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

NCT04791423 | Completed Phase 2 DMC

• 1 other identifier: RT-CoV-2_01
• Study Type: interventional
• Target: 10,300
• Locations: 1 country
• Sites: 26

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.

Conditions

Covid19

Outcome Measures

Primary Outcomes (6)

• 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

• Incidence of AEs, SAEs, MAAEs, and AESI

  1. Incidence of AEs for 28 days post each dose of study intervention. 2. 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

• Incidence of local and systemic solicited AEs

  Incidence of local and systemic solicited AEs

  7 DAYS POST EACH DOSE OF STUDY INTERVENTION

• 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

• 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

• 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 Outcomes (11)

• Time to first SARS-CoV2 RT-PCR positive severe or critical symptomatic illness

  FROM > 28 DAYS POST FIRST DOSE (DAY 1) UP TO DAY 360

• Proportion of participants who have a post-treatment response for SARS-COV2 Nucleocapside antibodies

  from Day 1 up to day 360

• Time to first case of SARS-COV2 RT-PCR positive symptomatic illness using CDC criteria

  FROM > 28 DAYS POST FIRST DOSE (DAY 1) UP TO DAY 360

• Time to first COVID-19 related Emergency Department admission

  FROM > 28 DAYS POST FIRST DOSE (DAY 1) UP TO DAY 360

• Time to COVID-19 related death

  FROM > 28 DAYS POST FIRST DOSE (DAY 1) UP TO DAY 360

Study Arms (3)

Single dose of GRAd-COV2

EXPERIMENTAL

1 single IM dose of GRAd-COV2 2 x 10\^11 vp plus 1 dose of saline placebo after 21 days

Biological: GRAd-COV2

Double dose of GRAd-COV2

EXPERIMENTAL

2 repeated (21 days apart) IM dose of GRAd-COV2 1 x 10\^11

Biological: GRAd-COV2

Placebo

PLACEBO COMPARATOR

Two doses of saline placebo on day 1 and day 22

Other: Placebo

Interventions

GRAd-COV2 BIOLOGICAL

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

Double dose of GRAd-COV2; Single dose of GRAd-COV2

Placebo OTHER

Saline solution

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult female and male, ≥ 18 years of age at the time of consent
• 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
• Able to understand and comply with study requirements/procedures based on the assessment of the investigator
• Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
• 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.
• Capable of giving signed informed consent.

You may not qualify if:

• History of allergy to any component of the vaccine
• History of Guillain-Barré syndrome or any other demyelinating condition
• Significant infection or other acute illness, including fever \> 37.3 °C on the day prior to or day of randomization
• History of laboratory-confirmed SARS-CoV-2 infection
• Any confirmed or suspected immunosuppressive or immunodeficient state, including asplenia (only for phase II)
• Recurrent severe infections and use of immunosuppressant medication within the past 6 months
• 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)
• 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
• 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)
• 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
• Receipt of, or planned receipt of investigational or licensed products indicated for the treatment or prevention of SARS-CoV-2 or COVID-19
• Receipt of any vaccine (licensed or investigational) other than licensed influenza vaccines within 30 days prior to and after administration of study intervention
• 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
• Involvement in the planning and/or conduct of this study (applies to both Sponsor staff and/or staff at the study site)
• For women only - currently pregnant (confirmed with positive pregnancy test) or breast-feeding

Sponsors & Collaborators

• ReiThera Srl: lead
• Istituto Nazionale per le Malattie Infettive "Lazzaro Spallanzani" IRCCS: collaborator

Study Sites (26)

Ospedale Vittorio Emanuele Ii

Bisceglie, Barletta- Andria-Trani, 76011, Italy

Location

Istituto per le Malattie Infettive Lazzaro Spallanzani IRCCS

Roma, RM, 00149, Italy

Location

Azienda Ospedaliera San Giuseppe Moscati

Avellino, 83100, Italy

Location

A.O. Sant'Anna E San Sebastiano Caserta

Caserta, 81100, Italy

Location

Asst Di Cremona

Cremona, 26100, Italy

Location

Azienda Ospedaliero-Universitaria Di Ferrara

Ferrara, 44121, Italy

Location

Ao Ospedali Riuniti - Foggia

Foggia, 71122, Italy

Location

E.O. Ospedali Galliera

Genova, 16128, Italy

Location

Presidio Ospedaliero Nord-Ospedale Santa Maria Goretti Latina

Latina, 04100, Italy

Location

Fondaz.Irccs Ca' Granda - Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Asst Fatebenefratelli Sacco

Milan, 20157, Italy

Location

Ospedale S.Gerardo - Monza

Monza, 20900, Italy

Location

Azienda Ospedaliera Dei Colli - P Cotugno

Napoli, 80131, Italy

Location

Azienda Ospedaliera Universitaria Della Universita' Vanvitelli I Di Napoli

Napoli, 80138, Italy

Location

Az.Osp.Univ.P.Giaccone

Palermo, 90127, Italy

Location

Azienda Ospedaliero-Universitaria Di Parma

Parma, 43126, Italy

Location

Policlinico S. Matteo - Pavia

Pavia, 27100, Italy

Location

Azienda Usl Di Piacenza

Piacenza, 29121, Italy

Location

Azienda Ospedaliero-Universitaria Pisana

Pisa, 56126, Italy

Location

Azienda Ospedaliera Policlinico Umberto I

Roma, 00161, Italy

Location

Policlinico A. Gemelli E C.I.C.- Policlinico Universitario A. Gemelli

Roma, 00168, Italy

Location

Ospedale Amedeo Di Savoia

Torino, 10149, Italy

Location

Azienda Sanitaria Universitaria Integrata Di Trieste

Trieste, 34128, Italy

Location

Asst Dei Sette Laghi

Varese, 21100, Italy

Location

Ospedale Unico Del Vercellese - Ospedale Sant'Andrea

Vercelli, 13100, Italy

Location

Centro Ricerche Cliniche Di Verona Srl

Verona, 37134, Italy

Location

Related Publications (1)

• Capone S, Fusco FM, Milleri S, Borre S, Carbonara S, Lo Caputo S, Leone S, Gori G, Maggi P, Cascio A, Lichtner M, Cauda R, Dal Zoppo S, Cossu MV, Gori A, Roda S, Confalonieri P, Bonora S, Missale G, Codeluppi M, Mezzaroma I, Capici S, Pontali E, Libanore M, Diani A, Lanini S, Battella S, Contino AM, Piano Mortari E, Genova F, Parente G, Dragonetti R, Colloca S, Visani L, Iannacone C, Carsetti R, Folgori A, Camerini R; COVITAR study group. GRAd-COV2 vaccine provides potent and durable humoral and cellular immunity to SARS-CoV-2 in randomized placebo-controlled phase 2 trial. Cell Rep Med. 2023 Jun 20;4(6):101084. doi: 10.1016/j.xcrm.2023.101084. Epub 2023 May 29.

  PMID: 37315558 DERIVED

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Simone Lanini, Consultant

  Istituto per le Malattie Infettive Lazzaro Spallanzani IRCCS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The phase II part of the study is a parallel-group preventive study with 3 arms that is participant and investigator blinded (observer blinded). The blinding of the phase III will depend on the scenario that will be implemented.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 22, 2021
• First Posted: March 10, 2021
• Study Start: March 15, 2021
• Primary Completion: June 4, 2021
• Study Completion: May 13, 2022
• Last Updated: March 29, 2023

Record last verified: 2022-05

Locations

IT (26)