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

Phase 1

• Conditions: COVID-19 respiratory disease; MedDRA version: 23.0Level: LLTClassification code 10084270Term: SARS-CoV-2 acute respiratory diseaseSystem Organ Class: 100000004862; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2020-003210-13-RO
• Lead Sponsor: PureTech LYT 100, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-10-20
• Last Update Posted: 18 October 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 168

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 - 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified