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

NCT ID: NCT05587894

Last Updated: 2024-03-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

256 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-04-27

Study Completion Date

2025-05-31

Brief Summary

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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.

Detailed Description

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This is a randomized, controlled, factorial, superiority trial to evaluate the viral efficacy of DAA (nirmatrelvir/r) + DAA (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 DAA (nirmatrelvir/r + remdesivir)∞ And/or (ii) an increase in nirmatrelvir/r duration from 5 to 10 days improves viral efficacy by decreasing the SARS-CoV-2 positivity rate by real time RT-PCR (CT\<32) in nasopharyngeal swabs at 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 included in France and Switzerland.

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).

Conditions

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COVID-19 Immunodeficiency

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Nirmatrelvir/r 5 days alone

Group Type EXPERIMENTAL

Paxlovid 5 days

Intervention Type DRUG

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.

Nirmatrelvir/r 10 days alone

Group Type EXPERIMENTAL

Paxlovid 10 days

Intervention Type DRUG

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

Nirmatrelvir/r 5 days + remdesivir s.d

Group Type EXPERIMENTAL

Paxlovid 5 days

Intervention Type DRUG

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.

Veklury

Intervention Type DRUG

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.

Nirmatrelvir/r 10 days + remdesivir s.d

Group Type EXPERIMENTAL

Paxlovid 10 days

Intervention Type DRUG

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

Veklury

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Paxlovid 10 days

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

Intervention Type DRUG

Veklury

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.

Intervention Type DRUG

Other Intervention Names

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Nirmatrevlir/ritonavir Nirmatrevlir/ritonavir remdesivir

Eligibility Criteria

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Inclusion Criteria

1. Laboratory confirmed SARS-CoV-2 infection by RT-PCR or positive antigenic test
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 FOPH list (criteria 5: diseases/treatments leading to immune suppression)

* Severe immunosuppression (e.g., HIV infection with CD4 + T cell count \<350 / 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 \[an equivalent dose of prednisone \>20 mg/day \> 3 months\], 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 or 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 through Day 28 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 SOPs based on recommendations from the Liverpool COVID-19 interactions, French Society for Pharmacology and Therapeutics and French Speaking Transplantation society will be provided to guide investigators
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Geneva

OTHER

Sponsor Role collaborator

ANRS, Emerging Infectious Diseases

OTHER_GOV

Sponsor Role lead

Responsible Party

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Alexandra Calmy

HIV/AIDS Unit Director

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Saint-André Hospital

Bordeaux, , France

Site Status RECRUITING

Pellegrin Hospital

Bordeaux, , France

Site Status RECRUITING

Francois Mitterrand Hospital

Dijon, , France

Site Status RECRUITING

Croix Rousse Hospital

Lyon, , France

Site Status RECRUITING

La Colombière Hospital

Montpellier, , France

Site Status RECRUITING

Hotel Dieu Hospital

Nantes, , France

Site Status RECRUITING

Laribosière Hospital

Paris, , France

Site Status RECRUITING

Saint Antoine Hospital

Paris, , France

Site Status RECRUITING

Pitié-Salpêtrière Hospital

Paris, , France

Site Status RECRUITING

Saint Louis Hospital

Paris, , France

Site Status RECRUITING

Bichat Claude-Bernard Hospital

Paris, , France

Site Status RECRUITING

Robert Debré Hospital

Reims, , France

Site Status RECRUITING

Purpan Hospital

Toulouse, , France

Site Status RECRUITING

Tourcoing Hospital

Tourcoing, , France

Site Status RECRUITING

Basel University Hospital

Basel, , Switzerland

Site Status RECRUITING

University Hospitals of Geneva

Geneva, , Switzerland

Site Status RECRUITING

University Hospital CHUV

Lausanne, , Switzerland

Site Status NOT_YET_RECRUITING

University Hospital Zurich

Zurich, , Switzerland

Site Status RECRUITING

Countries

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France Switzerland

Central Contacts

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Douae Ammour

Role: CONTACT

+33782960531

Chiara Fedeli

Role: CONTACT

+41 (0)22 372 9817

Facility Contacts

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Fabrice Bonnet, Prof. MD

Role: primary

+33 5 56 79 58 23

Didier Neau, Prof. MD

Role: primary

+33 5 67 95 523

Lionel Piroth, Prof. MD

Role: primary

+33 3 30 29 33 05

Florence Ader, Prof. MD

Role: primary

+33 4 72 07 11 07

Alain Makinson, Prof. MD

Role: primary

+33 4 67 33 95 10

Francois Raffi, Prof. MD

Role: primary

+33 2 40 08 33 51

Sandra Devantine, Dr

Role: primary

+33 6 18 74 00 01

Karine Lacombe, Prof. MD

Role: primary

+33 1 49 28 24 38

Valérie Pourcher, Prof MD

Role: primary

+33 1 42 16 41 84

Jean-Michel Molina, Prof. MD

Role: primary

+33 1 42 49 90 66

Jade Ghosn, Prof. MD

Role: primary

+33 14 02 58 860

Maxime Hentzien, Prof. MD

Role: primary

+33 6 07 85 01 77

Guillaume Martin Blondel, Prof. MD

Role: primary

+33 5 62 74 61 46

Olivier Robineau

Role: primary

+33 3 20 69 46 17

Nina Khanna, Prof. MD

Role: primary

+41 61 328 73 25

Alexandra Calmy, Prof. MD

Role: primary

+41 22 372 98 12

Oriol Manuel, Prof MD

Role: primary

+41 21 314 3020

Nicolas Muller, Prof. MD

Role: primary

+41 1 255 37 12

Other Identifiers

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CT-2022-501408-81-01

Identifier Type: REGISTRY

Identifier Source: secondary_id

ANRS 0176s OPTICOV

Identifier Type: -

Identifier Source: org_study_id

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