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

• Sponsor: Sanofi Pasteur, a Sanofi Company (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04904549
• Collaborator: (none)
• Enrollment: 23,726
• Locations: 94
• Arms: 4
• Anticipated Duration (Months): 29.9
• Patients Per Site: 252.4
• Patients Per Site Per Month: 8.4

Study Details

Study Description

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 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 + 6 months post-booster (ie, approximately 22 to 28 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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine (monovalent); Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine (bivalent); Biological: Placebo	Phase 3

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.

Initial, double-blind, primary series study design planned for 365 days post-last Initial injection (ie, approximately 386 days total) for each participant. Based on decisions of the Study OG, Stage 1 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 + 6 months post-booster (ie, approximately 22 to 28 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 23726 participants
• 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.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: For initial, double-blind, primary series design of study: 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. For crossover / booster design of study: unblinded
• Primary Purpose: Prevention
• 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
• Actual Study Start Date: Oct 14, 2020
• Anticipated Primary Completion Date: Apr 13, 2023
• Anticipated Study Completion Date: Apr 13, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Stage 1: SARS-CoV-2 vaccine 2 injections of monovalent SARS-CoV-2 vaccine at Day 1 and Day 22	Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine (monovalent); Pharmaceutical form: emulsion for injection. Route of administration: intramuscular injection
Placebo Comparator: Stage 1: Placebo 2 injections of placebo at Day 1 and Day 22	Biological: Placebo; Pharmaceutical form: liquid. Route of administration: intramuscular administration.
Experimental: Stage 2: SARS-CoV-2 vaccine 2 injections of bivalent SARS-CoV-2 vaccine at Day 1 and Day 22	Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine (bivalent); Pharmaceutical form: emulsion for injection. Route of administration: intramuscular injection.
Placebo Comparator: Stage 2: Placebo 2 injections of placebo at Day 1 and Day 22	Biological: Placebo; Pharmaceutical form: liquid. Route of administration: intramuscular administration.

Outcome Measures

Primary Outcome Measures

1. Occurrences of symptomatic COVID-19 [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.

2. Presence of solicited injection site or systemic reactions (collected in the reactogenicity subset) [Within 7 days after vaccination]

   Injection site reactions: injection site pain, erythema and swelling. Systemic reactions: fever, headache, malaise, myalgia, arthralgia and chills.

3. Presence of non-serious unsolicited adverse events (collected in the reactogenicity subset) [Within 21 days after vaccination]

   Adverse events other than solicited reactions.

4. Presence of immediate adverse events [Within 30 minutes after vaccination]

   Immediate adverse events include unsolicited injection site and systemic adverse events occurring within 30 minutes after injection.

5. Presence of medically attended adverse events [From Day 1 to Day 387]

   Medically attended adverse events will be assessed throughout the study.

6. Presence of serious adverse events [From Day 1 to Day 387]

   Serious adverse events will be assessed throughout the study.

7. Presence of adverse events of special interest [From Day 1 to Day 387]

   Adverse events of special interest will be assessed throughout the study.

8. Presence of virologically-confirmed SARS-CoV-2 infections and/or symptomatic COVID-19 [From Day 1 to Day 387]

   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.

Secondary Outcome Measures

1. Occurrences of SARS-CoV-2 infection [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.

2. Occurrence of severe COVID-19 [From ≥ 14 days after the second injection to Day 387]

3. Occurrences of asymptomatic SARS-CoV-2 infection [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.

4. Number of days with positive NAAT [From Day 1 to Day 387]

5. Viral copies/mL in respiratory samples [From Day 1 to Day 387]

6. Occurrences of positive NAAT in respiratory samples at each follow-up timepoint during symptomatic COVID-19 [From Day 1 to Day 387]

7. Occurrences of CDC-defined COVID-19 [From Day 1 to Day 387]

   Virologically-confirmed SARS-CoV-2 infection with at least one of CDC-defined clinical symptoms.

8. Occurrences of hospitalized COVID-19 [From Day 1 to Day 387]

   Hospitalized COVID-19 is defined as an episode of symptomatic COVID-19 that requires inpatient hospitalization.

9. Occurrences of symptomatic COVID-19 with severity of moderate COVID-19 or worse. [From Day 1 to Day 387]

   Composite endpoint of at least one of moderate or severe COVID-19.

10. Neutralizing antibody titer [Day 1, Day 22, Day 43, Day 78, Day 134, Day 202, Day 292, and Day 387]

11. Responders, as determined by neutralizing antibody titers [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

12. Neutralizing antibody titer fold-rise post-vaccination at all pre-defined time points [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.

13. 2-fold rise and 4-fold-rise in neutralization antibody titer at all pre-defined time points [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.

14. Severity of symptoms associated with symptomatic COVID-19 episode [From Day 1 to Day 387]

15. Occurrences of COVID-19 in each severity rating [From Day 1 to Day 387]

    COVID-19 severity score based on the ordinal scale of clinical assessment (7-point ordinal scale)

16. Death associated with COVID-19 [From Day 1 to day 387]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	AES - DRS - Simon Williamson Clinic, PC - Birmingham-Site Number:8400004	Birmingham	Alabama	United States	35211
2	Optimal Research Alabama-Site Number:8400019	Huntsville	Alabama	United States	35802
3	Peninsula Research Associates, Inc.-Site Number:8400021	Rolling Hills Estates	California	United States	90274
4	Synexus Clinical Research US, Inc.-Site Number:8400013	Centennial	Colorado	United States	80112
5	Optimal Research, LLC-Site Number:8400002	Melbourne	Florida	United States	32934
6	Synexus Clinical Research US, Inc. - Orlando-Site Number:8400020	Orlando	Florida	United States	32806
7	Synexus Research St Petersburg-Site Number:8400017	Pinellas Park	Florida	United States	33781
8	Synexus Clinical Research US, Inc. - Atlanta-Site Number:8400005	Atlanta	Georgia	United States	30328
9	Synexus Clinical Research Chicago-Site Number:8400012	Chicago	Illinois	United States	60602
10	Chicago Clinical Research Institute, Inc.-Site Number:8400026	Chicago	Illinois	United States	60607
11	Synexus Clinical Research Evansville-Site Number:8400008	Evansville	Indiana	United States	47714
12	Synexus St. Louis-Site Number:8400006	Saint Louis	Missouri	United States	63141
13	Synexus Clinical Research US, Inc. - Henderson-Site Number:8400018	Henderson	Nevada	United States	89052
14	Rochester Clinical Research, Inc.-Site Number:8400023	Rochester	New York	United States	14609
15	Synexus Akon-Site Number:8400009	Akron	Ohio	United States	44311
16	Synexus Clinical Research US, Inc. - Cincinnati-Site Number:8400010	Cincinnati	Ohio	United States	45236
17	Synexus US Columbus-Site Number:8400011	Columbus	Ohio	United States	43212
18	Synexus Clinical Research Anderson-Site Number:8400007	Anderson	South Carolina	United States	29621
19	Coastal Carolina Research Center-Site Number:8400022	Mount Pleasant	South Carolina	United States	29464
20	Black Hills Center for American Indian Health, Inc.-Site Number:8400025	Rapid City	South Dakota	United States	57701
21	Optimal Research Texas-Site Number:8400003	Austin	Texas	United States	78705
22	Synexus Dallas-Site Number:8400014	Dallas	Texas	United States	75231
23	Synexus Clinical Research US, Inc. - San Antonio-Site Number:8400015	San Antonio	Texas	United States	78229
24	Synexus Clinical Research Murray-Site Number:8400016	Murray	Utah	United States	84123
25	Investigational Site Number :1700010	Aguazul		Colombia
26	Investigational Site Number :1700002	Barranquilla		Colombia	080020
27	Investigational Site Number :1700008	Barranquilla		Colombia	080020
28	Investigational Site Number :1700001	Bogota		Colombia	111611
29	Investigational Site Number :1700005	Cali		Colombia	760002
30	Investigational Site Number :1700006	Chia		Colombia	0000
31	Investigational Site Number :1700004	Floridablanca		Colombia	681004
32	Investigational Site Number :1700007	Girardot		Colombia	00000
33	Investigational Site Number :1700009	Meta		Colombia	0000
34	Investigational Site Number :1700015	Quindio		Colombia	630001
35	Investigational Site Number :1700003	Soledad		Colombia	083001
36	Investigational Site Number :2880002	Kintampo		Ghana	P. O. Box 200
37	Investigational Site Number :2880003	Kumasi		Ghana	00000
38	Investigational Site Number :2880001	Navrongo		Ghana	114
39	Investigational Site Number :3400001	Municipio Del Distrito Central		Honduras	11101
40	Investigational Site Number :3400002	San Pedro Sula		Honduras	21104
41	Investigational Site Number :3560010	Ajmer		India	305001
42	Investigational Site Number :3560002	Ambawadi		India	380015
43	Investigational Site Number :3560007	Belgaum		India	590002
44	Investigational Site Number :3560001	Jaipur		India	302039
45	Investigational Site Number :3560005	Kanpur		India	208002
46	Investigational Site Number :3560009	Nagpur		India	440001
47	Investigational Site Number :3560011	Odisha		India	751003
48	Investigational Site Number :3560004	Patna		India	801507
49	Investigational Site Number :3560003	Punjagutta		India	500082
50	Investigational Site Number :3560006	Tamilnadu		India	603203
51	Investigational Site Number :3920005	Chiyoda-ku,	Tokyo	Japan	101-0041
52	Investigational Site Number :3920004	Haramachi,Shinjuku-ku	Tokyo	Japan	162-0053
53	Investigational Site Number :3920003	Kouenji minami,Suginami-ku	Tokyo	Japan	166-0003
54	Investigational Site Number :3920001	Kyobashi Chuo-ku	Tokyo	Japan	104-0031
55	Investigational Site Number :3920002	Ohta-ku	Tokyo	Japan	143-0015
56	Investigational Site Number :4040008	Mombasa	Washington	Kenya	80107 Ganjoni
57	Investigational Site Number :4040011	Butere		Kenya	50101
58	Investigational Site Number :4040006	Eldoret		Kenya	30100
59	Investigational Site Number :4040004	Kericho		Kenya	00200
60	Investigational Site Number :4040002	Kisumu		Kenya	40100
61	Investigational Site Number :4040003	Kisumu		Kenya	40100
62	Investigational Site Number :4040012	Kisumu		Kenya	40123 Kisumu
63	Investigational Site Number :4040001	Nairobi		Kenya	00100GPO
64	Investigational Site Number :4040007	Nairobi		Kenya	00100
65	Investigational Site Number :4040009	Thika		Kenya	00202 Kiambu
66	Investigational Site Number :4840009	Mexico City	Ciudad De Mexico	Mexico	04530
67	Investigational Site Number :4840005	Leon	Guanajuato	Mexico	37000
68	Investigational Site Number :4840004	Acapulco	Guerrero	Mexico	39670
69	Investigational Site Number :4840003	Guadalajara	Jalisco	Mexico	44280
70	Investigational Site Number :4840008	Cuernavaca	Morelos	Mexico	62290
71	Investigational Site Number :4840001	Durango		Mexico	34000
72	Investigational Site Number :4840006	Temixco		Mexico	62587
73	Investigational Site Number :4840002	Veracruz		Mexico	91910
74	Investigational Site Number :5240002	Dhulikhel		Nepal	45200
75	Investigational Site Number :5240003	Kathmandu		Nepal	44600
76	Investigational Site Number :5240001	Nepalgunj		Nepal	21900
77	Investigational Site Number :5660001	Abuja		Nigeria	900271
78	Investigational Site Number :1440002	Angoda		Sri Lanka	11010
79	Investigational Site Number :1440001	Ragama		Sri Lanka	11010
80	Investigational Site Number :8000002	Entebbe		Uganda	0
81	Investigational Site Number :8000005	Entebbe		Uganda	0
82	Investigational Site Number :8000001	Kampala		Uganda	0
83	Investigational Site Number :8000013	Kampala		Uganda	10101
84	Investigational Site Number :8000007	Kampala		Uganda	23491
85	Investigational Site Number :8000003	Kampala		Uganda	42 Nakasero Road
86	Investigational Site Number :8000004	Kampala		Uganda	Plot 101, Lubowa
87	Investigational Site Number :8000009	Kampala		Uganda
88	Investigational Site Number :8000014	Lira		Uganda	10101
89	Investigational Site Number :8000006	Tororo		Uganda	0000
90	Investigational Site Number :8040002	Kiev		Ukraine	04210
91	Investigational Site Number :8040004	Kyiv		Ukraine	01023
92	Investigational Site Number :8040003	Kyiv		Ukraine	02002
93	Investigational Site Number :8040001	Kyiv		Ukraine	03037
94	Investigational Site Number :8040005	Vinnytsia		Ukraine	21050

Sponsors and Collaborators

• Sanofi Pasteur, a Sanofi Company

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT04904549
• Other Study ID Numbers: VAT00008; U1111-1264-3238
• First Posted: May 27, 2021
• Last Update Posted: Jul 27, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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
• Additional relevant MeSH terms: COVID-19; Vaccines

Study Results

No Results Posted as of Jul 27, 2022