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

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

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.

Study Overview

• Status: Terminated
• Conditions: Covid19; Post-acute COVID-19 Respiratory Disease
• Intervention / Treatment: Drug: LYT-100; Other: Placebo

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 Type: Interventional
• Enrollment (Actual): 185
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Rio Negro
    • Villa Regina, Rio Negro, Argentina, 8336
      • Clinica Central S.A
  • Santa Fe
    • Rosario, Santa Fe, Argentina, 2000
      • Fundacion Estudios Clinicos
  • Tucuman
    • San Miguel De Tucumán, Tucuman, Argentina, 4000
      • Investigaciones en Patologias Respiratorias
• Brazil
  • Rio De Janeiro, Brazil, 21941-913
    • Instituto de Doencas do Torax
  • Parana
    • Curitiba, Parana, Brazil, 80030-110
      • Ceti - Centro de Estudos Em Terapias Inovadoras
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
      • Hospital De Clinicas De Porto Alegre
• Moldova, Republic of
  • Chisinau, Moldova, Republic of, 2025
    • PMSI Republican Clinical Hospital "T. Mosneaga"
• Philippines
  • Manila, Philippines, 1000
    • University of the Philippines Manila - Philippine General Hospital (PGH)
  • Quezon City, Philippines, 1109
    • Quirino Memorial Medical Center (QMMC)
• Romania
  • Bucharest, Romania
    • National Institute for Infectious Diseases "Prof. Dr. Matei Balş" (Arensia Eploratory Medicine)
  • Cluj-Napoca, Romania, 400332
    • Spitalul Clinic De Pneumoftiziologie "Leon Daniello" Cluj-Napoca
  • Craiova, Romania, 200515
    • Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr. Victor Babes Craiova
  • Timişoara, Romania, 300310
    • Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr. Victor Babes - Timisoara
• Ukraine
  • Kiev, Ukraine, 01135
    • Medical Center of Limited Liability Company "Harmoniya Krasy"
• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Guy's and St Thomas' NHS Foundation Trust - St Thomas' Hospital
  • London, United Kingdom, SW17 0QT
    • St George's University Hospitals NHS Foundation Trust - St George's Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
    • Florence, Alabama, United States, 35630
      • North Alabama Medical Center
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California - Keck School of Medicine
  • Florida
    • Miami, Florida, United States, 33176
      • Vista Health Research
    • Orlando, Florida, United States, 32803
      • Central Florida Pulmonary Group
    • Saint Petersburg, Florida, United States, 33704
      • Coastal Pulmonary and Critical Care
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Center for Advanced Research and Education
  • Illinois
    • Evergreen Park, Illinois, United States, 60805
      • GenHarp Clinical Solutions
  • New York
    • Middletown, New York, United States, 10941
      • Circuit Clinical/Crystal Run Healthcare LLP
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Southeastern Research Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburg Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Affinity Health Corp
  • Texas
    • Houston, Texas, United States, 77024
      • Frostwood Family Medicine
    • San Antonio, Texas, United States, 78229
      • The University of Texas Health Sciences Center at San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo matching LYT-100 taken orally BID for 91 days	Other: Placebo; oral administration
Experimental: LYT-100; LYT-100 taken orally twice a day (BID) for 91 days	Drug: LYT-100; oral administration; Other Names: Deupirfenidone
Other: 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.	Drug: LYT-100; oral administration; Other Names: Deupirfenidone

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: PureTech
• Collaborators: Novotech (Australia) Pty Limited; Clinipace Worldwide
• Investigators: Principal Investigator: Toby Maher, MD, Keck School of Medicine, University of Southern California

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2020
• Primary Completion (Actual): June 28, 2022
• Study Completion (Actual): July 18, 2022

Study Registration Dates

• First Submitted: December 2, 2020
• First Submitted That Met QC Criteria: December 2, 2020
• First Posted (Actual): December 3, 2020

Study Record Updates

• Last Update Posted (Actual): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: SARS-CoV-2; interstitial lung disease; novel coronavirus; respiratory complications; long COVID; long haul COVID; lung fibrosis; COVID-19 Respiratory Disease; post acute; Post-acute COVID-19 Respiratory Disease
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Respiration Disorders; Respiratory Tract Diseases; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Pirfenidone
• Other Study ID Numbers: LYT-100-2020-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No