Trial of Treatments for COVID-19 in Hospitalized Adults

• Status: Recruiting
• Trial end date: 2023-03-01
• Target enrollment: 0
• Participant gender: All

Summary

DisCoVeRy is a randomized controlled trial among adults (≥18-year-old) hospitalized for COVID-19. This study is an adaptive, randomized, open or blinded, depending on the drug to be evaluated, clinical trial to evaluate the safety and efficacy of possible therapeutic agents in hospitalized adult patients diagnosed with COVID-19. The study is a multi-centre/country trial that will be conducted in various sites in Europe with Inserm as sponsor. The study will compare different investigational therapeutic agents to a control group managed with the SoC including corticosteroids and anticoagulants. There will be interim monitoring to allow early stopping for safety and to introduce new therapies as they become available. If one therapy proves to be superior to others in the trial, this treatment may become part of the SoC for comparison(s) with new experimental treatment(s).

In previous versions of the DisCoVeRy protocol, remdesivir, lopinavir/ritonavir with or without interferon ß-1a and hydroxychloroquine were evaluated as potential treatments for COVID-19. These treatments have been discontinued based on analyses review by both DSMC/DSMB, the Solidarity Executive Group and the DisCoVeRy steering committee.

This version of the protocol, therefore, describes a randomized blinded placebo-controlled trial among adults (≥18-year-old) hospitalized for COVID-19 that randomly allocates them (1:1 ratio) between 2 arms: SoC + placebo versus SoC + AZD7442.

Randomization will be stratified by region (according to the administrative definition in each country), antigenic status (positive or negative) obtained from the result of a rapid antigen test on nasopharyngeal swab performed at enrolment and vaccination initiation (yes or no).

The primary analyses will be conducted on patients with antigen-positive results. A positive antigenic test is evidence of high viral shedding consistent with a recently started or uncontrolled infection. Overall, the number of antigen-negative patients will be at most 30% of all included subjects. The number of patients with vaccination (partly or fully) will be limited to 20% of all participants, split evenly between antigen positive and antigen negative patients (i.e. vaccinated patients can make up at most 20% of antigene positive patients and 20% of antigene negative patients). Sensitivity analyses will be performed in all patients, stratified by antigenic status and vaccination initiation.

A global independent data and safety monitoring board (DSMB) monitors interim data to make recommendations about early study closure or changes to conduct, including adding or removing treatment arms. However, the current version of the protocol does not allow for efficacy or futility analysis, and the ability to add trial arms will be limited by the study being blinded and placebo-controlled during the investigation of AZD7442.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Treatments: Hydroxychloroquine; Interferon beta-1a; Interferon-beta; Interferons; Lopinavir; Remdesivir; Ritonavir

Criteria

Inclusion Criteria:

1. Adult ≥18 years of age at the time of enrolment

2. Hospitalized patients with any of the following criteria:

1. the presence of pulmonary rales/crackles on clinical exam OR

2. SpO2 ≤ 94% on room air OR

3. requirement of supplementary oxygen including high flow oxygen devices or non-invasive ventilation

3. A time between onset of symptoms and randomization of less than 11 days

4. A positive SARS-CoV-2 PCR performed on a NP swab within the 5 days preceding randomization

5. The result of a rapid antigen test performed on a NP swab within the 6 hours preceding randomization

6. Contraceptive use by men or women.

1. Male participants: Contraception for male participants is required; to avoid the transfer of any fluids, all male participants must use a condom from Day 1 and agree to continue for 90 days following administration of IMP.

2. Female participants: Women of child-bearing potential must agree to use contraception for 365 days following administration of IMP

Exclusion Criteria:

1. Refusal to participate expressed by patient or legally authorized representative

2. Need for invasive mechanical ventilation and/or ECMO at the time of enrolment

3. Spontaneous blood ALT/AST levels > 5 times the upper limit of normal

4. Glomerular filtration rate (GFR) < 15 mL/min or requiring maintenance dialysis

5. Pregnancy or breast-feeding

6. Anticipated transfer to another hospital, which is not a study site within 72 hours following randomization

7. Known history of allergy or reaction to any component of the study drug formulation.

8. Previous hypersensitivity, infusion-related reaction, or severe adverse reaction following administration of monoclonal or polyclonal antibodies.

9. Any prior receipt of investigational or licensed other mAb/biologic indicated for the prevention of SARS-CoV-2 infection or COVID-19, and for those not vaccinated, expected receipt of vaccine in the 30 days following hospital discharge, according to current recommendation in each country.

10. Any medical condition which, in the judgment of the investigator, could interfere with the interpretation of the trial results or that preludes to protocol adherence.