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

Primary Purpose

COVID-19, Immunodeficiency

Status
Recruiting
Phase
Phase 2
Locations
Switzerland
Study Type
Interventional
Intervention
Paxlovid 5 days
Paxlovid 10 days
Veklury
Sponsored by
ANRS, Emerging Infectious Diseases
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Laboratory confirmed SARS-CoV-2 infection by RT-PCR
  2. Asymptomatic or mild to moderate COVID-19 (WHO progression scale ≤5)
  3. ≥ 16 years of age;
  4. Body weight > 40 kg

  5. 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) 53

    • Severe immunosuppression (e.g., HIV infection with CD4 + T cell count <200 / 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 prednisolone >20 mg/day > 3 months], monoclonal antibodies, cytostatics, biological products, etc.) in the last 12 months
    • 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
  6. Willing and able to comply with study requirements and restrictions as described in the informed consent form (ICF)
  7. Enrolled in or a beneficiary of a Social Security program (State Medical Aid (AME) is not a Social Security program)
  8. Participant's or its legal representative's signature of the informed consent form

Exclusion Criteria:

  1. SARS-CoV-2 PCR ≥32 CT at screening
  2. Contra-indication to T/C

  3. Contra-indication to nirmatrelvir/r

    • Study SOPs based on recommendations from Liverpool University (https://www.covid19-druginteractions.org/) will be provided to guide investigators

  4. Creatinin clearance <30ml/mn/.73m² (CKD-EPI)
  5. Is taking or is anticipated to require any prohibited therapies.
  6. Participation in another interventional clinical study through Day 28 with an investigational compound or device, including COVID-19 therapeutics.
  7. 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
  8. Previous exposure to T/C in the 6 months prior to randomization, or nirmatrelvir/r or other mAbs in the 28 days preceding randomization
  9. Argument for the presence of a variant resistant against the reference mAbs, or, if variant identification is not available, the prevalence of variants resistant against the reference mAbs at inclusion is >10% in the study site's area
  10. Pregnant or breastfeeding female, unless additional data are available for the use of the study drugs in this population

Sites / Locations

  • University Hospitals of GenevaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Nirmatrelvir/r 5 days alone

Nirmatrelvir/r 10 days alone

Nirmatrelvir/r 5 days + remdesivir s.d

Nirmatrelvir/r 10 days + remdesivir s.d

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
SARS-CoV-2 viral load is measured in nasopharyngeal swabs by real-time RT-PCR
Percentage of patients with detectable SARS-CoV-2 viremia at Day5, Day10 and Day14
SARS-CoV-2 viremia is measured from plasma samples by real-time RT-PCR
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
SARS-CoV-2 viral load is measured in nasopharyngeal swabs and in blood samples by real-time RT-PCR
Number of de novo emergence of mutations on nasopharyngeal RT-PCR at Day5, Day10, Day14 and Day21 comparatively to screening
Emergence of mutations is measured in nasopharyngeal swabs by genotyping techniques
Time to first negative SARS-CoV-2 RT-PCR (CT<32) until Day90
SARS-CoV-2 viral load is measured in nasopharyngeal swabs by real-time RT-PCR
Absence of ability to cultivate virus from viral cultures from nasopharyngeal swabs at Day5, Day10 and Day21
Viral culture is performed from nasopharyngeal swabs samples
Percentage of patients with sustained resolution or abatement of symptoms defined as a FLU-PRO-Plus score ≤1 at Day5, Day10, Day14, Day21 and Day28
FLU-PRO-Plus score is measured via an arithmetic formula
All-cause hospitalization and/or death at Day28
Outcome measured during patients medical follow-up
Hospitalization at Day28
Outcome measured during patients medical follow-up
Death at Day28
Outcome measured during patients medical follow-up
Maximum WHO 11-point Clinical Progression Scale through Day28
Outcome measured during patients medical follow-up
Any worsening of WHO 11-point Clinical Progression Scale through Day28
Outcome measured during patients medical follow-up
Rate of Post-COVID19 condition at Day90 according to the WHO October 2021 definition
Rate of Post-COVID19 condition at Day90 according to the WHO October 2021 definition: o Post COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include fatigue, shortness of breath, cognitive dysfunction but also others and generally have an impact on everyday functioning. Symptoms may be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms may also fluctuate or relapse over time.
Percentage of participants with an adverse event (AE) or serious adverse event (SAE) or AE leading to treatment discontinuation up to Day28
Outcome measured during patients medical follow-up
Adherence to nirmatrelvir/r with patient-reported adherence and nirmatrelvir/r residual plasma dosage at Day5 and Day10
Outcome measured by patient-reported adherence and drug residual dosage using dried spot (DBS)
Number of DDIs who led to dosage adjustment of other patient's drugs
Outcome measured during patients medical follow-up
Percentage of patients with specific retreatment patients (by antiviral antiinflammatory drugs or convalescent plasma through Day90
Outcome measured during patients medical follow-up

Full Information

First Posted
October 17, 2022
Last Updated
July 27, 2023
Sponsor
ANRS, Emerging Infectious Diseases
Collaborators
University Hospital, Geneva
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1. Study Identification

Unique Protocol Identification Number
NCT05587894
Brief Title
OPtimisation of Antiviral Therapy in Immunocompromised COVID-19 Patients: a Randomized Factorial Controlled Strategy Trial
Acronym
OPTICOV
Official Title
OPtimisation of Antiviral Therapy in Immunocompromised COVID-19 Patients: a Randomized Factorial Controlled Strategy Trial: the OPTICOV Study
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 27, 2023 (Actual)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
January 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
ANRS, Emerging Infectious Diseases
Collaborators
University Hospital, Geneva

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19, Immunodeficiency

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
256 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Nirmatrelvir/r 5 days alone
Arm Type
Experimental
Arm Title
Nirmatrelvir/r 10 days alone
Arm Type
Experimental
Arm Title
Nirmatrelvir/r 5 days + remdesivir s.d
Arm Type
Experimental
Arm Title
Nirmatrelvir/r 10 days + remdesivir s.d
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Paxlovid 5 days
Other Intervention Name(s)
Nirmatrevlir/ritonavir
Intervention Description
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
Intervention Name(s)
Paxlovid 10 days
Other Intervention Name(s)
Nirmatrevlir/ritonavir
Intervention Description
Nirmatrelvir/r 300mg/100 mg bid will be given for 10 days, orally.
Intervention Type
Drug
Intervention Name(s)
Veklury
Other Intervention Name(s)
remdesivir
Intervention Description
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.
Primary Outcome Measure Information:
Title
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.
Description
SARS-CoV-2 viral load is measured in nasopharyngeal swabs by real-time RT-PCR
Time Frame
Day 10
Secondary Outcome Measure Information:
Title
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
Description
SARS-CoV-2 viral load is measured in nasopharyngeal swabs by real-time RT-PCR
Time Frame
Day5, Day14 and Day21
Title
Percentage of patients with detectable SARS-CoV-2 viremia at Day5, Day10 and Day14
Description
SARS-CoV-2 viremia is measured from plasma samples by real-time RT-PCR
Time Frame
Assessed for 14 days from the date of randomisation at Day5, Day10 and Day14
Title
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
Description
SARS-CoV-2 viral load is measured in nasopharyngeal swabs and in blood samples by real-time RT-PCR
Time Frame
Day5, Day10, Day14, Day21
Title
Number of de novo emergence of mutations on nasopharyngeal RT-PCR at Day5, Day10, Day14 and Day21 comparatively to screening
Description
Emergence of mutations is measured in nasopharyngeal swabs by genotyping techniques
Time Frame
Day5, Day10, Day14 and Day21
Title
Time to first negative SARS-CoV-2 RT-PCR (CT<32) until Day90
Description
SARS-CoV-2 viral load is measured in nasopharyngeal swabs by real-time RT-PCR
Time Frame
Day90
Title
Absence of ability to cultivate virus from viral cultures from nasopharyngeal swabs at Day5, Day10 and Day21
Description
Viral culture is performed from nasopharyngeal swabs samples
Time Frame
Day5, Day10 and Day21
Title
Percentage of patients with sustained resolution or abatement of symptoms defined as a FLU-PRO-Plus score ≤1 at Day5, Day10, Day14, Day21 and Day28
Description
FLU-PRO-Plus score is measured via an arithmetic formula
Time Frame
Day5, Day10, Day14, Day21 and Day28
Title
All-cause hospitalization and/or death at Day28
Description
Outcome measured during patients medical follow-up
Time Frame
Day28
Title
Hospitalization at Day28
Description
Outcome measured during patients medical follow-up
Time Frame
Day28
Title
Death at Day28
Description
Outcome measured during patients medical follow-up
Time Frame
Day28
Title
Maximum WHO 11-point Clinical Progression Scale through Day28
Description
Outcome measured during patients medical follow-up
Time Frame
Day28
Title
Any worsening of WHO 11-point Clinical Progression Scale through Day28
Description
Outcome measured during patients medical follow-up
Time Frame
Day 28
Title
Rate of Post-COVID19 condition at Day90 according to the WHO October 2021 definition
Description
Rate of Post-COVID19 condition at Day90 according to the WHO October 2021 definition: o Post COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include fatigue, shortness of breath, cognitive dysfunction but also others and generally have an impact on everyday functioning. Symptoms may be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms may also fluctuate or relapse over time.
Time Frame
Day 90
Title
Percentage of participants with an adverse event (AE) or serious adverse event (SAE) or AE leading to treatment discontinuation up to Day28
Description
Outcome measured during patients medical follow-up
Time Frame
Day 28
Title
Adherence to nirmatrelvir/r with patient-reported adherence and nirmatrelvir/r residual plasma dosage at Day5 and Day10
Description
Outcome measured by patient-reported adherence and drug residual dosage using dried spot (DBS)
Time Frame
Day5 and Day10
Title
Number of DDIs who led to dosage adjustment of other patient's drugs
Description
Outcome measured during patients medical follow-up
Time Frame
Assessed up to Day 10 from randomisation
Title
Percentage of patients with specific retreatment patients (by antiviral antiinflammatory drugs or convalescent plasma through Day90
Description
Outcome measured during patients medical follow-up
Time Frame
Day90

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Laboratory confirmed SARS-CoV-2 infection by RT-PCR Asymptomatic or mild to moderate COVID-19 (WHO progression scale ≤5) ≥ 16 years of age; Body weight > 40 kg 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 <200 / 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, etc.) in the last 12 months 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) Participant's or its legal representative's signature of the informed consent form Exclusion Criteria: SARS-CoV-2 PCR ≥30 CT at screening Hypersensitivity to study drugs (active substance(s) or excipients) Creatinine clearance <30ml/mn/.73m² (CKD-EPI) AST or ALT > 5 times the upper limit Is taking or is anticipated to require any prohibited therapies* Participation in another interventional clinical study through Day 28 with an investigational compound or device, including COVID-19 therapeutics 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 Having received antiviral treatments against SARS-CoV-2 in the 14 days before the inclusion 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Raphaelle Tardieu
Phone
+33782960531
Email
raphaelle.tardieu@anrs.fr
Facility Information:
Facility Name
University Hospitals of Geneva
City
Geneva
ZIP/Postal Code
1205
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexandra Calmy, Prof. MD
Phone
+41 22 372 98 12
Email
alexandra.calmy@hcuge.ch

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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