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

Covid19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04652518
• Other study ID #: LYT-100-2020-02
• Status: Terminated
• Phase: Phase 2
• Start date: December 11, 2020
• Est. completion date: July 18, 2022

Study information

• Verified date: October 2023
• Source: PureTech
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 185
• Est. completion date: July 18, 2022
• Est. primary completion date: June 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Covid19
• Respiration Disorders
• Respiratory Tract Diseases

Intervention

Drug:
• LYT-100
oral administration

Other:
• Placebo
oral administration

Locations

Country	Name	City	State
Argentina	Fundacion Estudios Clinicos	Rosario	Santa Fe
Argentina	Investigaciones en Patologias Respiratorias	San Miguel De Tucumán	Tucuman
Argentina	Clinica Central S.A	Villa Regina	Rio Negro
Brazil	CETI - Centro de Estudos em Terapias Inovadoras	Curitiba	Parana
Brazil	Hospital de Clinicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto de Doencas do Torax	Rio De Janeiro
Moldova, Republic of	PMSI Republican Clinical Hospital "T. Mosneaga"	Chisinau
Philippines	University of the Philippines Manila - Philippine General Hospital (PGH)	Manila
Philippines	Quirino Memorial Medical Center (QMMC)	Quezon City
Romania	National Institute for Infectious Diseases "Prof. Dr. Matei Bals" (Arensia Eploratory Medicine)	Bucharest
Romania	Spitalul Clinic De Pneumoftiziologie "Leon Daniello" Cluj-Napoca	Cluj-Napoca
Romania	Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr. Victor Babes Craiova	Craiova
Romania	Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr. Victor Babes - Timisoara	Timisoara
Ukraine	Medical Center of Limited Liability Company "Harmoniya krasy"	Kiev
United Kingdom	Guy's and St Thomas' NHS Foundation Trust - St Thomas' Hospital	London
United Kingdom	St George's University Hospitals NHS Foundation Trust - St George's Hospital	London
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	GenHarp Clinical Solutions	Evergreen Park	Illinois
United States	North Alabama Medical Center	Florence	Alabama
United States	Center for Advanced Research and Education	Gainesville	Georgia
United States	Frostwood Family Medicine	Houston	Texas
United States	University of Southern California - Keck School of Medicine	Los Angeles	California
United States	Vista Health Research	Miami	Florida
United States	Circuit Clinical/Crystal Run Healthcare LLP	Middletown	New York
United States	Affinity Health Corp	Nashville	Tennessee
United States	Central Florida Pulmonary Group	Orlando	Florida
United States	University of Pittsburg Medical Center	Pittsburgh	Pennsylvania
United States	Coastal Pulmonary and Critical Care	Saint Petersburg	Florida
United States	The University of Texas Health Sciences Center at San Antonio	San Antonio	Texas
United States	Tampa General Hospital	Tampa	Florida
United States	Southeastern Research Center	Winston-Salem	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
PureTech	Clinipace Worldwide, Novotech (Australia) Pty Limited

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Moldova, Republic of,  Philippines,  Romania,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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