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

Phase 2

Terminated

• Conditions: Post-acute COVID-19 Respiratory Disease; Covid19
• Interventions: Drug: LYT-100; Other: Placebo

• Registration Number: NCT04652518
• Lead Sponsor: PureTech

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.

Study Timeline

• Study First Submitted: 2020-12-02
• Study First Submitted QC: 2020-12-02
• Study First Posted: 2020-12-03
• Study Start: 2020-12-11
• Primary Completion: 2022-06-28
• Study Completion: 2022-07-18
• Disposition First Submitted: 2023-06-28
• Status Verified: 2023-10
• Last Update Submitted: 2024-02-12
• Disposition First Posted: 2024-02-14
• Last Update Posted: 2024-02-14

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 185

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LYT-100	LYT-100	LYT-100 taken orally twice a day (BID) for 91 days
Open Label Extension LYT-100	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.
Placebo	Placebo	Placebo matching LYT-100 taken orally BID for 91 days

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Change in Dyspnoea-12 score	Baseline to Day 91	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.
Change in Modified Borg Dyspnoea Scale (mBDS) score	Baseline to Day 91	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.
Quality of Life assessment as collected using the SF-36	Baseline to Day 91	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.
Change in Saint George Respiratory Questionnaire-I (SGRQ-I) score	Baseline to Day 91	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.

Trial Locations

Locations (31)

University of Southern California - Keck School of Medicine; 🇺🇸 Los Angeles, California, United States

Center for Advanced Research and Education; 🇺🇸 Gainesville, Georgia, United States

GenHarp Clinical Solutions; 🇺🇸 Evergreen Park, Illinois, United States

Circuit Clinical/Crystal Run Healthcare LLP; 🇺🇸 Middletown, New York, United States

Southeastern Research Center; 🇺🇸 Winston-Salem, North Carolina, United States

North Alabama Medical Center; 🇺🇸 Florence, Alabama, United States

Coastal Pulmonary and Critical Care; 🇺🇸 Saint Petersburg, Florida, United States

Tampa General Hospital; 🇺🇸 Tampa, Florida, United States

University of Pittsburg Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Frostwood Family Medicine; 🇺🇸 Houston, Texas, United States

Clinica Central S.A; 🇦🇷 Villa Regina, Rio Negro, Argentina

Fundacion Estudios Clinicos; 🇦🇷 Rosario, Santa Fe, Argentina

Investigaciones en Patologias Respiratorias; 🇦🇷 San Miguel De Tucumán, Tucuman, Argentina

CETI - Centro de Estudos em Terapias Inovadoras; 🇧🇷 Curitiba, Parana, Brazil

Instituto de Doencas do Torax; 🇧🇷 Rio De Janeiro, Brazil

Hospital de Clinicas de Porto Alegre; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

PMSI Republican Clinical Hospital "T. Mosneaga"; 🇲🇩 Chisinau, Moldova, Republic of

University of the Philippines Manila - Philippine General Hospital (PGH); 🇵🇭 Manila, Philippines

Quirino Memorial Medical Center (QMMC); 🇵🇭 Quezon City, Philippines

Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr. Victor Babes Craiova; 🇷🇴 Craiova, Romania

Spitalul Clinic De Pneumoftiziologie "Leon Daniello" Cluj-Napoca; 🇷🇴 Cluj-Napoca, Romania

Medical Center of Limited Liability Company "Harmoniya krasy"; 🇺🇦 Kiev, Ukraine

St George's University Hospitals NHS Foundation Trust - St George's Hospital; 🇬🇧 London, United Kingdom

Guy's and St Thomas' NHS Foundation Trust - St Thomas' Hospital; 🇬🇧 London, United Kingdom

Vista Health Research; 🇺🇸 Miami, Florida, United States

Affinity Health Corp; 🇺🇸 Nashville, Tennessee, United States

The University of Texas Health Sciences Center at San Antonio; 🇺🇸 San Antonio, Texas, United States

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

National Institute for Infectious Diseases "Prof. Dr. Matei Balş" (Arensia Eploratory Medicine); 🇷🇴 Bucharest, Romania

Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr. Victor Babes - Timisoara; 🇷🇴 Timişoara, Romania

Central Florida Pulmonary Group; 🇺🇸 Orlando, Florida, United States