Optimizing antiviral treatment for immunocompromised people with COVID-19

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• 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
• Email: alexandra.calmy@hug.ch
• Phone: +41 22 372 98 12

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.