Clinical trial NCT04791423: Study of GRAd-COV2 for the Prevention of COVID-19 in Adults
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Covid19
Lead sponsor: ReiThera Srl
Sponsor class: INDUSTRY
Collaborators: name: Istituto Nazionale per le Malattie Infettive "Lazzaro Spallanzani" IRCCS
First posted: 2021-03-10
Enrollment: 10300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In the phase II part approximately 900 participants will be randomized in a 1:1:1 ratio to receive 1 single IM dose of GRAd-COV2 2x10\^11 vp plus 1 dose of placebo after 21 days (n= approximately 300 subject) or 2 repeated (21 days apart) IM dose of GRAd-COV2 1x10\^11 (n = approximately 300 subjects) or two doses of placebo (n = approximately 300 subjects) on day 1 and day 22.

Once the phase III expansion is granted, according to the epidemic evolution,the availability on the market of alternative vaccine(s) and the characteristics of vaccination campaign, the phase III study design will be adapted following these 3 potential scenarios: 1) a superiority trial vs placebo on overall population; 2) a superiority trial vs placebo on an subset of population (low risk subjects for infection outcome) or 3) a non-inferiority trial vs the available alternative vaccine on a surrogate endpoint (correlates of protection), if available.
Primary purpose: PREVENTION

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with symptomatic laboratory confirmed COVID-19
timeFrame: FROM > 28 DAYS POST FIRST DOSE (DAY 1) UP TO DAY 360
measure: Incidence of AEs, SAEs, MAAEs, and AESI
timeFrame: 28 DAYS POST EACH DOSE FOR AEs and FROM RANDOMIZATION UP TO DAY 360 FOR SAEs, MAAEs, and AESI
measure: Incidence of local and systemic solicited AEs
timeFrame: 7 DAYS POST EACH DOSE OF STUDY INTERVENTION
measure: Post-treatment GMTs in SARS-CoV2 S and/or RBD antibodies
timeFrame: from day 1 to day 36
measure: Post-treatment GMFRs in SARS-CoV2 S and/or RBD antibodies
timeFrame: from day 1 to day 36
measure: Proportion of participants with post-treatment seroresponse (> 4-fold rise in titers) to the S and/or RBD antigens of GRAd-COV2
timeFrame: from day 1 to day 36
Secondary outcomes:
measure: Time to first SARS-CoV2 RT-PCR positive severe or critical symptomatic illness
timeFrame: FROM > 28 DAYS POST FIRST DOSE (DAY 1) UP TO DAY 360
measure: Proportion of participants who have a post-treatment response for SARS-COV2 Nucleocapside antibodies
timeFrame: from Day 1 up to day 360
measure: Time to first case of SARS-COV2 RT-PCR positive symptomatic illness using CDC criteria
timeFrame: FROM > 28 DAYS POST FIRST DOSE (DAY 1) UP TO DAY 360
measure: Time to first COVID-19 related Emergency Department admission
timeFrame: FROM > 28 DAYS POST FIRST DOSE (DAY 1) UP TO DAY 360
measure: Time to COVID-19 related death
timeFrame: FROM > 28 DAYS POST FIRST DOSE (DAY 1) UP TO DAY 360
measure: Post-treatment GMTs in SARS-CoV-2 S and/or RBD antibodies
timeFrame: from day of dosing baseline value to 35 days after first dose
measure: Post-treatment GMFRs in SARS-CoV-2 S and/or RBD antibodies
timeFrame: from day of dosing baseline value to 35 days after first dose
measure: Proportion of participants who have a post-treatment seroresponse (≥ 4-fold rise in titers) in S and/or RBD antigens of GRAd-COV2.
timeFrame: from day 1 to day 36
measure: Post-treatment GMTs in SARS-CoV2 S neutralizing antibodies
timeFrame: from day of dosing baseline value to 35 days after first dose
measure: Post-treatment GMFRs in SARS-CoV2 S neutralizing antibodies
timeFrame: from day of dosing baseline value to 35 days after first dose
measure: Proportion of participants with post-treatment seroresponse (> 4-fold rise in titers) in SARS-COV2 neutralizing antibodies
timeFrame: from day 1 to day 36
Other outcomes:
Locations:
city: Bisceglie
country: Italy
facility: Ospedale Vittorio Emanuele Ii
state: Barletta- Andria-Trani
city: Roma
country: Italy
facility: Istituto per le Malattie Infettive Lazzaro Spallanzani IRCCS
state: RM
city: Avellino
country: Italy
facility: Azienda Ospedaliera San Giuseppe Moscati
city: Caserta
country: Italy
facility: A.O. Sant'Anna E San Sebastiano Caserta
city: Cremona
country: Italy
facility: Asst Di Cremona
city: Ferrara
country: Italy
facility: Azienda Ospedaliero-Universitaria Di Ferrara
city: Foggia
country: Italy
facility: Ao Ospedali Riuniti - Foggia
city: Genova
country: Italy
facility: E.O. Ospedali Galliera
city: Latina
country: Italy
facility: Presidio Ospedaliero Nord-Ospedale Santa Maria Goretti Latina
city: Milano
country: Italy
facility: Fondaz.Irccs Ca' Granda - Ospedale Maggiore Policlinico
city: Milano
country: Italy
facility: Asst Fatebenefratelli Sacco
city: Monza
country: Italy
facility: Ospedale S.Gerardo - Monza
city: Napoli
country: Italy
facility: Azienda Ospedaliera Dei Colli - P Cotugno
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Della Universita' Vanvitelli I Di Napoli
city: Palermo
country: Italy
facility: Az.Osp.Univ.P.Giaccone
city: Parma
country: Italy
facility: Azienda Ospedaliero-Universitaria Di Parma
city: Pavia
country: Italy
facility: Policlinico S. Matteo - Pavia
city: Piacenza
country: Italy
facility: Azienda Usl Di Piacenza
city: Pisa
country: Italy
facility: Azienda Ospedaliero-Universitaria Pisana
city: Roma
country: Italy
facility: Azienda Ospedaliera Policlinico Umberto I
city: Roma
country: Italy
facility: Policlinico A. Gemelli E C.I.C.- Policlinico Universitario A. Gemelli
city: Torino
country: Italy
facility: Ospedale Amedeo Di Savoia
city: Trieste
country: Italy
facility: Azienda Sanitaria Universitaria Integrata Di Trieste
city: Varese
country: Italy
facility: Asst Dei Sette Laghi
city: Vercelli
country: Italy
facility: Ospedale Unico Del Vercellese - Ospedale Sant'Andrea
city: Verona
country: Italy
facility: Centro Ricerche Cliniche Di Verona Srl
Study officials:
affiliation: Istituto per le Malattie Infettive Lazzaro Spallanzani IRCCS
name: Simone Lanini, Consultant
role: PRINCIPAL_INVESTIGATOR
References: