OPtimisation of Antiviral Therapy in Immunocompromised COVID-19 Patients (SWISS OPTICOV)

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

The overall purpose of the trial is to evaluate the efficacy and safety of possible combination antiviral therapy direct antiviral agents (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 Coronavirus Disease 2019 (COVID-19).

Study Overview

• Status: Recruiting
• Conditions: COVID-19; Immunodeficiency
• Intervention / Treatment: Drug: Paxlovid 10 days; Drug: Paxlovid 5 days

Detailed Description

This is a randomized, controlled, factorial, superiority trial to evaluate the viral efficacy of direct antiviral agent nirmatrelvir/r + direct antiviral agent 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 antiviral agents (nirmatrelvir/r + remdesivir and/or (ii) an increase in nirmatrelvir/ r duration from 5 to 10 days improves viral efficacy by decreasing the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV- 2) positivity rate by real time polymerase chain reaction (RT-PCR) (cycle threshold CT<32) in nasopharyngeal swabs at day 10 (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 recruited in Switzerland and in France, Italy and Norway (through the parallel protocol ANRS0176s OPTICOV).

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, active only in Switzerland).

• Study Type: Interventional
• Enrollment (Estimated): 256
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Alexandra Calmy, MD PhD; Phone Number: +41 22 372 98 12; Email: alexandra.calmy@hug.ch
• Study Contact Backup: Name: Chiara Fedeli, PhD; Phone Number: +41 (0)22 372 9817; Email: chiara.fedeli@hug.ch

Study Locations

• Switzerland
  • Basel
    • Basel, Basel, Switzerland, 4031
      • Recruiting
      • Basel University Hospital
      • Contact: Nina Khanna; Phone Number: +41 61 328 73 25; Email: nina.khanna@usb.ch
  • Canton of Geneva
    • Geneva, Canton of Geneva, Switzerland, 1205
      • Recruiting
      • Hopitaux Universitaires de Geneve
      • Contact: Alexandra Calmy; Phone Number: +41 22 372 98 12; Email: alexandra.calmy@hug.ch
  • Canton of Vaud
    • Lausanne, Canton of Vaud, Switzerland, 10-549
      • Recruiting
      • CHUV
      • Contact: Oriol Manuel; Phone Number: +41 21 314 3020; Email: oriol.manuel@chuv.ch
  • Canton of Zurich
    • Zurich, Canton of Zurich, Switzerland, 8091
      • Recruiting
      • University Hospital Zurich
      • Contact: Nicolas Muller; Phone Number: +41 1 255 37 12; Email: nicolas.mueller@usz.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Nirmatrelvir/ritonavir (nirmatrelvir/r) 5 days alone; Nirmatrelvir/r 300mg/100 mg bis in die (twice a day, bid) will be given for 5 days, orally. Nirmatrelvir/r is a combination of two molecules: nirmatrelvir which is a protease inhibitor (against 3CL) and ritonavir which has a booster role. Nirmatrelvir/r (marketed by Pfizer under the brand name Paxlovid®) is indicated for the treatment of COVID-19 in adults who do not require supplemental oxygen and who are at increased risk for progressing to severe COVID-19. Paxlovid® for 5 days is the standard of care.	Drug: Paxlovid 5 days; Nirmatrelvir/r 300mg/100 mg bid will be given for 5 days, orally. Nirmatrelvir/r is a combination of two molecules: nirmatrelvir which is a protease inhibitor (against 3CL) and ritonavir which has a booster role. Nirmatrelvir/r (marketed by Pfizer under the brand name Paxlovid®) is indicated for the treatment of COVID-19 in adults who do not require supplemental oxygen and who are at increased risk for progressing to severe COVID-19.
Experimental: Nirmatrelvir/ritonavir (nirmatrelvir/r) 10 days alone; Intervention Nirmatrelvir/r 300mg/100 mg bid will be given for 10 days, orally.	Drug: Paxlovid 10 days; Nirmatrelvir/r 300mg/100 mg bid will be given for 10 days, orally.
Experimental: Nirmatrelvir/ritonavir (nirmatrelvir/r) 5 days + remdesivir single dose; Nirmatrelvir/r 300mg/100 mg bid will be given for 5 days, orally. Nirmatrelvir/r is a combination of two molecules: nirmatrelvir which is a protease inhibitor (against 3CL) and ritonavir which has a booster role. Nirmatrelvir/r (marketed by Pfizer under the brand name Paxlovid®) is indicated for the treatment of COVID-19 in adults who do not require supplemental oxygen and who are at increased risk for progressing to severe COVID-19. Remdesivir "flash", 200mg, intravenous. Remdesivir (marketed by Gilead under de brand name Veklury®) is indicated in patients with pneumonia requiring supplemental oxygen (inpatients), as well as in outpatients who are at increased risk of progressing to severe COVID-19. The mode of action characterize remdesivir as a direct-acting antiviral compound.	Drug: Paxlovid 5 days; Nirmatrelvir/r 300mg/100 mg bid will be given for 5 days, orally. Nirmatrelvir/r is a combination of two molecules: nirmatrelvir which is a protease inhibitor (against 3CL) and ritonavir which has a booster role. Nirmatrelvir/r (marketed by Pfizer under the brand name Paxlovid®) is indicated for the treatment of COVID-19 in adults who do not require supplemental oxygen and who are at increased risk for progressing to severe COVID-19.
Experimental: Nirmatrelvir/ritonavir (nirmatrelvir/r) 10 days + remdesivir single dose; Nirmatrelvir/r 300mg/100 mg bid will be given for 10 days, orally. Remdesivir "flash", 200mg, intravenous. Remdesivir (marketed by Gilead under de brand name Veklury®) is indicated in patients with pneumonia requiring supplemental oxygen (inpatients), as well as in outpatients who are at increased risk of progressing to severe COVID-19. The mode of action characterize remdesivir as a direct-acting antiviral compound.	Drug: Paxlovid 10 days; Nirmatrelvir/r 300mg/100 mg bid will be given for 10 days, orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virological	Percentage of patients with SARS-CoV-2 viral load <32 cycle threshold (CT) by real-time RT-PCR in nasopharyngeal swabs at D10 after treatment initiation.	Day 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virological	Percentage of patients with SARS-CoV-2 viral load <32 CT by real-time RT-PCR in nasopharyngeal swabs at D5, D14 and D21 after treatment initiation	Day 5, Day 14, Day 21
Virological	Percentage of patients with detectable SARS-CoV-2 viremia at D5, D10 and D14	Day 5, Day 10, Day 14
Virological	Decrease of SARS-CoV-2 viral load measured by copies/ml by nasopharyngeal swab at D5, D10, D14, D21 and at D5, D10 and D14 in blood samples comparatively to screening	Day 5, Day 10, Day 14, Day 21
Virological	Number of de novo mutations after sequencing on nasopharyngeal swabs at D5, D10, D14 and D21 comparatively to screening	Day 5, Day 10, Day 14, Day 21
Virological	Time to first negative SARS-CoV-2 RT-PCR (CT<32) until D90	Day 90
Virological	Absence of ability to cultivate virus from viral cultures from nasopharyngeal swabs at D5, D10, D14 and D21	Day 5, Day 10, Day 14, Day 21
Clinical	All-cause hospitalization and/or death at D28	Day 28
Clinical	Hospitalization at D28	Day 28
Clinical	Death at D28	Day 28
Clinical	Percentage of participants with an adverse event (AE) or serious adverse event (SAE) or AE leading to treatment discontinuation up to D90	Day 90
Clinical	Adherence to nirmatrelvir/r with patient-reported adherence and nirmatrelvir/r residual plasma dosage at D5 and D10, if applicable	Day 5, Day 10
Clinical	Number of drud-drug interactions who led to dosage adjustment of other patient's drugs	Day 10
Clinical	Immunosuppressors residual concentrations, if applicable	Day 10
Clinical	Percentage of patients with specific retreatment (by antiviral, anti-inflammatory drug or convalescent plasma) through D90	Day 90
Virological	To assess the phenotypic resistance (Half maximal inhibitory concentration (IC50) increase) against treatment for viral strains cultured from nasopharyngeal swabs at D5, D10, D14 and D21 comparatively to screening	Day 5, Day 10, Day 14, Day 21
Clinical	Percentage of patients with sustained resolution or abatement of symptoms defined as a inFLUenza Patient-Reported Outcome Plus (FLU-PRO-Plus) score ≤1 at D5, D10, D14, D21 and D28	Day 5, Day 10, Day14, Day 21, Day 28
Clinical	inFLUenza Patient-Reported Outcome Plus (FLU-PRO-Plus) scale at D5, D10, D14, D21, D28 and D90. Scores range from 0 (symptom free) to 4 (very severe symptoms).	Day 5, Day 10, Day 14, Day 21, Day 28, Day 90
Clinical	Rate of Post-COVID19 condition at D90 according to the World Health Organisation (WHO) October 2021 definition	Day 90
Clinical	Number of drug-drug interactions (DDIs) which led to dosage adjustment of other patient's drugs	Day 10

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment discontinuation outcome because of AE or SAE	Percentage of participants with an adverse event (AE) or serious adverse event (SAE) or AE leading to treatment discontinuation up to D90	Day 90

Collaborators and Investigators

• Sponsor: Calmy Alexandra
• Collaborators: ANRS, Emerging Infectious Diseases
• Investigators: Principal Investigator: Alexandra Calmy, MD PhD, Hopitaux Universitaires de Geneve; Principal Investigator: Nina Khanna, MD PhD, Basel University Hospital; Principal Investigator: Nicolas Muller, MD PhD, University of Zurich; Principal Investigator: Oriol Manuel, MD PhD, University Hospital CHUV

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2023
• Primary Completion (Estimated): April 10, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: February 5, 2026
• First Submitted That Met QC Criteria: February 5, 2026
• First Posted (Actual): February 12, 2026

Study Record Updates

• Last Update Posted (Actual): February 18, 2026
• Last Update Submitted That Met QC Criteria: February 13, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; Paxlovid; Viral load; Immunodepression; Veklury
• Additional Relevant MeSH Terms: Immune System Diseases; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Immunologic Deficiency Syndromes; nirmatrelvir and ritonavir drug combination
• Other Study ID Numbers: 2022-01720; 62987 (Other Identifier: Human research Switzerland (HumRes)); FNS 320003B_212963 (Other Identifier: Swiss National Fundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual Participant Data are described in the study protocol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No