Study of GRAd-COV2 for the Prevention of COVID-19 in Adults

Covid19 Clinical Trial

— COVITAR  

Official title:

A Phase II/III, Randomized, Stratified, Observer-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of GRAd-COV2 Vaccine in Adults Aged 18 Years and Older

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04791423
• Other study ID #: RT-CoV-2_01
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: March 15, 2021
• Est. completion date: May 13, 2022

Study information

• Verified date: May 2022
• Source: ReiThera Srl
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Multicenter Study assessing the safety, efficacy, and immunogenicity of the candidate vaccine GRAd-COV2, compared to placebo, for the prevention of COVID-19. Participants will be adults ≥ 18 years of age who are healthy or have medically stable chronic diseases and are at increased risk for SARS-CoV-2 acquisition and COVID-19. In the phase II part approximately 900 participants will be randomized in a 1:1:1 ratio to receive i) 2 repeated (21 days apart) intramuscular (IM) doses of GRAd-COV2 at 1x10^11 viral particle (vp) (n = approximately 300 subjects) ii) 1 single IM dose of GRAd-COV2 at 2x10^11 vp plus 1 dose of placebo after 21 days (n= approximately 300 subject) or 2 doses of placebo (n = approximately 300 subjects) on day 1 and day 22. There will be 3 strata for randomization: ≥ 65 years, < 65 years and categorized to be at increased risk ("at risk") for the complications of COVID-19, and < 65 years "not at risk". Risk will be defined referring to the study participants' relevant past and current medical history. An independent Data Safety Monitoring Board will provide oversight, to ensure safe and ethical conduct of the Study; a Steering Committee will revise safety data (collected for 900 participants 1 week after dosing) and immunogenicity data (collected for 450 participants 5 weeks after the first dosing) generated in phase II part. Jointly DSMB and SC will recommend the expansion to phase III and the best regimen to be used.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10300
• Est. completion date: May 13, 2022
• Est. primary completion date: June 4, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adult female and male, = 18 years of age at the time of consent

2. Medically stable such that, according to the judgment of the investigator, hospitalization within the study period is not anticipated and the participant appears likely to be able to remain on study through the end of protocol-specified follow-up. A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months prior to enrollment

3. Able to understand and comply with study requirements/procedures based on the assessment of the investigator

4. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies

5. Female participants, (a) Women of childbearing potential must: Have a negative pregnancy test on the day of screening and on Day 1; use one highly effective form of birth control for at least 28 days prior to Day 1 and agree to continue using one highly effective form of birth control through 60 days following administration of study intervention.

6. Capable of giving signed informed consent.

Exclusion Criteria:

1. History of allergy to any component of the vaccine

2. History of Guillain-Barré syndrome or any other demyelinating condition

3. Significant infection or other acute illness, including fever > 37.3 °C on the day prior to or day of randomization

4. History of laboratory-confirmed SARS-CoV-2 infection

5. Any confirmed or suspected immunosuppressive or immunodeficient state, including asplenia (only for phase II)

6. Recurrent severe infections and use of immunosuppressant medication within the past 6 months

7. History of primary malignancy except for: (a) Malignancy with low potential risk for recurrence after curative treatment (for example, history of childhood leukaemia) or metastasis (for example, indolent prostate cancer) in the opinion of the site investigator. (b) Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease (c) Adequately treated uterine cervical carcinoma in situ without evidence of disease (d) Localized prostate cancer (only for phase II)

8. Clinically significant bleeding disorder (eg, factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following IM injections or vene puncture

9. Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, and neurological illness, as judged by the Investigator (mild/moderate well-controlled comorbidities are allowed) (only for phase II)

10. Any other significant disease, disorder, or finding that may significantly increase the risk to the participant because of participation in the study, affect the ability of the participant to participate in the study, or impair interpretation of the study data

11. Receipt of, or planned receipt of investigational or licensed products indicated for the treatment or prevention of SARS-CoV-2 or COVID-19

12. Receipt of any vaccine (licensed or investigational) other than licensed influenza vaccines within 30 days prior to and after administration of study intervention

13. Receipt of immunoglobulins and/or any blood products within 3 months prior to administration of study intervention or expected receipt during the period of study follow-up

14. Involvement in the planning and/or conduct of this study (applies to both Sponsor staff and/or staff at the study site)

15. For women only - currently pregnant (confirmed with positive pregnancy test) or breast-feeding

16. Has donated = 450 mL of blood products within 30 days prior to randomization or expects to donate blood within 90 days of administration of study intervention.

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

Biological:
• GRAd-COV2
GRAd-COV2 is a replication-defective gorilla adenoviral vector (GRAd) encoding the SARS-CoV-2 surface glycoprotein (S, Spike) antigen under the control of CMV immediate early promoter. The encoded Spike antigen is stabilized in pre-fusion conformation by introducing 2 proline residues

Other:
• Placebo
Saline solution

Locations

Country	Name	City	State
Italy	Azienda Ospedaliera San Giuseppe Moscati	Avellino
Italy	Ospedale Vittorio Emanuele Ii	Bisceglie	Barletta- Andria-Trani
Italy	A.O. Sant'Anna E San Sebastiano Caserta	Caserta
Italy	Asst Di Cremona	Cremona
Italy	Azienda Ospedaliero-Universitaria Di Ferrara	Ferrara
Italy	Ao Ospedali Riuniti - Foggia	Foggia
Italy	E.O. Ospedali Galliera	Genova
Italy	Presidio Ospedaliero Nord-Ospedale Santa Maria Goretti Latina	Latina
Italy	Asst Fatebenefratelli Sacco	Milano
Italy	Fondaz.Irccs Ca' Granda - Ospedale Maggiore Policlinico	Milano
Italy	Ospedale S.Gerardo - Monza	Monza
Italy	Azienda Ospedaliera Dei Colli - P Cotugno	Napoli
Italy	Azienda Ospedaliera Universitaria Della Universita' Vanvitelli I Di Napoli	Napoli
Italy	Az.Osp.Univ.P.Giaccone	Palermo
Italy	Azienda Ospedaliero-Universitaria Di Parma	Parma
Italy	Policlinico S. Matteo - Pavia	Pavia
Italy	Azienda Usl Di Piacenza	Piacenza
Italy	Azienda Ospedaliero-Universitaria Pisana	Pisa
Italy	Azienda Ospedaliera Policlinico Umberto I	Roma
Italy	Istituto per le Malattie Infettive Lazzaro Spallanzani IRCCS	Roma	RM
Italy	Policlinico A. Gemelli E C.I.C.- Policlinico Universitario A. Gemelli	Roma
Italy	Ospedale Amedeo Di Savoia	Torino
Italy	Azienda Sanitaria Universitaria Integrata Di Trieste	Trieste
Italy	Asst Dei Sette Laghi	Varese
Italy	Ospedale Unico Del Vercellese - Ospedale Sant'Andrea	Vercelli
Italy	Centro Ricerche Cliniche Di Verona Srl	Verona

Sponsors (2)

Lead Sponsor	Collaborator
ReiThera Srl	Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with symptomatic laboratory confirmed COVID-19	A binary response, whereby a participant is defined as a COVID-19 case if their first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurs = 28 days post first dose or = 7 days after the second dose of study intervention (depending on the selected regimen).	FROM > 28 DAYS POST FIRST DOSE (DAY 1) UP TO DAY 360
Primary	Incidence of AEs, SAEs, MAAEs, and AESI	Incidence of AEs for 28 days post each dose of study intervention.; Incidence of SAEs, MAAEs, and AESIs from Day 1 post treatment through Day 360.	28 DAYS POST EACH DOSE FOR AEs and FROM RANDOMIZATION UP TO DAY 360 FOR SAEs, MAAEs, and AESI
Primary	Incidence of local and systemic solicited AEs	Incidence of local and systemic solicited AEs	7 DAYS POST EACH DOSE OF STUDY INTERVENTION
Primary	Post-treatment GMTs in SARS-CoV2 S and/or RBD antibodies	Post-treatment GMTs from day of dosing baseline value to 35 days post first dose in SARS-CoV-2 S and/or RBD antibodies.	from day 1 to day 36
Primary	Post-treatment GMFRs in SARS-CoV2 S and/or RBD antibodies	Post-treatment GMFRs from day of dosing baseline value to 35 days post first dose in SARS-CoV-2 S and/or RBD antibodies.	from day 1 to day 36
Primary	Proportion of participants with post-treatment seroresponse (> 4-fold rise in titers) to the S and/or RBD antigens of GRAd-COV2	Proportion of participants with post-treatment seroresponse (> 4-fold rise in titers) to the S and/or RBD antigens of GRAd-COV2.	from day 1 to day 36
Secondary	Time to first SARS-CoV2 RT-PCR positive severe or critical symptomatic illness	Time to first SARS-CoV-2 RT-PCR-positive severe or critical symptomatic illness occurring = 28 days post first dose or = 7 days after second dose of study intervention	FROM > 28 DAYS POST FIRST DOSE (DAY 1) UP TO DAY 360
Secondary	Proportion of participants who have a post-treatment response for SARS-COV2 Nucleocapside antibodies	Proportion of participants who have a post-treatment response (negative at baseline to positive post treatment with study intervention) for SARS-CoV-2 Nucleocapsid antibodies over time.	from Day 1 up to day 360
Secondary	Time to first case of SARS-COV2 RT-PCR positive symptomatic illness using CDC criteria	Time to first case of SARS-CoV-2 RT-PCR- positive symptomatic illness occurring = 28 days post first dose or > 7 days after second dose of study intervention using CDC criteria.	FROM > 28 DAYS POST FIRST DOSE (DAY 1) UP TO DAY 360
Secondary	Time to first COVID-19 related Emergency Department admission	Time to first COVID-19-related Emergency Department admission occurring = 28 days post single dose or = 7 days post second dose of study intervention.	FROM > 28 DAYS POST FIRST DOSE (DAY 1) UP TO DAY 360
Secondary	Time to COVID-19 related death	Time to COVID-19 related death	FROM > 28 DAYS POST FIRST DOSE (DAY 1) UP TO DAY 360
Secondary	Post-treatment GMTs in SARS-CoV-2 S and/or RBD antibodies	Post-treatment GMTs from day of dosing baseline value to 35 days post first dose (14 days post second dose) in SARS-CoV-2 S and/or RBD antibodies	from day of dosing baseline value to 35 days after first dose
Secondary	Post-treatment GMFRs in SARS-CoV-2 S and/or RBD antibodies	Post-treatment GMFRs from day of dosing baseline value to 35 days post first dose (14 days post second dose) in SARS-CoV-2 S and/or RBD antibodies	from day of dosing baseline value to 35 days after first dose
Secondary	Proportion of participants who have a post-treatment seroresponse (= 4-fold rise in titers) in S and/or RBD antigens of GRAd-COV2.	The proportion of participants who have a post-treatment seroresponse (= 4-fold rise in titers from day of dosing baseline value to 35 days post first dose) to the S and/or RBD antigens of GRAd-COV2.	from day 1 to day 36
Secondary	Post-treatment GMTs in SARS-CoV2 S neutralizing antibodies	Post-treatment GMTs from day of dosing baseline value to 35 days post first dose (14 days post second dose) in SARS-CoV-2 neutralizing antibodies.	from day of dosing baseline value to 35 days after first dose
Secondary	Post-treatment GMFRs in SARS-CoV2 S neutralizing antibodies	Post-treatment GMFRs from day of dosing baseline value to 35 days post first dose (14 days post second dose) in SARS-CoV-2 neutralizing antibodies.	from day of dosing baseline value to 35 days after first dose
Secondary	Proportion of participants with post-treatment seroresponse (> 4-fold rise in titers) in SARS-COV2 neutralizing antibodies	Proportion of participants who have a post-treatment seroresponse (= 4-fold rise in titers from day of dosing baseline value to 35 days post first dose) to GRAd-COV2 as measured by SARS-CoV-2 neutralizing antibodies.	from day 1 to day 36