A Phase 2 Randomized, Double-blind, Placebo-controlled Trial and Open Label Extension to Evaluate the Safety and Efficacy of Deupirfenidone (LYT-100) in Post-acute COVID-19 Respiratory Disease
Overview
- Phase
- Phase 2
- Intervention
- LYT-100
- Conditions
- Covid19
- Sponsor
- PureTech
- Enrollment
- 185
- Locations
- 31
- Primary Endpoint
- Change in distance walked on the six-minute walk test (6MWT)
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief Summary
This study is being conducted in two parts, A and B. Part A is a randomized, double-blind, parallel arm study to evaluate the safety and efficacy of LYT-100 compared to placebo in adults with post-acute COVID-19 respiratory complications. Part B is an Open Label Extension (OLE) study for patients who complete Part A.
Detailed Description
Part A of this study is a randomized, double-blind, parallel arm study being conducted at approximately 35 centers globally to evaluate the safety and efficacy of LYT-100 compared to placebo in 168 adults with post-acute COVID-19 respiratory complications who were treated with mechanical ventilation, extracorporeal membrane oxygenation, non-invasive ventilation (eg CPAP or BiPAP), high-flow nasal oxygen therapy or any other means of oxygen administration in the hospital for at least 1 day and have required only low flow nasal oxygen or no oxygen supplementation for at least 72 hours prior to screening. LYT-100 or placebo will be taken daily for up to 91 days with the primary outcome of change in distance walked on the six-minute walk test performed in line with the American Thoracic Society Respiratory Society Guidelines assessed at Day 91. Secondary endpoints, including pharmacokinetics, inflammatory biomarkers, imaging, and patient-reported outcomes of dyspnea and the 36-Item Short Form Health Survey will also be evaluated. The second part of the study, Part B, is an open-label extension in which eligible patients who completed Part A will be enrolled and treated with open-label LYT-100 for an additional 91 days. The primary endpoint for Part B of the study is to assess the longer-term safety, tolerability, and efficacy of LYT-100 through up to 182 days of treatment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Positive result of a molecular RT-qPCR diagnostic test or SARS-CoV-2 RNA result from a clinical specimen deemed clinically associated with the current episode of illness, warranting hospital admission as per investigator's judgement, or previously hospitalized (central and/or local laboratory COVID-19 test results are accepted from any biological material source)
- •Hospitalization for COVID-19 respiratory disease and treated with supplemental oxygen (including MV, ECMO or any other means of oxygen administration) in hospital for at least 1 day
- •COVID-19 pneumonia findings on imaging (chest X-ray or CT Scan) with a minimum of two lung lobes involvement
- •Able to bear weight and ambulate a minimum of 10 m distance (use of inhaled oxygen permitted)
- •Shortness of breath ≥ grade 3 on mBDS dyspnea scale and not requiring MV, ECMO, NIV, and/or HFNO (nasal O2 is allowed) for at least 72 hours before screening
Exclusion Criteria
- •Pre-existing chronic respiratory condition(s), obstructive or restrictive, for which the patient is actively taking concomitant medication are excluded. Patients with history of Idiopathic Pulmonary Fibrosis (IPF), lung cancer, pulmonary arterial hypertension, other interstitial lung diseases, severe cardiac insufficiency (grade IV) are excluded irrespective of whether they are actively being medicated for those conditions or not.
- •Pre-existing co-morbid conditions preventing outcome assessments, e.g., neurological, medical, orthopedic injury/disability, disease or condition that would prevent ability to transfer and walk for 6 minutes, prior to confirmed COVID-19 diagnosis
- •Unstable angina or myocardial infarction in the last month prior to screening
- •Patients on MV, ECMO, NIV, and/or HFNO within the last 72 hours prior to screening
Arms & Interventions
LYT-100
LYT-100 taken orally twice a day (BID) for 91 days
Intervention: LYT-100
Placebo
Placebo matching LYT-100 taken orally BID for 91 days
Intervention: Placebo
Open Label Extension LYT-100
Open Label Extension: LYT-100 taken orally BID for 91 days The Open Label Extension (Part B) was terminated after results of the Double Blind Portion.
Intervention: LYT-100
Outcomes
Primary Outcomes
Change in distance walked on the six-minute walk test (6MWT)
Time Frame: Baseline to Day 91
The 6MWT is a validated endpoint commonly used in clinical trial research
Secondary Outcomes
- Change in Dyspnoea-12 score(Baseline to Day 91)
- Change in Modified Borg Dyspnoea Scale (mBDS) score(Baseline to Day 91)
- Quality of Life assessment as collected using the SF-36(Baseline to Day 91)
- Change in Saint George Respiratory Questionnaire-I (SGRQ-I) score(Baseline to Day 91)