CTRI/2021/12/038577 [Registered on: 10/12/2021] Trial Registered Prospectively
Last Modified On:
21/10/2022
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Other
Public Title of Study
A clinical trial to study safety and efficacy of Deupirfenidone (LYT-100) drug in post-acute COVID-19 patients.
Scientific Title of Study
A phase 2 Randomized, Double-blind, Placebo-controlled Trial and Open-Label Extension to Evaluate Safety and Efficacy of Deupirfenidone (LYT-100) in Post-acute COVID-19 Respiratory Disease.
Trial Acronym
NA
Secondary IDs if Any
Secondary ID
Identifier
2020-003210-13
EudraCT
LYT-100-2020-02, Amendment 5, Ver 6.0, April 27, 2021
Protocol Number
NCT04652518
ClinicalTrials.gov
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Anil K MBBS MD
Designation
Principal Investigator
Affiliation
Syngene International Ltd
Address
Human Pharmacology Unit, Tower 1, Ground Floor, Semicon Park, Electronics City, Phase 2, Hosur Main Road
Bangalore KARNATAKA 560100 India
Phone
9845519111
Fax
9128082820
Email
Anil.Dr@syngeneintl.com
Details of Contact Person Scientific Query
Name
Dr Ramesh Ks
Designation
Senior Manager Medical and Regulatory Affairs
Affiliation
Syngene International Ltd
Address
Clinical development,
Tower 1, Ground Floor, Semicon Park, Electronics City, Phase 2, Hosur Main Road
Bangalore KARNATAKA 560100 India
Phone
08028082722
Fax
9128082820
Email
Ramesh.Ks@syngeneintl.com
Details of Contact Person Public Query
Name
Dr Ramesh Ks
Designation
Senior Manager Medical and Regulatory Affairs
Affiliation
Syngene International Ltd
Address
Clinical development,
Tower 1, Ground Floor, Semicon Park, Electronics City, Phase 2, Hosur Main Road
Bangalore KARNATAKA 560100 India
Phone
08028082722
Fax
9128082820
Email
Ramesh.Ks@syngeneintl.com
Source of Monetary or Material Support
"PureTech LYT 100, Inc."
6 Tide Street, Suite 400, Boston, MA, 02210, USA
Primary Sponsor
Name
PureTech
Address
6 Tide Street, Suite 400, Boston, MA, 02210, USA
Type of Sponsor
Research institution
Details of Secondary Sponsor
Name
Address
NA
Countries of Recruitment
Ukraine Argentina Brazil India Philippines Republic of Moldova Romania United Kingdom United States of America
Sites of Study
No of Sites = 6
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Archana Bhat
Father Muller Medical College Hospital
Staff Room , Department of General Medicine, 6th Floor, General Ward Building,
Father Muller Medical College Hospital Kankanady, Mangalore-575002 Dakshina Kannada KARNATAKA
9591438216
archanaacharya24@gmail.com
Dr Akshay HM
JSS Hospital Mysore
CDSA-Center For Clinical Research Excellence,
Room Number 2222, Master Health Check Area, 2nd Floor,
JSS Hospital, MG Road Ramachandra Agrahara,
Mysuru- 570004,Karnataka,India Mysore KARNATAKA
9886222812
hmmakshay@gmail.com
Dr Pravin Soni
PCMCs PGI Yashwantrao Chavan Memorial Hospital
PCMCs PGI Yashwantrao Chavan Memorial Hospital, 2nd floor, HOD cabin, Dept of general medicine, Sant Tukaram Nagar, Pimpri, Pune- 411018 Pune MAHARASHTRA
9822057511
drpravinsoni18@gmail.com
Dr Subhrojyotib Bhowmick
Peerless Hospitex Hospital and Resesarch Center Ltd.
2nd floor, Quality and Clinical research department,
Peerless Hospitex Hospital and Research Center limited360,
Panchasayar, Kolkata-700094 Kolkata WEST BENGAL
9830204863
drsubhro@gmail.com
Dr Keyur Brahme
Sir Sayajirao General Hospital (SSG Hospital)
5th floor, ward No.05
Department of medicine,
New Emergency building,
Jail road,
Anandpura,
Vadodara-390001 Vadodara GUJARAT
9727729105
Keyurbrahme@gmail.com
Dr Vinayak Sawardekar
St. Georges Hospital
Ground floor, Nursing home, room no 13, Research Department, St. Georges Hospital,
PD Mello Road, Fort, CST, Mumbai- 400001 Mumbai MAHARASHTRA
9880747703
vinayaks1812@gmail.com
Details of Ethics Committee
No of Ethics Committees= 6
Name of Committee
Approval Status
Father Muller Institutional Ethics Committee Mangalore
Submittted/Under Review
Institutional Ethics Committee for Human Research (IEC HR), Medical College of Baroda & SSG Hospital Research Ethics Committee, Vadodara
Submittted/Under Review
Institutional Ethics Committee, GGMC Mumbai
Submittted/Under Review
Institutional Ethics Committee, JSS Medical College Mysuru
Approved
Institutional Ethics Committee, Yashwantrao Chavan Memorial hospital Pimpri, Pune
Submittted/Under Review
Peerless Hosipex Hospital and Research Center Ltd. Clinical Research Ethics Committee Kolkata
Submittted/Under Review
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: B972||Coronavirus as the cause of diseases classified elsewhere,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Deupirfenidone Capsules
(LYT-100) 250 mg
Dose: 250 mg
Frequency: 500 mg and 750 mg BID
Route of administration: Oral
Duration of therapy:
Day 1 to Day 3: LYT-100 500 mg BID or matching Placebo x 3 days
Day 4 through Day 91: LYT-100 750 mg BID or matching Placebo x 88 days
Day 91 through Day 93: 1LYT-100 500 mg BID x 3 days
Day 94 through Day 182:LYT-100 750 mg BID x 88 days
Comparator Agent
Placebo Capsules
(LYT-100) 250 mg
Dose: 250 mg
Frequency: 500 mg and 750 mg BID
Route of administration: Oral
Duration of therapy:
Day 1 to Day 3: LYT-100 500 mg BID or matching Placebo x 3 days
Day 4 through Day 91: LYT-100 750 mg BID or matching Placebo x 88 days
Day 91 through Day 93: 1LYT-100 500 mg BID x 3 days
Day 94 through Day 182:LYT-100 750 mg BID x 88 days
Inclusion Criteria
Age From
18.00 Year(s)
Age To
80.00 Year(s)
Gender
Both
Details
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 Exclusion Criteria.
Inclusion Criteria-Part B:
1. Patient must have completed Part A of the study, through Day 91 of treatment.
2. In the opinion of the Investigator, the patient is a good candidate for continued treatment.
ExclusionCriteria
Details
Exclusion Criteria-Part A:
1. Patients who cannot follow-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 minutes, 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 ≥ 45kg/m2
10. Resting heart rate of ≥ 120 bpm, systolic blood pressure of > 180 mm Hg and a diastolic blood pressure 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 or other high flow oxygen (FiO2 ≥35% and flow rate ≥ 8 lpm) within the last 72 hours prior to screening
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 dialysis or hemoperfusion, or anticipated to require dialysis or hemoperfusion within 72 hours 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), with the exception of those used for COVID-19 respiratory diseases that the investigator deems clinically relevant in combination with the study drug, as described below:
i. Allowed agents
• Patients who had received prior investigational agents for COVID-19 but are no longer taking those drugs are allowed.
• Inhaled corticosteroids are allowed.
• Patients that received prior convalescent plasma are 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 investigational 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 (such as 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 not limited to moxifloxacin, quinidine, procainamide, amiodarone, sotalol). Note that QTc prolongation is not an all / nothing drug effect, and specifically the administration drugs such as hydroxychloroquine do not preclude participation in this trial but does mandate measurement of the QTc every 6 hours until deemed necessary in accordance with investigator judgement
g. Vaccination with a live vaccine is not permitted during the period from 4 weeks prior to screening to 4 weeks after the last dose
h. Tobacco and nicotine products and/ or a positive a cotinine test at screening
i. Pirfenidone or nintedanib
17. Any other reason that, in the opinion of the Investigator, might interfere with the evaluation required by the study
18. For AST ≥2.5xULN, ALT ≥2.5xULN and/or total bilirubin >1.5xULN (in the absence of history of Gilbert syndrome and/or the absence of alkaline phosphatase ≥2xULN or clinical evidence of cholestasis), or severe hepatic impairment
19. Patients requiring surgery due to an acute onset condition prior to randomization.
20. Patients experiencing tachypnea. For the purposes of this study, tachypnea is defined as resting respiratory rate ≥ 25 per minute.
Exclusion Criteria-Part B:
Patients must not meet any of the exclusion criteria as listed for Part A.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
To evaluate the effect of LYT-100 on the change in distance walked on six-minute walk test (6MWT) performed as per the American Thoracic Society/European Respiratory Society Guidelines (Crapo et al 2002).
All patients will be treated up to 91 consecutive days during the study treatment period. Study assessments are at Days 14, 28, 56 and Day 91 ± 3 days.
Secondary Outcome
Outcome
TimePoints
To assess the longer-term safety, tolerability, and efficacy of LYT-100 through up to 182 days of treatment
Patients who complete 91 days of treatment in Part A and who are eligible may elect to participate in Part B. All patients will be treated in Part B up to 91 consecutive days, with study assessments on Days 91, 105, 119, 147 and 182.
Target Sample Size
Total Sample Size="168" Sample Size from India="80" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is 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 will be conducted in two parts, A and B. Part A is a phase 2 multi-centre randomized, double-blind, parallel arm, placebo-controlled study being conducted to evaluate the safety and efficacy of Study drug (LYT-100) compared to placebo in post-acute adult patients with COVID-19 respiratory disease who were treated with supplemental oxygen (including MV, ECMO 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. The second part of the study, Part B, is an open-label extension (OLE) in which eligible patients who completed Part A will be enrolled and treated with open-label study drug (LYT-100) for an additional 91 days.
The study will be performed in approximately 35 clinical sites in Europe, the US, Asia, South America, UK and LATAM.