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

COVID-19 Clinical Trial

— VAT00008  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04904549
• Other study ID #: VAT00008
• Secondary ID: U1111-1264-3238
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: May 26, 2021
• Est. completion date: January 31, 2025

Study information

• Verified date: January 2023
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 23726
• Est. completion date: January 31, 2025
• Est. primary completion date: January 31, 2025
• 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.
• 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.

Related Conditions & MeSH terms

• COVID-19

Intervention

Biological:
• SARS-CoV-2 adjuvanted recombinant protein vaccine (monovalent D614) (primary series)
Pharmaceutical form: emulsion for injection. Route of administration: intramuscular injection
• SARS-CoV-2 adjuvanted recombinant protein vaccine (bivalent D614 + B.1.351) (primary series)
Pharmaceutical form: emulsion for injection. Route of administration: intramuscular injection.
• Placebo
Pharmaceutical form: liquid. Route of administration: intramuscular administration.
• SARS-CoV-2 adjuvanted recombinant protein vaccine (monovalent B.1.351) (booster dose) >= 4 months after last vaccination
Pharmaceutical form: emulsion for injection. Route of administration: intramuscular injection.
• SARS-CoV-2 adjuvanted recombinant protein vaccine(monovalent D614)(primary series)& SARS-CoV-2 adjuvanted recombinant protein vaccine(monovalent B.1.351)(booster dose)>=4 months after last vaccination
Pharmaceutical form: emulsion for injection. Route of administration: intramuscular injection.

Locations

Country	Name	City	State
Colombia	Investigational Site Number :1700010	Aguazul
Colombia	Investigational Site Number :1700002	Barranquilla
Colombia	Investigational Site Number :1700008	Barranquilla
Colombia	Investigational Site Number :1700001	Bogota
Colombia	Investigational Site Number :1700005	Cali
Colombia	Investigational Site Number :1700006	Chia
Colombia	Investigational Site Number :1700004	Floridablanca
Colombia	Investigational Site Number :1700007	Girardot
Colombia	Investigational Site Number :1700009	Meta
Colombia	Investigational Site Number :1700015	Quindio
Colombia	Investigational Site Number :1700003	Soledad
Ghana	Investigational Site Number :2880002	Kintampo
Ghana	Investigational Site Number :2880003	Kumasi
Ghana	Investigational Site Number :2880001	Navrongo
Honduras	Investigational Site Number :3400001	Municipio Del Distrito Central
Honduras	Investigational Site Number :3400002	San Pedro Sula
India	Investigational Site Number :3560010	Ajmer
India	Investigational Site Number :3560002	Ambawadi
India	Investigational Site Number :3560007	Belgaum
India	Investigational Site Number :3560001	Jaipur
India	Investigational Site Number :3560005	Kanpur
India	Investigational Site Number :3560009	Nagpur
India	Investigational Site Number :3560011	Odisha
India	Investigational Site Number :3560004	Patna
India	Investigational Site Number :3560003	Punjagutta
India	Investigational Site Number :3560006	Tamilnadu
Japan	Investigational Site Number :3920005	Chiyoda-ku,	Tokyo
Japan	Investigational Site Number :3920004	Haramachi,Shinjuku-ku	Tokyo
Japan	Investigational Site Number :3920003	Kouenji minami,Suginami-ku	Tokyo
Japan	Investigational Site Number :3920001	Kyobashi Chuo-ku	Tokyo
Japan	Investigational Site Number :3920002	Ohta-ku	Tokyo
Kenya	Investigational Site Number :4040011	Butere
Kenya	Investigational Site Number :4040006	Eldoret
Kenya	Investigational Site Number :4040004	Kericho
Kenya	Investigational Site Number :4040002	Kisumu
Kenya	Investigational Site Number :4040003	Kisumu
Kenya	Investigational Site Number :4040012	Kisumu
Kenya	Investigational Site Number :4040008	Mombasa	Washington
Kenya	Investigational Site Number :4040001	Nairobi
Kenya	Investigational Site Number :4040007	Nairobi
Kenya	Investigational Site Number :4040009	Thika
Mexico	Investigational Site Number :4840004	Acapulco	Guerrero
Mexico	Investigational Site Number :4840008	Cuernavaca	Morelos
Mexico	Investigational Site Number :4840001	Durango
Mexico	Investigational Site Number :4840003	Guadalajara	Jalisco
Mexico	Investigational Site Number :4840005	Leon	Guanajuato
Mexico	Investigational Site Number :4840009	Mexico City	Ciudad De Mexico
Mexico	Investigational Site Number :4840006	Temixco
Mexico	Investigational Site Number :4840002	Veracruz
Nepal	Investigational Site Number :5240002	Dhulikhel
Nepal	Investigational Site Number :5240003	Kathmandu
Nepal	Investigational Site Number :5240001	Nepalgunj
Nigeria	Investigational Site Number :5660001	Abuja
Sri Lanka	Investigational Site Number :1440002	Angoda
Sri Lanka	Investigational Site Number :1440001	Ragama
Uganda	Investigational Site Number :8000002	Entebbe
Uganda	Investigational Site Number :8000005	Entebbe
Uganda	Investigational Site Number :8000001	Kampala
Uganda	Investigational Site Number :8000003	Kampala
Uganda	Investigational Site Number :8000004	Kampala
Uganda	Investigational Site Number :8000007	Kampala
Uganda	Investigational Site Number :8000009	Kampala
Uganda	Investigational Site Number :8000013	Kampala
Uganda	Investigational Site Number :8000014	Lira
Uganda	Investigational Site Number :8000006	Tororo
Ukraine	Investigational Site Number :8040002	Kiev
Ukraine	Investigational Site Number :8040001	Kyiv
Ukraine	Investigational Site Number :8040003	Kyiv
Ukraine	Investigational Site Number :8040004	Kyiv
Ukraine	Investigational Site Number :8040005	Vinnytsia
United States	Synexus Akon-Site Number:8400009	Akron	Ohio
United States	Synexus Clinical Research Anderson-Site Number:8400007	Anderson	South Carolina
United States	Synexus Clinical Research US, Inc. - Atlanta-Site Number:8400005	Atlanta	Georgia
United States	Optimal Research Texas-Site Number:8400003	Austin	Texas
United States	AES - DRS - Simon Williamson Clinic, PC - Birmingham-Site Number:8400004	Birmingham	Alabama
United States	Synexus Clinical Research US, Inc.-Site Number:8400013	Centennial	Colorado
United States	Chicago Clinical Research Institute, Inc.-Site Number:8400026	Chicago	Illinois
United States	Synexus Clinical Research Chicago-Site Number:8400012	Chicago	Illinois
United States	Synexus Clinical Research US, Inc. - Cincinnati-Site Number:8400010	Cincinnati	Ohio
United States	Synexus US Columbus-Site Number:8400011	Columbus	Ohio
United States	Synexus Dallas-Site Number:8400014	Dallas	Texas
United States	Synexus Clinical Research Evansville-Site Number:8400008	Evansville	Indiana
United States	Synexus Clinical Research US, Inc. - Henderson-Site Number:8400018	Henderson	Nevada
United States	Optimal Research Alabama-Site Number:8400019	Huntsville	Alabama
United States	Optimal Research, LLC-Site Number:8400002	Melbourne	Florida
United States	Coastal Carolina Research Center-Site Number:8400022	Mount Pleasant	South Carolina
United States	Synexus Clinical Research Murray-Site Number:8400016	Murray	Utah
United States	Synexus Clinical Research US, Inc. - Orlando-Site Number:8400020	Orlando	Florida
United States	Synexus Research St Petersburg-Site Number:8400017	Pinellas Park	Florida
United States	Black Hills Center for American Indian Health, Inc.-Site Number:8400025	Rapid City	South Dakota
United States	Rochester Clinical Research, Inc.-Site Number:8400023	Rochester	New York
United States	Peninsula Research Associates, Inc.-Site Number:8400021	Rolling Hills Estates	California
United States	Synexus St. Louis-Site Number:8400006	Saint Louis	Missouri
United States	Synexus Clinical Research US, Inc. - San Antonio-Site Number:8400015	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi Pasteur, a Sanofi Company

Countries where clinical trial is conducted

United States,  Colombia,  Ghana,  Honduras,  India,  Japan,  Kenya,  Mexico,  Nepal,  Nigeria,  Sri Lanka,  Uganda,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrences of symptomatic COVID-19	Symptomatic COVID-19 is defined as virologically-confirmed SARS-CoV-2 infection accompanied by protocol-defined COVID-19-like illness.	From = 14 days after the second injection to Day 387
Primary	Presence of solicited injection site or systemic reactions (collected in the reactogenicity subset)	Injection site reactions: injection site pain, erythema and swelling. Systemic reactions: fever, headache, malaise, myalgia, arthralgia and chills.	Within 7 days after vaccination
Primary	Presence of non-serious unsolicited adverse events (collected in the reactogenicity subset)	Adverse events other than solicited reactions.	Within 21 days after vaccination
Primary	Presence of immediate adverse events	Immediate adverse events include unsolicited injection site and systemic adverse events occurring within 30 minutes after injection.	Within 30 minutes after vaccination
Primary	Presence of medically attended adverse events	Medically attended adverse events will be assessed throughout the study.	From Day 1 to Day 387
Primary	Presence of serious adverse events	Serious adverse events will be assessed throughout the study.	From Day 1 to Day 387
Primary	Presence of adverse events of special interest	Adverse events of special interest will be assessed throughout the study.	From Day 1 to Day 387
Primary	Presence of virologically-confirmed SARS-CoV-2 infections and/or symptomatic COVID-19	Percentage of participants with positive result for SARSCoV-2 infection by Nucleic Acid Amplification Test (NAAT) on at least one respiratory sample accompanied or not by protocol-defined clinical COVID-19 symptoms.	From Day 1 to Day 387
Secondary	Occurrences of SARS-CoV-2 infection	SARS-CoV-2 infection is defined as a serologically-confirmed SARS-CoV-2 infection or virologically-confirmed SARS-CoV-2 infection.	From = 14 days after the second injection to Day 387
Secondary	Occurrence of severe COVID-19		From = 14 days after the second injection to Day 387
Secondary	Occurrences of asymptomatic SARS-CoV-2 infection	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.	From Day 1 to Day 387
Secondary	Number of days with positive NAAT		From Day 1 to Day 387
Secondary	Viral copies/mL in respiratory samples		From Day 1 to Day 387
Secondary	Occurrences of positive NAAT in respiratory samples at each follow-up timepoint during symptomatic COVID-19		From Day 1 to Day 387
Secondary	Occurrences of CDC-defined COVID-19	Virologically-confirmed SARS-CoV-2 infection with at least one of CDC-defined clinical symptoms.	From Day 1 to Day 387
Secondary	Occurrences of hospitalized COVID-19	Hospitalized COVID-19 is defined as an episode of symptomatic COVID-19 that requires inpatient hospitalization.	From Day 1 to Day 387
Secondary	Occurrences of symptomatic COVID-19 with severity of moderate COVID-19 or worse.	Composite endpoint of at least one of moderate or severe COVID-19.	From Day 1 to Day 387
Secondary	Neutralizing antibody titer		Day 1, Day 22, Day 43, Day 78, Day 134, Day 202, Day 292, and Day 387
Secondary	Responders, as determined by neutralizing antibody titers	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	Day 1, Day 22, Day 43, 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 43, 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 43, Day 78, Day 134, Day 202, Day 292, and Day 387
Secondary	Severity of symptoms associated with symptomatic COVID-19 episode		From Day 1 to Day 387
Secondary	Occurrences of COVID-19 in each severity rating	COVID-19 severity score based on the ordinal scale of clinical assessment (7-point ordinal scale)	From Day 1 to Day 387
Secondary	Death associated with COVID-19		From Day 1 to day 387