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Covid19Phase 2/3COVITARNCT04791423

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

A Phase 2/3 study testing GRAd-COV2 in people with Covid19, run by ReiThera Srl at 26 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Covid19
What is being tested?
GRAd-COV2
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
10,300 participants
Where
26 sitesItaly
Study dates
15 Mar 2021to 13 May 2022
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 16Show fewer
  • 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
  • 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.

Trial locations and contacts

26 sites in 1 country.

26 sites in 1 country

Italy26 sites

  • Azienda Ospedaliera San Giuseppe Moscati

    Avellino, 83100

  • Ospedale Vittorio Emanuele Ii

    Bisceglie, Barletta- Andria-Trani, 76011

  • A.O. Sant'Anna E San Sebastiano Caserta

    Caserta, 81100

  • Asst Di Cremona

    Cremona, 26100

  • Azienda Ospedaliero-Universitaria Di Ferrara

    Ferrara, 44121

  • Ao Ospedali Riuniti - Foggia

    Foggia, 71122

  • E.O. Ospedali Galliera

    Genova, 16128

  • Presidio Ospedaliero Nord-Ospedale Santa Maria Goretti Latina

    Latina, 04100

  • Fondaz.Irccs Ca' Granda - Ospedale Maggiore Policlinico

    Milan, 20122

  • Asst Fatebenefratelli Sacco

    Milan, 20157

  • Ospedale S.Gerardo - Monza

    Monza, 20900

  • Azienda Ospedaliera Dei Colli - P Cotugno

    Naples, 80131

  • Azienda Ospedaliera Universitaria Della Universita' Vanvitelli I Di Napoli

    Naples, 80138

  • Az.Osp.Univ.P.Giaccone

    Palermo, 90127

  • Azienda Ospedaliero-Universitaria Di Parma

    Parma, 43126

  • Policlinico S. Matteo - Pavia

    Pavia, 27100

  • Azienda Usl Di Piacenza

    Piacenza, 29121

  • Azienda Ospedaliero-Universitaria Pisana

    Pisa, 56126

  • Istituto per le Malattie Infettive Lazzaro Spallanzani IRCCS

    Roma, RM, 00149

  • Azienda Ospedaliera Policlinico Umberto I

    Roma, 00161

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

    Roma, 00168

  • Ospedale Amedeo Di Savoia

    Torino, 10149

  • Azienda Sanitaria Universitaria Integrata Di Trieste

    Trieste, 34128

  • Asst Dei Sette Laghi

    Varese, 21100

  • Ospedale Unico Del Vercellese - Ospedale Sant'Andrea

    Vercelli, 13100

  • Centro Ricerche Cliniche Di Verona Srl

    Verona, 37134

Other trials in Italy

About this study

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

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
Being tested
GRAd-COV2, Placebo
Medical subject headings
COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GRAd-COV2Biological

    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

  • PlaceboOther

    Saline solution

Study groups in NCT04791423
Study groupRoleWhat they receive
Single dose of GRAd-COV2Experimental1 single IM dose of GRAd-COV2 2 x 10^11 vp plus 1 dose of saline placebo after 21 days
Receives: Biological: GRAd-COV2
Double dose of GRAd-COV2Experimental2 repeated (21 days apart) IM dose of GRAd-COV2 1 x 10^11
Receives: Biological: GRAd-COV2
PlaceboPlacebo comparatorTwo doses of saline placebo on day 1 and day 22
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

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

  2. 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.

    Measured: 28 DAYS POST EACH DOSE FOR AEs and FROM RANDOMIZATION UP TO DAY 360 FOR SAEs, MAAEs, and AESI

  3. Incidence of local and systemic solicited AEs

    Incidence of local and systemic solicited AEs

    Measured: 7 DAYS POST EACH DOSE OF STUDY INTERVENTION

  4. 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.

    Measured: from day 1 to day 36

  5. 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.

    Measured: from day 1 to day 36

  6. 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.

    Measured: from day 1 to day 36

Secondary outcomes (11)

  1. 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

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

  2. 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.

    Measured: from Day 1 up to day 360

  3. 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.

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

  4. 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.

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

  5. Time to COVID-19 related death

    Time to COVID-19 related death

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

  6. 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

    Measured: from day of dosing baseline value to 35 days after first dose

  7. 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

    Measured: from day of dosing baseline value to 35 days after first dose

  8. 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.

    Measured: from day 1 to day 36

  9. 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.

    Measured: from day of dosing baseline value to 35 days after first dose

  10. 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.

    Measured: from day of dosing baseline value to 35 days after first dose

  11. 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.

    Measured: from day 1 to day 36

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Mar 2021
  2. Study start15 Mar 2021
  3. Primary completion4 Jun 2021
  4. Study completion13 May 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
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.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
10,300 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04791423
Sponsor's protocol ID
RT-CoV-2_01
Acronym
COVITAR
Status last verified
May 2022
First submitted
22 Feb 2021
Last updated
29 Mar 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 37315558

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing GRAd-COV2 in people with Covid19, run by ReiThera Srl at 26 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with symptomatic laboratory confirmed COVID-19 (time frame: FROM > 28 DAYS POST FIRST DOSE (DAY 1) UP TO DAY 360). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04791423, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2023.

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