An Interventional, Double-Blinded, 2-Arm Study to Investigate the Efficacy of Orally Administered Nirmatrelvir/Ritonavir Compared With Placebo/Ritonavir in Non-hospitalized Adult Participants Suffering From Post-COVID

KI-PROLIFIC-2023

The purpose of this study is to investigate the efficacy of orally administered nirmatrelvir/ritonavir compared with placebo/ritonavir to improve quality of life in non-hospitalized adult participants suffering from post-acute COVID-19 syndrome.

2023-05-01

2024-01-31

2024-03-31

Recruiting

Early phase I

400

Inclusion Criteria: 1. The subject has given written consent to participate in the study. 2. ≥18 years of age at the time of the Screening Visit. 3. Post-acute COVID-19 syndrome (PACS) according to the WHO definition. 4. EQ-5D-5L VAS\< 50 5. All fertile participants must agree to use a highly effective method of contraception for the duration of the study and 28 days after last intake of the IMP. Exclusion Criteria: General exclusion criteria 1. Other non-related conditions with PACS like symptoms. 2. Renal function eGFR eGFRCysC \< 60 mL/min/1.73 m2. 3. Not able to comply with the study protocol. 4. Previous Paxlovid treatment. 5. Pregnancy or breastfeeding. 6. Drug-drug interaction with ongoing treatment, including concomitant use of any medications or substances that are strong inducers of CYP3A4 within 28 days prior to first dose of nirmatrelvir/ritonavir and during study treatment. 7. Participants who are planning or considering vaccination (including boosters) through Study Day 45. 8. Active COVID-19 infection as verified by SARS CoV-2 positive antigen test. 9. Self-reported medical conditions, including: 1. Type 1 or Type 2 diabetes mellitus. 2. Chronic kidney disease. 3. Neurodevelopmental disorders (e.g., cerebral palsy, Down's syndrome) or other conditions that confer medical complexity (e.g., genetic or metabolic syndromes and severe congenital anomalies). 4. Active cancer other than localized skin cancer, including those requiring treatment including palliative treatment), as long as the treatment is not among the prohibited medications that must be administered/continued during the trial period. 5. Immunosuppressive disease (e.g., bone marrow or organ transplantation or primary immune deficiencies) OR prolonged use of immune-weakening medications: i. Has received corticosteroids equivalent to prednisone ≥20 mg daily for at least 14 consecutive days within 30 days prior to study entry. ii. Has received treatment with biologics (e.g., infliximab, ustekinumab, etc.), immunomodulators (e.g., methotrexate, 6MP, azathioprine, etc.), or cancer chemotherapy within 90 days prior to study entry. iii. HIV infection with CD4+ cell count \<200/mm3. 10. History of hospitalization for the medical treatment of acute COVID-19 11. Current need for hospitalization or anticipated need for hospitalization within 48 hours after randomization in the clinical opinion of the site investigator. 12. Prior/Concomitant Therapy: 1. Current or expected use of any medications or substances that are highly dependent on CYP3A4 for clearance, and for which elevated plasma concentrations may be associated with serious and/or life-threatening events during treatment and for 4 days after the last dose of nirmatrelvir/ritonavir. List of potential interactions provided by Pfizer provided in Appendix A. 2. Has received or is expected to receive monoclonal antibody treatment, antiviral treatment (e.g., molnupiravir), or convalescent COVID-19 plasma. Prior/Concurrent Clinical Study Experience: 13. Is unwilling to abstain from participating in another interventional clinical study with an investigational compound or device, including those for post-COVID-19 therapeutics, through the long-term follow-up visit. 14. Previous administration with any investigational drug or vaccine within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). 15. Known prior participation in this trial or other trial involving nirmatrelvir. Diagnostic Assessments: 16. Known history of any of the following abnormalities in clinical laboratory tests (within past 6 months of the screening visit): * AST or ALT level ≥2.5 X ULN * Total bilirubin ≥2 X ULN (≥3 X ULN for Gilbert's syndrome)

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'This is a phase II, interventional, randomized, parallel group, double-blind, placebo-controlled, single-center study of nirmatrelvir/ritonavir (300/100 mg) or placebo/ritonavir (100mg), administered orally twice daily for 15 days in non-hospitalized patients with post- COVID conditions.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 400, 'type': 'ESTIMATED'}}

2023-06-23