quindio
country: Colombia
facility: Investigational Site Number : 1700015
city: Soledad
country: Colombia
facility: Investigational Site Number : 1700003
city: Kintampo
country: Ghana
facility: Investigational Site Number : 2880002
city: Kumasi
country: Ghana
facility: Investigational Site Number : 2880003
city: Navrongo
country: Ghana
facility: Investigational Site Number : 2880001
city: Municipio Del Distrito Central
country: Honduras
facility: Investigational Site Number : 3400001
city: San Pedro Sula
country: Honduras
facility: Investigational Site Number : 3400002
city: Ajmer
country: India
facility: Investigational Site Number : 3560010
city: Ambawadi
country: India
facility: Investigational Site Number : 3560002
city: Belgaum
country: India
facility: Investigational Site Number : 3560007
city: Jaipur
country: India
facility: Investigational Site Number : 3560001
city: Kanpur
country: India
facility: Investigational Site Number : 3560005
city: Nagpur
country: India
facility: Investigational Site Number : 3560009
city: Odisha
country: India
facility: Investigational Site Number : 3560011
city: Patna
country: India
facility: Investigational Site Number : 3560004
city: Punjagutta
country: India
facility: Investigational Site Number : 3560003
city: Tamilnadu
country: India
facility: Investigational Site Number : 3560006
city: Chiyoda-ku,
country: Japan
facility: Investigational Site Number : 3920005
state: Tokyo
city: Haramachi,Shinjuku-ku
country: Japan
facility: Investigational Site Number : 3920004
state: Tokyo
city: Kouenji minami,Suginami-ku
country: Japan
facility: Investigational Site Number : 3920003
state: Tokyo
city: Kyobashi Chuo-ku
country: Japan
facility: Investigational Site Number : 3920001
state: Tokyo
city: Ohta-ku
country: Japan
facility: Investigational Site Number : 3920002
state: Tokyo
city: Butere
country: Kenya
facility: Investigational Site Number : 4040011
city: Eldoret
country: Kenya
facility: Investigational Site Number : 4040006
city: Kericho
country: Kenya
facility: Investigational Site Number : 4040004
city: Kisumu
country: Kenya
facility: Investigational Site Number : 4040002
city: Kisumu
country: Kenya
facility: Investigational Site Number : 4040003
city: Kisumu
country: Kenya
facility: Investigational Site Number : 4040012
city: Mombasa
country: Kenya
facility: Investigational Site Number : 4040008
city: Nairobi
country: Kenya
facility: Investigational Site Number : 4040001
city: Nairobi
country: Kenya
facility: Investigational Site Number : 4040007
city: Thika
country: Kenya
facility: Investigational Site Number : 4040009
city: Mexico City
country: Mexico
facility: Investigational Site Number : 4840009
state: Ciudad De Mexico
city: Leon
country: Mexico
facility: Investigational Site Number : 4840005
state: Guanajuato
city: Acapulco
country: Mexico
facility: Investigational Site Number : 4840004
state: Guerrero
city: Guadalajara
country: Mexico
facility: Investigational Site Number : 4840003
state: Jalisco
city: Cuernavaca
country: Mexico
facility: Investigational Site Number : 4840008
state: Morelos
city: Temixco
country: Mexico
facility: Investigational Site Number : 4840006
city: Veracruz
country: Mexico
facility: Investigational Site Number : 4840002
city: Dhulikhel
country: Nepal
facility: Investigational Site Number : 5240002
city: Kathmandu
country: Nepal
facility: Investigational Site Number : 5240003
city: Nepalgunj
country: Nepal
facility: Investigational Site Number : 5240001
city: Entebbe
country: Uganda
facility: Investigational Site Number : 8000002
city: Entebbe
country: Uganda
facility: Investigational Site Number : 8000005
city: Kampala
country: Uganda
facility: Investigational Site Number : 8000001
city: Kampala
country: Uganda
facility: Investigational Site Number : 8000013
city: Kampala
country: Uganda
facility: Investigational Site Number : 8000007
city: Kampala
country: Uganda
facility: Investigational Site Number : 8000003
city: Kampala
country: Uganda
facility: Investigational Site Number : 8000004
city: Lira
country: Uganda
facility: Investigational Site Number : 8000014
city: Kiev
country: Ukraine
facility: Investigational Site Number : 8040002
city: Kyiv
country: Ukraine
facility: Investigational Site Number : 8040004
city: Kyiv
country: Ukraine
facility: Investigational Site Number : 8040003
city: Kyiv
country: Ukraine
facility: Investigational Site Number : 8040001
Study officials:
References: