OPtimisation of Antiviral Therapy in Immunocompromised COVID-19 Patients: a Randomized Factorial Controlled Strategy Trial (OPTICOV)

ANRS, Emerging Infectious Diseases

Status and phase: Enrolling; Phase 2

Conditions: COVID-19; Immunodeficiency

Treatments: Drug: Veklury; Drug: Paxlovid 10 days; Drug: Paxlovid 5 days

Study type: Interventional

Funder types: Other

Identifiers

NCT05587894

CT-2022-501408-81-01 (Registry Identifier)

ANRS 0176s OPTICOV

Details and patient eligibility

About

The overall purpose of the trial is to evaluate the efficacy and safety of possible combination antiviral therapy DAA (remdesivir + nirmatrelvir/r)∞ versus the reference monotherapy (nirmatrelvir/r alone) and to assess the efficacy and safety of increasing the nirmatrelvir/r course from 5- to 10 days in immunocompromised patients diagnosed with asymptomatic or mild to moderate COVID-19.

Full description

This is a randomized, controlled, factorial, superiority trial to evaluate the viral efficacy of DAA (nirmatrelvir/r) + DAA (remdesivir)∞ versus nirmatrelvir/r alone and of 5 days versus 10 days of nirmatrelvir/r in immunocompromised patients diagnosed with asymptomatic or mild to moderate COVID-19.

The primary objective is to assess whether (i) a combination antiviral therapy of two DAA (nirmatrelvir/r + remdesivir)∞ And/or (ii) an increase in nirmatrelvir/r duration from 5 to 10 days improves viral efficacy by decreasing the SARS-CoV-2 positivity rate by real time RT-PCR (CT<32) in nasopharyngeal swabs at D10.

Patients will be eligible if they are immunocompromised, have confirmed asymptomatic SARS-CoV-2 infection or mild to moderate COVID-19, regardless of symptoms onset, provided that they have no contra-indication to any of the study drugs.

A total of 256 patients will be included in France and Switzerland.

Participants not eligible for randomisation or who refuse to participate to the trial for any reason will be proposed to be included in an exploratory non comparative cohort (maximum 97 participants).

Enrollment: 256 estimated patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Laboratory confirmed SARS-CoV-2 infection by RT-PCR or positive antigenic test

2. Asymptomatic or mild to moderate COVID-19 (WHO progression scale <5). Patients receiving oxygen therapy for reasons other than a pulmonary COVID-19 are eligible)

3. ≥ 16 years of age;

4. Immunocompromised as defined by ≥ 1 risk factors for severe COVID-19 as assessed by the FOPH list (criteria 5: diseases/treatments leading to immune suppression)

   • Severe immunosuppression (e.g., HIV infection with CD4 + T cell count <350 / µl)
   • Neutropenia (<1000 neutrophils / µl) ≥1 week
   • Lymphocytopenia (<200 lymphocytes/µl)
   • Hereditary immunodeficiencies
   • Intake of drugs which suppress the immune system (e.g. glucocorticoids for a long time [an equivalent dose of prednisone >20 mg/day > 3 months], monoclonal antibodies, cytostatics, biological products, everolimus, mTOR inhibitors etc.) in the last 12 months
   • Active cancer under cytostatics or targeted therapy known to be immunosuppressive (e.g., platinum salts, cyclophosphamide, anthracyclines, taxanes, 5-fluorouracil, gemcitabine, purine inhibitors, proteasome inhibitors) or associated with hematologic toxicity (neutropenia, lymphopenia), for example sunitinib, imatinib, regorafenib
   • Aggressive lymphomas (all types)
   • Acute lymphatic leukemia
   • Acute myeloid leukemia
   • Acute promyelocytic leukemia
   • T prolymphocytic leukemia
   • Primary central nervous system lymphoma
   • Stem cell transplantation
   • Light chain amyloidosis
   • Chronic lymphoid leukemia
   • Multiple myeloma
   • Sickle cell disease
   • Bone marrow transplant
   • Organ transplant
   • Being on the waiting list for an organ transplant

5. Willing and able to comply with study requirements and restrictions as described in the informed consent form (ICF)

6. Enrolled in or a beneficiary of a Social Security program (State Medical Aid (AME) is not a Social Security program) or holders of health insurance

7. Participant's or its legal representative's signature of the informed consent form

Exclusion criteria

1. SARS-CoV-2 PCR ≥30 CT at screening

2. Hypersensitivity to study drugs (active substance(s) or excipients)

3. Body weight < 40 kg

4. AST or ALT > 5 times the upper limit

5. Cirrhosis Child-Pugh score C

6. Is taking or is anticipated to require any prohibited therapies*

7. Participation in another interventional clinical study through Day 28 with an investigational compound or device, including COVID-19 therapeutics, where the study intervention is performed in the 28 days preceding the inclusion and the 10 days after the inclusion. Investigators of the different clinical studies should agree on participant's inclusion

8. Presence of any condition for which, in the opinion of the investigator, participation would not be in participant's best interest or that could prevent, limit, or confound the protocol-specified assessments

9. Having received antiviral treatments against SARS-CoV-2 in the 14 days before the inclusion with exception of those having received one or two doses of nirmatrevir/r in the 24h preceding the inclusion in the study.

10. Pregnant or breastfeeding female

    • Study SOPs based on recommendations from the Liverpool COVID-19 interactions, French Society for Pharmacology and Therapeutics and French Speaking Transplantation society will be provided to guide investigators

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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256 participants in 4 patient groups

Nirmatrelvir/r 5 days alone

Experimental group

Treatment:

Drug: Paxlovid 5 days

Nirmatrelvir/r 10 days alone

Experimental group

Treatment:

Drug: Paxlovid 10 days

Nirmatrelvir/r 5 days + remdesivir s.d

Experimental group

Treatment:

Drug: Paxlovid 5 days

Drug: Veklury

Nirmatrelvir/r 10 days + remdesivir s.d

Experimental group

Treatment:

Drug: Paxlovid 10 days

Drug: Veklury