Clinical trial NCT04652518: LYT-100 in Post-acute COVID-19 Respiratory Disease
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Covid19
Post-acute COVID-19 Respiratory Disease
Keywords: COVID-19 Respiratory Disease
novel coronavirus
respiratory complications
SARS-CoV-2
post acute
lung fibrosis
interstitial lung disease
long COVID
long haul COVID
Post-acute COVID-19 Respiratory Disease
Lead sponsor: PureTech
Sponsor class: INDUSTRY
Collaborators: name: Clinipace Worldwide
name: Novotech (Australia) Pty Limited
First posted: 2020-12-03
Enrollment: 185
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in distance walked on the six-minute walk test (6MWT)
timeFrame: Baseline to Day 91
Secondary outcomes:
measure: Change in Dyspnoea-12 score
timeFrame: Baseline to Day 91
measure: Change in Saint George Respiratory Questionnaire-I (SGRQ-I) score
timeFrame: Baseline to Day 91
measure: Change in Modified Borg Dyspnoea Scale (mBDS) score
timeFrame: Baseline to Day 91
measure: Quality of Life assessment as collected using the SF-36
timeFrame: Baseline to Day 91
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Florence
country: United States
facility: North Alabama Medical Center
state: Alabama
city: Los Angeles
country: United States
facility: University of Southern California - Keck School of Medicine
state: California
city: Miami
country: United States
facility: Vista Health Research
state: Florida
city: Orlando
country: United States
facility: Central Florida Pulmonary Group
state: Florida
city: Saint Petersburg
country: United States
facility: Coastal Pulmonary and Critical Care
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Gainesville
country: United States
facility: Center for Advanced Research and Education
state: Georgia
city: Evergreen Park
country: United States
facility: GenHarp Clinical Solutions
state: Illinois
city: Middletown
country: United States
facility: Circuit Clinical/Crystal Run Healthcare LLP
state: New York
city: Winston-Salem
country: United States
facility: Southeastern Research Center
state: North Carolina
city: Pittsburgh
country: United States
facility: University of Pittsburg Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Affinity Health Corp
state: Tennessee
city: Houston
country: United States
facility: Frostwood Family Medicine
state: Texas
city: San Antonio
country: United States
facility: The University of Texas Health Sciences Center at San Antonio
state: Texas
city: Villa Regina
country: Argentina
facility: Clinica Central S.A
state: Rio Negro
city: Rosario
country: Argentina
facility: Fundacion Estudios Clinicos
state: Santa Fe
city: San Miguel De Tucumán
country: Argentina
facility: Investigaciones en Patologias Respiratorias
state: Tucuman
city: Curitiba
country: Brazil
facility: CETI - Centro de Estudos em Terapias Inovadoras
state: Parana
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: Rio Grande Do Sul
city: Rio De Janeiro
country: Brazil
facility: Instituto de Doencas do Torax
city: Chisinau
country: Moldova, Republic of
facility: PMSI Republican Clinical Hospital "T. Mosneaga"
city: Manila
country: Philippines
facility: University of the Philippines Manila - Philippine General Hospital (PGH)
city: Quezon City
country: Philippines
facility: Quirino Memorial Medical Center (QMMC)
city: Bucharest
country: Romania
facility: National Institute for Infectious Diseases "Prof. Dr. Matei Balş" (Arensia Eploratory Medicine)
city: Cluj-Napoca
country: Romania
facility: Spitalul Clinic De Pneumoftiziologie "Leon Daniello" Cluj-Napoca
city: Craiova
country: Romania
facility: Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr. Victor Babes Craiova
city: Timişoara
country: Romania
facility: Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Dr. Victor Babes - Timisoara
city: Kiev
country: Ukraine
facility: Medical Center of Limited Liability Company "Harmoniya krasy"
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust - St Thomas' Hospital
city: London
country: United Kingdom
facility: St George's University Hospitals NHS Foundation Trust - St George's Hospital
Study officials:
affiliation: Keck School of Medicine, University of Southern California
name: Toby Maher, MD
role: PRINCIPAL_INVESTIGATOR
References: