COVID-19 respiratory disease MedDRA version: 23.0 Level: LLT Classification code 10084270 Term: SARS-CoV-2 acute respiratory disease System Organ Class: 100000004862
Conditions
Interventions
Product Name: Deupirfenidone
Product Code: LYT-100
Pharmaceutical Form: Capsule
INN or Proposed INN: Not yet available
CAS Number: 1093951-85-9
Current Sponsor code: deupirfenidone or d3-pirfenidone (
Sponsors
PureTech LYT 100, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible for this study, participants have to meet all of the following inclusion criteria: Inclusion Criteria - Part A: 1. 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) 2. 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 3. Written, electronic, or oral informed consent from the patient or Legally Authorized Representative prior to any study procedures in a manner approved by an IRB or Ethics Committee 4. Male or female, aged =18 to =80 years of age, inclusively at the time of informed consent 5. Able to perform and willing to comply with all study procedures and requirements 6. Able to bear weight and ambulate a minimum of 10 m distance (use of inhaled oxygen permitted) 7. Randomization day is dependent on type of qualifying respiratory support and date of initial confirmed COVID-19 diagnosis as described in Table 1. 8. COVID-19 pneumonia findings on imaging (chest X-ray or CT Scan) with a minimum of two lung lobes involvement 9. Shortness of breath = grade 3 on mBDS dyspnea scale 10. Laboratory parameters (CBC, biochemistry) deemed by the investigator as acceptable and/or not clinically significant to enroll the patient 11. Women of childbearing potential (WOCBP) must be non-pregnant and non-lactating, and must be abstinent from heterosexual intercourse for 90 days following last dose of study medication or agree to use one of the acceptable, highly effective double contraception: a. oral, intravaginal, or transdermal combined (estrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation b. oral, injectable, or implantable progestogen-only hormonal contraception associated with inhibition of ovulation c. intrauterine device (IUD) 12. Male patients must be surgically sterile (> 30 days since vasectomy with no viable sperm), abstinent, or if engaged in sexual relations with a WOCBP, the participant and his partner must be surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or using an acceptable, highly effective contraceptive method from screening until study completion, including the follow-up period and an additional 90 days after the last dose of study medication 13. Males will not donate sperm for at least 90 days after the last dose of study medication 14. Partners of male patients and female patients will report pregnancy occurring within 90 days from cessation of study medication 15. Patients can be on other medication (on and off label), apart from the ones specifically outlined in the Exclusion Criteria, to treat COVID-19 respiratory disease, that the investigator deems clinically relevant in combination with the study drug 16. Patients can concomitantly receive any standard of care as per investigators’ clinical decision; standard of care may encompass any approved medication, on or off label apart from the ones specifically outlined in the exclusion criteria. Concomitant medication may be other medication(s) apart from the ones specifically outlined in the Exc
Exclusion criteria
Exclusion criteria: Exclusion Criteria - Part A: 1. Patients who cannot f-up with study participation requirements 2. Investigator considers patient is inappropriate to enroll in the trial 3. 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 4. 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 min, prior to confirmed COVID-19 diagnosis 5. Co-morbid diagnosis of tuberculosis 6. Unstable angina or myocardial infarction in the last month prior to screening 7. Pre-existing co-morbidity associated with life expectancy less than 1 year 8. Present life expectancy less than 3 days and/or LDH >360 9. Body mass index =50 kg/m2 10. Resting heart rate of = 120 bpm, systolic BP of >180 mm Hg and a diastolic BP of >100 mm Hg and/or or a fall in pulse oximetry oxygen saturation (SpO2) to <80% upon ambulation 11.Sepsis,septic/hypovolemic/cardiogenic/neurogenic shock 12. Patients on MV, ECMO, NIV, HFNO and/or other high flow oxygen FiO2 =35% and =8 lpm within the last 72 hrs prior to screening. Low flow supplemental oxygen is allowed 13. History of anaphylactic reaction (particularly reactions to general anesthetic agents); allergic reaction due to any drug which led to significant morbidity; prior allergic reaction to pirfenidone 14. Known symptoms of dysphagia or known difficulty in swallowing capsules and/or total gastrectomy 15. Patients undergoing dialysis or hemoperfusion, or with a history of, or anticipated to require dialysis or hemoperfusion within 72 hrs of screening or severe renal impairment (defined as creatinine clearance rate <30 mL/min) at the time of screening/ baseline 16. Use of any of the following drugs: a. Fluvoxamine, enoxacin, ciprofloxacin b. Treatment with steroids under institutional protocols and guidelines to manage COVID-19 pneumonia/respiratory symptoms is allowed. Use of steroids off-label to treat non-COVID-19 related conditions is not allowed c. Any Investigational Agents (i.e., non-approved or nonauthorized drugs), except those used for COVID-19 resp. diseases that the investigator deems clinically relevant in combination with the study drug, as described below: i. Allowed agents • Patients who had received prior investig. agents for COVID-19 but are no longer taking those drugs - allowed • Inhaled corticosteroids - allowed • Patients that received prior convalescent plasma - allowed; however concomitant convalescent plasma is excluded ii. Excluded agents Patients on concomitant experimental anti-viral, anti-fibrotic or anti-inflammatory therapies are excluded. Any investig. agent not explicitly on this list should be reviewed by the medical monitor prior to initiating therapy or enrolling participant d. Other inhibitors of CYP1A2 (including but not limited to methoxsalen or mexiletine). e. Inducers of CYP1A2 (phenytoin), CYP2C9 or 2C19 (including but not limited to carbamazepine or rifampin) f. Drugs associated with substantial risk for prolongation of the QTc interval (including but
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Study Objectives- Part A To evaluate the effect of LYT-100 on the change in distance walked on the six-minute walk test performed in line with the American Thoracic Society/European Respiratory Society Guidelines. Study Objectives- Part B To assess the longer-term safety, tolerability, and efficacy of LYT-100 through up to 182 days of treatment. ;Secondary Objective: Key Second. Obj: To evaluate the effect of 91 days of treatment with LYT-100 compared to placebo on the Modified Borg Dyspnoea Scale (mBDS). Other Second. Obj: To evaluate the effect in Part A: of 91 days of treatment with LYT-100 compared to placebo Part B: up to 182 days of treatment with LYT-100 1. SGR Questionnaire-I (SGRQ-I) 2. Dyspnoea-12 3. The WHO Ordinal Scale for Clinical Improvement 4. QoL assessment as collected using the SF-36 (v2) 5. Number of lung segments involved using CT Scan and QLF assessment 6. Inflammatory, fibrosis and other biomarkers 7. Pulmonary exacerbations, severe and non-severe 8. All-cause rehospitalizations 9. Severity of lung lobe(s) involvement, using CT Scan 10. Pulse oximetry 11. Chest X-ray 12. Length of hospital stay 13. All-cause mortality 14. Use of supplemental oxygen from Baseline to end of treatment 15. Change in distance walked on the six-minute walk test (only part B) 16. The mBDS Scale (only part B);Primary end point(s): Primary efficacy endpoint - Part A: 6-minute walk test (6MWT) is the primary efficacy endpoint. All patients will complete a 6MWT test according to the Schedule of Assessments and aligned with the American Thoracic Society/European Respiratory Society Guidelines with COVID-19 modifications provided in the 6MWT study procedural manual. The 6MWT measures the distance a patient can quickly walk on a flat, hard surface in a period of 6 minutes. It evaluates the global and integrated response of all the systems involved during exercise. This is a self-paced test. Patients choose their own intensity of exercise and may stop and r | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: All efficacy endpoints will be derived at each protocol-schedule time point for which they are collected, with analysis performed (e.g. change from baseline) for each time point. The efficacy endpoints are consistent with the primary and secondary objectives of the study.;Secondary end point(s): Key Secondary efficacy endpoints - PART A: • Modified Borg Dyspnoea Scale (mBDS) is a measure of dyspnea. The mBDS is a self-administered unidimensional assessment tool that analyzes breathlessness under exertion. Changes over time will be derived. Other Secondary and Exploratory Efficacy Endpoints: • 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. Changes from baseline in the component scores of the SGRQ-I will be assessed. • Dyspnoea-12 (D-12) is an instrument used to assess the effect of dyspnea in interstitial lung disease and COPD, and is used in reference to the patient’s breathlessness experience “these days”, i.e., current at baseline and at follow-up visits, and unlike other dyspnea tools, it has no reference to activity. The tool has 12 descriptor items ranging from none (0), mild (1), moderate (2) or severe (3). An overall score of breathlessness severity is provided that encompasses seven physical items and five affective items. Total scores range from 1 to 36 whereby severity correlates with greater severity. • WHO Ordinal Scale for Clinical Improvement will be assessed for changes from baseline over time. The WHO ordinal scale has the following nine categories: (0) Uninfected (No clinical or virological evidence of infection); (1) Ambulatory (No limitation of activitie | — |
Countries
Argentina, Brazil, Moldova, Republic of, Philippines, Romania, Ukraine, United Kingdom, United States
Contacts
Public ContactHeather Paden
PureTech LYT 100, Inc.
Outcome results
None listed