NCT05587894

Brief Summary

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.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
256

participants targeted

Target at P75+ for phase_2 covid19

Timeline
14mo left

Started Apr 2023

Longer than P75 for phase_2 covid19

Geographic Reach
3 countries

18 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress73%
Apr 2023Jun 2027

First Submitted

Initial submission to the registry

October 17, 2022

Completed
3 days until next milestone

First Posted

Study publicly available on registry

October 20, 2022

Completed
6 months until next milestone

Study Start

First participant enrolled

April 27, 2023

Completed
3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2026

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2027

Last Updated

February 23, 2026

Status Verified

February 1, 2026

Enrollment Period

3.2 years

First QC Date

October 17, 2022

Last Update Submit

February 19, 2026

Conditions

Outcome Measures

Primary Outcomes (1)

  • Percentage of patients with SARS-CoV-2 viral load (threshold cicle (Ct) <32) by real-time RT-PCR in nasopharyngeal swabs at Day 10 after treatment initiation.

    SARS-CoV-2 viral load is measured in nasopharyngeal swabs by real-time RT-PCR

    Day 10

Secondary Outcomes (17)

  • Percentage of patients with SARS-CoV-2 viral load (threshold cicle <32 CT) by real-time RT-PCR in nasopharyngeal swabs at Day5, Day14 and Day21 after treatment initiation

    Day5, Day14 and Day21

  • Percentage of patients with detectable SARS-CoV-2 viremia at Day5, Day10 and Day14

    Assessed for 14 days from the date of randomisation at Day5, Day10 and Day14

  • Decrease of SARS-CoV-2 viral load measured by copies/ml by nasopharyngeal swab at Day5, Day10, Day14, Day21 and in blood samples at Day5, Day10 and Day14 comparatively to screening

    Day5, Day10, Day14, Day21

  • Number of de novo emergence of mutations on nasopharyngeal RT-PCR at Day5, Day10, Day14 and Day21 comparatively to screening

    Day5, Day10, Day14 and Day21

  • Time to first negative SARS-CoV-2 RT-PCR (CT<32) until Day90

    Day90

  • +12 more secondary outcomes

Study Arms (4)

Nirmatrelvir/r 5 days alone

EXPERIMENTAL
Drug: Paxlovid 5 days

Nirmatrelvir/r 10 days alone

EXPERIMENTAL
Drug: Paxlovid 10 days

Nirmatrelvir/r 5 days + remdesivir s.d

EXPERIMENTAL
Drug: Paxlovid 5 daysDrug: Veklury

Nirmatrelvir/r 10 days + remdesivir s.d

EXPERIMENTAL
Drug: Paxlovid 10 daysDrug: Veklury

Interventions

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.

Also known as: Nirmatrevlir/ritonavir
Nirmatrelvir/r 5 days + remdesivir s.dNirmatrelvir/r 5 days alone

Nirmatrelvir/r 300mg/100 mg bid will be given for 10 days, orally.

Also known as: Nirmatrevlir/ritonavir
Nirmatrelvir/r 10 days + remdesivir s.dNirmatrelvir/r 10 days alone

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.

Also known as: remdesivir
Nirmatrelvir/r 10 days + remdesivir s.dNirmatrelvir/r 5 days + remdesivir s.d

Eligibility Criteria

Age16 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Laboratory confirmed SARS-CoV-2 infection by RT-PCR or positive antigenic test (commercialized assay)
  • 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).
  • ≥ 16 years of age (for patients recruited in Italy and in Norway, ≥ 18 years of age);
  • 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) or other immunosuppression criteria such as Severe immunosuppression (e.g., 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
  • Willing and able to comply with study requirements and restrictions as described in the informed consent form (ICF)
  • 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 (LAF for participants recruited in Norway).
  • Participant's or its legal representative's signature of the informed consent form

You may not qualify if:

  • SARS-CoV-2 PCR ≥30 CT at screening
  • Hypersensitivity to study drugs (active substance(s) or excipients)
  • Body weight \< 40 kg
  • AST and/or ALT \> 5 times the upper limit
  • Cirrhosis Child-Pugh score C
  • Is taking or is anticipated to require any prohibited therapies\*.
  • 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
  • Pregnant or breastfeeding female
  • Study SOPs based on recommendations from the Liverpool COVID-19 interactions, French Society for Pharmacology and Therapeutics (https://sfpt-fr.org/recommandations-et-publications) and French Speaking Transplantation Society will be provided to guide investigators.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (18)

Saint-André Hospital

Bordeaux, Bordeaux, 33075, France

RECRUITING

Pellegrin Hospital

Bordeaux, Bordeaux, 33076, France

RECRUITING

Francois Mitterrand Hospital

Dijon, Dijon, 21079, France

RECRUITING

Croix Rousse Hospital

Lyon, Lyon, 69317, France

RECRUITING

La Colombière Hospital

Montpellier, Montpellier, 34295, France

RECRUITING

Hotel Dieu Hospital

Nantes, Nantes, 44093, France

RECRUITING

Laribosière Hospital

Paris, Paris, 75010, France

RECRUITING

Saint Antoine Hospital

Paris, Paris, 75012, France

RECRUITING

Pitié-Salpêtrière Hospital

Paris, Paris, 75013, France

RECRUITING

Saint Louis Hospital

Paris, Paris, 75474, France

RECRUITING

Bichat Claude-Bernard Hospital

Paris, Paris, 75877, France

RECRUITING

Robert Debré Hospital

Reims, Reims, 51092, France

RECRUITING

Purpan Hospital

Toulouse, Toulouse, 31059, France

RECRUITING

Tourcoing Hospital

Tourcoing, Tourcoing, 59208, France

RECRUITING

Division of Infectious Diseases, Verona University Hospital

Verona, Italy

RECRUITING

Drammen Hospital, Vestre Viken Hospital

Drammen, 3004, Norway

RECRUITING

Oslo University Hospital and University of Oslo

Oslo, 0372, Norway

RECRUITING

Vestfold Hospital Trust

Tønsberg, 3103, Norway

RECRUITING

MeSH Terms

Conditions

COVID-19Immunologic Deficiency Syndromes

Interventions

nirmatrelvir and ritonavir drug combinationRitonavirremdesivir

Condition Hierarchy (Ancestors)

Pneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsVirus DiseasesCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung DiseasesRespiratory Tract DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

ThiazolesSulfur CompoundsOrganic ChemicalsAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER GOV
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 17, 2022

First Posted

October 20, 2022

Study Start

April 27, 2023

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

June 30, 2027

Last Updated

February 23, 2026

Record last verified: 2026-02

Locations