NCT05668091

A Decentralized, Randomized Phase 2 Efficacy and Safety Study of Nirmatrelvir/Ritonavir in Adults with Long COVID.

An Interventional Decentralized Phase 2, Randomized, Double-Blind, 2-Arm Study to Investigate the Efficacy and Safety of Orally Administered Nirmatrelvir/Ritonavir Compared with Placebo/Ritonavir in Participants with Long COVID

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (actual)
• Sponsor: Harlan M Krumholz · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This decentralized trial is a Phase 2, 1:1 randomized, double-blind, superiority, placebo-controlled study in an anticipated 100 non-hospitalized highly symptomatic adult participants with long COVID. It seeks to determine the efficacy, safety, and tolerability of 15 days of Paxlovid (nirmatrelvir/ritonavir), an anti-viral agent, compared with placebo plus ritonavir. The hypothesis is that viral persistence contributes to long COVID in some patients and nirmatrelvir/ritonavir compared with placebo/ritonavir can improve general health status in participants with long COVID. The study will also seek immune signatures associated with treatment response (overseen by Professor Akiko Iwasaki). The decentralized study does not require site visits, and participants in all 48 states including the District of Columbia, who meet entry criteria can enroll. It is designed to make it convenient to participate. The study drugs will be delivered to the participant's designated address. Long COVID is also known as post-acute sequelae of SARS-CoV-2 (PASC).

Detailed description

This decentralized Phase 2, 1:1 randomized, double-blind, superiority, placebo-controlled trial in non-hospitalized symptomatic adult participants with long COVID will investigate the efficacy, safety, and tolerability of 15 days of treatment with nirmatrelvir/ritonavir compared with placebo/ritonavir. The hypothesis is that 15 days of treatment with nirmatrelvir/ritonavir compared with placebo/ritonavir for the treatment of highly symptomatic, adult participants with long COVID will improve their general health as assessed by the National Institutes of Health (NIH) Patient-Reported Outcomes Measurement Information System (PROMIS)-29 version 2.1 Physical Health Summary Score at Day 28 (2 weeks after the end of the trial drug treatment). This randomized trial is intended to inform future research and will involve an investigation into markers of response. The primary outcome is the PROMIS-29 Physical Health Summary Score. Secondary outcomes will include the PROMIS subscales and items; the Modified General Symptom Questionnaire (Modified GSQ-30) with PROMIS Cognitive Function v.2.0 - Short Form 6a and supplemental symptoms questionnaire and items; the COVID Core Outcome Measure for Recovery; the EuroQol EQ-5D-5L (USA Version); the Functional Assessment of Chronic Illness Therapy (FACIT)-Item GP5; the Patient Global Impression of Severity (PGIS), Patient Global Impression of Change (PGIC), and symptom assessments and healthcare utilization and death. The trial will also employ immunophenotyping to explore the effects of treatment on immune signatures and immune markers of response. In addition, there will be an evaluation of safety endpoints. The trial will randomize 100 participants 18 years and older and able to provide legal consent, with long COVID (history of SARS-CoV-2 infection, symptoms consistent with long COVID beginning after the index infection and continuing more than 12 weeks); with a current fair or worse health status and a good or better health status before the index infection and no known other obvious reason for a depressed health status. Exclusion criteria include HIV infection; pregnancy; breastfeeding; renal impairment (eGFR \<60 mL/min/1.73 m2); hepatic impairment (Child-Pugh Class B or C); history of clinically significant hypersensitivity reactions \[e.g., toxic epidermal necrolysis (TEN) or Stevens-Johnson syndrome\] to the product; known or suspected debilitating chronic conditions or those associated with an impaired immune system that pre-date the long COVID syndrome.

Conditions

• Long COVID

Interventions

Type	Name	Description
DRUG	Nirmatrelvir	Two 150 mg tablets taken by mouth every 12 hours.
DRUG	Ritonavir	One 100 mg capsule taken by mouth every 12 hours.
DRUG	Placebo	Two tablets containing placebo matching nirmatrelvir taken by mouth every 12 hours.

Timeline

• Start date: 2023-04-14
• Primary completion: 2024-04-09
• Completion: 2024-08-21
• First posted: 2022-12-29
• Last updated: 2024-12-02

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study