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

• Status: Not yet recruiting
• Trial end date: 2025-01-01
• Target enrollment: 0
• Participant gender: All

Summary

The overall purpose of the trial is to evaluate the efficacy and safety of possible combination antiviral therapy (mAbs (T/C)∞ + 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.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: ANRS, Emerging Infectious Diseases
• Collaborator: University Hospital, Geneva
• Treatments: Ritonavir

Criteria

Inclusion Criteria:

1. Laboratory confirmed SARS-CoV-2 infection by RT-PCR

2. Asymptomatic or mild to moderate COVID-19 (WHO progression scale ≤5)

3. ≥ 16 years of age;

4. Body weight > 40 kg

5. 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) 53

• Severe immunosuppression (e.g., HIV infection with CD4 + T cell count <200 / 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 prednisolone >20 mg/day > 3 months], monoclonal antibodies, cytostatics, biological products, etc.) in the last 12 months

• 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

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

7. Enrolled in or a beneficiary of a Social Security program (State Medical Aid (AME) is not a Social Security program)

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

Exclusion Criteria:

1. SARS-CoV-2 PCR ≥32 CT at screening

2. Contra-indication to T/C

3. Contra-indication to nirmatrelvir/r

• Study SOPs based on recommendations from Liverpool University (https://www.covid19-druginteractions.org/) will be provided to guide investigators

4. Creatinin clearance <30ml/mn/.73m² (CKD-EPI)

5. Is taking or is anticipated to require any prohibited therapies.

6. Participation in another interventional clinical study through Day 28 with an investigational compound or device, including COVID-19 therapeutics.

7. 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

8. Previous exposure to T/C in the 6 months prior to randomization, or nirmatrelvir/r or other mAbs in the 28 days preceding randomization

9. Argument for the presence of a variant resistant against the reference mAbs, or, if variant identification is not available, the prevalence of variants resistant against the reference mAbs at inclusion is >10% in the study site's area

10. Pregnant or breastfeeding female, unless additional data are available for the use of the study drugs in this population