LYT-100 in Post-acute COVID-19 Respiratory Disease

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Covid19

Intervention / Treatment
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* Drug: LYT-100
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key 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 Key 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LYT-100<br>LYT-100 taken orally BID for 91 days | Drug: LYT-100<br>* oral administration<br>* Other names: Deupirfenidone;|
| Placebo Comparator: Placebo<br>Placebo matching LYT-100 taken orally BID for 91 days | Other: Placebo<br>* oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in distance walked on the six-minute walk test (6MWT) | The 6MWT is a validated endpoint commonly used in clinical trial research | Baseline to Day 91 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Dyspnoea-12 score | Dyspnoea-12 measures breathlessness severity without reference to current activity and was developed for use in interstitial lung disease and COPD current experience (these days.) The tool generates a total score using 12 descriptor items including seven physical and five affective items with response options none (0), mild (1), moderate (2) or severe (3). The total score ranges from 1 to 36 whereby the higher score correlates with greater breathlessness severity. | Baseline to Day 91 | 
| Change in Saint George Respiratory Questionnaire-I (SGRQ-I) score | Saint George Respiratory Questionnaire-I (SGRQ-I) is an idiopathic pulmonary fibrosis disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with interstitial lung disease. There are 34 self-completed items with 3 domain component scores (Symptoms, Activities, and Impacts), with higher scores indicating more limitations. | Baseline to Day 91 | 
| Change in Modified Borg Dyspnoea Scale (mBDS) score | The mBDS is an assessment tool that analyzes breathlessness under exertion. It starts at number 0 where breathing is causing no difficulty at all and progresses through to number 10 where breathing difficulty is maximal. | Baseline to Day 91 | 
| Quality of Life assessment as collected using the SF-36 | The SF-36 (v2) is a self-administered questionnaire containing 36 items that measures functional status, well-being and overall evaluation of health in 8 domains. | Baseline to Day 91 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19 Respiratory Disease, novel coronavirus, respiratory complications, SARS-CoV-2, post acute, lung fibrosis, interstitial lung disease, long COVID, long haul COVID