OPtimisation of Antiviral Therapy in Immunocompromised COVID-19 Patients: a Randomized Factorial Controlled Strategy Trial (OPTICOV)
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| ClinicalTrials.gov Identifier: NCT05587894 |
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Recruitment Status :
Recruiting
First Posted : October 20, 2022
Last Update Posted : March 28, 2024
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| COVID-19 Immunodeficiency | Drug: Paxlovid 5 days Drug: Paxlovid 10 days Drug: Veklury | Phase 2 |
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).
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 256 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | OPtimisation of Antiviral Therapy in Immunocompromised COVID-19 Patients: a Randomized Factorial Controlled Strategy Trial: the OPTICOV Study |
| Actual Study Start Date : | April 27, 2023 |
| Estimated Primary Completion Date : | March 2025 |
| Estimated Study Completion Date : | May 2025 |
| Arm | Intervention/treatment |
|---|---|
| Experimental: Nirmatrelvir/r 5 days alone |
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. Other Name: Nirmatrevlir/ritonavir |
| Experimental: Nirmatrelvir/r 10 days alone |
Drug: Paxlovid 10 days
Nirmatrelvir/r 300mg/100 mg bid will be given for 10 days, orally.
Other Name: Nirmatrevlir/ritonavir |
| Experimental: Nirmatrelvir/r 5 days + remdesivir s.d |
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. Other Name: Nirmatrevlir/ritonavir 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.
Other Name: remdesivir |
| Experimental: Nirmatrelvir/r 10 days + remdesivir s.d |
Drug: Paxlovid 10 days
Nirmatrelvir/r 300mg/100 mg bid will be given for 10 days, orally.
Other Name: Nirmatrevlir/ritonavir 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.
Other Name: remdesivir |
- 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. [ Time Frame: Day 10 ]SARS-CoV-2 viral load is measured in nasopharyngeal swabs by real-time RT-PCR
- 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 [ Time Frame: Day5, Day14 and Day21 ]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 [ Time Frame: Assessed for 14 days from the date of randomisation 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 [ Time Frame: Day5, Day10, Day14, Day21 ]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 [ Time Frame: Day5, Day10, Day14 and Day21 ]Emergence of mutations is measured in nasopharyngeal swabs by genotyping techniques
- Time to first negative SARS-CoV-2 RT-PCR (CT<32) until Day90 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Day5, Day10, Day14, Day21 and Day28 ]FLU-PRO-Plus score is measured via an arithmetic formula
- All-cause hospitalization and/or death at Day28 [ Time Frame: Day28 ]Outcome measured during patients medical follow-up
- Hospitalization at Day28 [ Time Frame: Day28 ]Outcome measured during patients medical follow-up
- Death at Day28 [ Time Frame: Day28 ]Outcome measured during patients medical follow-up
- Rate of Post-COVID19 condition at Day90 according to the WHO October 2021 definition [ Time Frame: Day 90 ]
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 [ Time Frame: Day 28 ]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 [ Time Frame: 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 [ Time Frame: Assessed up to Day 10 from randomisation ]Outcome measured during patients medical follow-up
- Percentage of patients with specific retreatment patients (by antiviral antiinflammatory drugs or convalescent plasma through Day90 [ Time Frame: Day90 ]Outcome measured during patients medical follow-up
- To assess the phenotypic resistance (IC50 increase) against treatment for viral strains cultured from nasopharyngeal swabs [ Time Frame: Day5, Day10, Day14, Day21 ]Outcome measured in nasopharyngeal swabs by phenotyping techniques
- Immunosuppressors residual concentrations, if applicable [ Time Frame: as needed ]Outcome measures in participants' blood samples
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 16 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Laboratory confirmed SARS-CoV-2 infection by RT-PCR or positive antigenic test
- 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;
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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
- 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
- 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)
- Body weight < 40 kg
- AST or ALT > 5 times the upper limit
- Cirrhosis Child-Pugh score C
- 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, 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
- 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 with exception of those having received one or two doses of nirmatrevir/r in the 24h preceding the inclusion in the study.
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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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05587894
| Contact: Douae Ammour | +33782960531 | douae.ammour@inserm.fr | |
| Contact: Chiara Fedeli | +41 (0)22 372 9817 | chiara.fedeli@hug.ch |
Show 18 study locations
| Responsible Party: | Alexandra Calmy, HIV/AIDS Unit Director, University Hospital, Geneva |
| ClinicalTrials.gov Identifier: | NCT05587894 |
| Other Study ID Numbers: |
ANRS 0176s OPTICOV CT-2022-501408-81-01 ( Registry Identifier: EMA CTIS ) |
| First Posted: | October 20, 2022 Key Record Dates |
| Last Update Posted: | March 28, 2024 |
| Last Verified: | March 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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COVID-19 Pneumonia, Viral Pneumonia Respiratory Tract Infections Infections Virus Diseases Coronavirus Infections Coronaviridae Infections Nidovirales Infections RNA Virus Infections Lung Diseases Respiratory Tract Diseases Ritonavir Remdesivir |
Nirmatrelvir and ritonavir drug combination HIV Protease Inhibitors Viral Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors Antimetabolites |