Optimizing antiviral treatment for immunocompromised people with COVID-19

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

This trial will test whether adding remdesivir to Paxlovid or extending Paxlovid from 5 to 10 days helps immunocompromised people with asymptomatic or mild-to-moderate COVID-19.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 256 (estimated)
• Ages: 16 Years and up
• Sex: All
• Sponsor: University Hospital, Geneva (Academic / other)
• Drugs / interventions: sunitinib, imatinib, cyclophosphamide, prednisone
• Locations: 4 sites (Basel, Basel and 3 other locations)
• Trial ID: NCT07406217 on ClinicalTrials.gov

What this trial studies

This randomized, controlled, factorial Phase 2 trial assigns immunocompromised participants with asymptomatic or mild-to-moderate COVID-19 to receive nirmatrelvir/ritonavir (Paxlovid) alone or combined with remdesivir and independently to 5 versus 10 days of nirmatrelvir/ritonavir. The primary outcome is viral efficacy measured by SARS-CoV-2 RT-PCR positivity (Ct < 32) on nasopharyngeal swab at day 10. Up to 256 patients will be enrolled across sites in Switzerland with parallel recruitment in France, Italy, and Norway, and an optional exploratory non-randomized cohort (up to 97 participants) is available in Switzerland. Safety, viral kinetics, and tolerability will be monitored throughout follow-up.

Who should consider this trial

Good fit: People aged 16 or older who are immunocompromised with laboratory-confirmed asymptomatic or mild-to-moderate SARS-CoV-2 infection and who have no contraindication to the study drugs are eligible.

Not a fit: Patients with more severe COVID-19 (WHO progression scale ≥5), those with contraindications to remdesivir or nirmatrelvir/ritonavir, or those who are not immunocompromised are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the approach could shorten viral shedding and reduce the risk of prolonged infection or clinical progression in immunocompromised patients.

How similar studies have performed: Antiviral monotherapies such as nirmatrelvir/ritonavir and remdesivir have shown benefit in some groups, but combining these agents or extending Paxlovid duration specifically in immunocompromised patients remains largely untested.

Eligibility criteria

Inclusion Criteria:

1. Laboratory confirmed SARS-CoV-2 infection by real time RT-PCR or positive antigenic test (commercialized assay)
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 Federal Office of Public Health (FOPH) list (criteria 5: diseases/treatments leading to immune suppression) or other immunosuppression criteria such as:

   * Severe immunosuppression (e.g., human immunodeficiency virus (HIV) infection with CD4 + T cell count \<350 / μl)
   * Neutropenia (\<1000 neutrophils / μl) ≥1 week
   * Lymphocytopenia (\<200 lymphocytes/μl)
   * On dialysis treatment
   * 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 (Aspartate transaminase) and/or alanine transaminase (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 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

Where this trial is running

Basel, Basel and 3 other locations

• Basel University Hospital — Basel, Basel, Switzerland (Recruiting)
• Hôpitaux Universitaires de Genève — Geneva, Canton of Geneva, Switzerland (Recruiting)
• Chuv — Lausanne, Canton of Vaud, Switzerland (Recruiting)
• University Hospital Zurich — Zurich, Canton of Zurich, Switzerland (Recruiting)

Study contacts

• Principal investigator: Alexandra Calmy, MD PhD — Hopitaux Universitaires de Genève
• Study coordinator: Alexandra Calmy, MD PhD

Conditions COVID-19; Immunodeficiency; Immunodepression; SARS-CoV-2; Paxlovid; Veklury; Viral load