To Study the Effect, Safety and Tolerability of Resmetirom Tablets in adult participants in conjunction with diet and exercise for the treatment in Non-cirrhotic Non-alcoholic Steatohepatitis (NASH) with moderate to advanced liver fibrosis.
Scientific Title of Study
A Multicenter, Randomized, Double blind, Parallel Group, Placebo Controlled, Phase III Clinical Study to Evaluate the Efficacy, Safety and Tolerability of Resmetirom Tablets versus Placebo Tablets in adult participants in conjunction with diet and exercise for the treatment in Non-cirrhotic Non-alcoholic Steatohepatitis (NASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis).
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
BCR-RAV-003 Version No- 2.0 Dated 17-Apr-2025
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Dawesh Prakash Yadav
Designation
Principal Investigator
Affiliation
Institute of Medical Sciences, Banaras Hindu University
Address
Department of Gastroenterology, Room No-23, 2nd Floor, CSSB Building, Sir Sunderlal Hospital, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
Varanasi UTTAR PRADESH 221005 India
Phone
918130856563
Fax
Email
devesh.thedoc@gmail.com
Details of Contact Person Scientific Query
Name
Dr Neeta Nargundkar
Designation
Managing Director
Affiliation
Biosphere Clinical Research Pvt Ltd
Address
Biosphere Clinical Research Pvt. Ltd.
SB-02, 03 and 04, Second Floor Highland Corporate Centre, Kapurbawdi Junction, Thane West Maharashtra, India
Thane MAHARASHTRA 400607 India
Phone
02241006794
Fax
Email
drneeta@biospherecro.com
Details of Contact Person Public Query
Name
Dr Neeta Nargundkar
Designation
Managing Director
Affiliation
Biosphere Clinical Research Pvt Ltd
Address
Biosphere Clinical Research Pvt. Ltd.
SB-02, 03 and 04, Second Floor Highland Corporate Centre, Kapurbawdi Junction, Thane West Maharashtra, India
Department of Medicine, Division of General Medicine , Room number-62, Ground Floor, Dr. B R Ambedkar Road, Sadashiv Nagar Belagavi-590001, Karnataka, India Belgaum KARNATAKA
8088907430
prashanth.jaikar@gmail.com
Dr Ajay Kumar
King Georges Medical University
Department of Medicine, Division of gastro unit, Gandhi ward, Room No. 201, 1st floor, King Georges Medical University, Shahmeena Road, Chowk, Lucknow, Uttar Pradesh - 226003, India Lucknow UTTAR PRADESH
9455519306
drajaymd12345@gmail.com
Dr Arun K Valsan
Amrita Institute of Medical Sciences and Research Centre
Dept. of Gastroenterology and Hepatology, AIMS Ponekkara P.O, Kochi-682041 India Ernakulam KERALA
8411051156
arunvalsan@aims.amrita.edu
Dr Saurabh Kaushik
Gangasheel Advanced Medical Research Institute
Department of Gastroenterology, Room No-116, 1st Floor, C-17, Deen Dayal Puram, Bareilly-243122, Uttar Pradesh, India Bareilly UTTAR PRADESH
8700721469
drsaurabhkaushik@gmail.com
Dr Ashok Rohidas Mohite
GI-One Hospital
Department of Gastroenterology, Ground floor, Amrut Sai Solitaire, Besides Goldie Cinema, Railway Station Road, Aurangabad-431005, Maharashtra, India.
Aurangabad MAHARASHTRA
9309366806
armohitecr@gmail.com
Dr Anumula Kavitha
Government General Hospital
Department of Gastroenterology, 2nd Floor, Room no: 220, GMCANA Building, GMC/GGH, Railpet, Guntur, Andhra Pradesh, India. Guntur ANDHRA PRADESH
9399977555
jananigastro@ymail.com
Dr Manish Bhatnagar
ICON Hospital
Department of Gastroenterology, Room No-301, 3rd floor, Lake, Beside Kalyan Pushti Haveli Opp. Alpha One (Ahmedabad One) Mall, Exit, near Vastrapur, Vastrapur, Ahmedabad, Gujarat 380015. Ahmadabad GUJARAT
9825085059
bhatnagarclinic@yahoo.com
Dr Rakhi Maiwall
Institute of Liver and Biliary Sciences
Department of Hepatology, Division of Liver, Room No.3328, 3rd Floor, DI, Vasant Kunj Road, Ghitorni, New Delhi, Delhi- 110070 New Delhi DELHI
8750343085
rakhi_2011@yahoo.co.in
Dr Dawesh Prakash Yadav
Institute of Medical Sciences, Banaras Hindu University
Department of Gastroenterology, Room No-23, 2nd Floor, CSSB Building, Sir Sunderlal Hospital, Varanasi- 221005, Uttar Pradesh, India Varanasi UTTAR PRADESH
8130856563
devesh.thedoc@gmail.com
Dr Prasenjit Halder
IPGME and R, SSKM Hospital
Department of Gastroenterology, Division of SDLD, 4th floor, 244, A.J.C. Bose Road, Kolkata - 700020, West Bengal, India
Kolkata WEST BENGAL
8420529580
prasenjit0024@gmail.com
Dr Dhaval Dave
Jupiter Hospital and Research Centre
Department of Clinical Research, Shop No. 9 Ground Floor, Opp. ICAI Bhavan, Sun Pharma - Atladra Road,
Atladara, Vadodara, Gujarat-390012
Vadodara GUJARAT
8238022292
drdhavaldavenm@gmail.com
Dr Aravind K
Karnataka Medical College and Research Institute
Department of Surgical Gastroenterology, 2nd Floor, PMSSY Building, Old PB Road, Vidyanagar, Hubballi, -580022, Karnataka, India. Dharwad KARNATAKA
9448241787
drkaravind@gmail.com
Dr Santosh Dhananjay Hajare
KLES Dr Prabhakar Kore Hospital and MRC
Department of Gastroenterology, OPD 33, Ground plus 2nd Sharavati Floor, Nehru Nagar, Belagavi-590010 Karnataka, India Belgaum KARNATAKA
9448111913
drsantoshhajare@gmail.com
Dr Kaushlendra Nath Tripathi
Motilal Nehru Medical College and Associated with Swarooprani Nehru Hospital
Department of Medicine Motilal Nehru Medical College & Associated with Swarooprani Nehru Hospital Prayagraj, Uttar Pradesh – 211002, India.
Allahabad UTTAR PRADESH
7007486535
kaushlendranathtripathi@gmail.com
Dr Kamleshkumar Magnani
Nand Multispeciality Hospital
Department of Gastroenterology, 1st Floor, Room No-101, Near Panchmukhi Hanuman Temple, Vasana- Bhayali Road, Next to Shantidham society, Vadodara-390015, Gujarat, India. Vadodara GUJARAT
9625196109
drkamleshmagnaniicr@gmail.com
Dr Yogesh Harwani
Noble Gastro and Liver Hospital
Department of Gastroenterology, OPD Room, 5th and 6th Floor, Mithakhali Six Rd, opp. Nalanda Hotel, Mithakhali, Ellisbridge, Ahmedabad, Gujarat 380009 Ahmadabad GUJARAT
8141655955
dryogeshncr@gmail.com
Dr Vinay Kumar
Postgraduate Department of Medicine GSVM Medical College
Department of Medicine, Room No.12, Post Graduate Department of Medicine, GSVM Medical College, Kanpur-208001, Uttar Pradesh, India. Kanpur Nagar UTTAR PRADESH
8004877113
dr.vinayksachan@gmail.com
Dr Rajanikant R Yadav
Sanjay Gandhi Post Graduate Institute of Medical Science
Department of Radiodiagnosis, 2nd Floor, Raebareli Road, Lucknow-226014, India Lucknow UTTAR PRADESH
8004904493
rajani24478@gmail.com
Dr Kapil Kumar Sharma
Sarvodaya Hospital and Research Centre
Department of Gastroenterology, Room No.1501, Ground Floor, Sector 8, YMCA Road,Faridabad-121006, Haryana, India Faridabad HARYANA
7023176653
drkapilkumarsharma83@gmail.com
Dr Shivam Gupta
Shri Ram Murti Smarak Institute of Medical Sciences
Department of Gastroenterology, Ground Floor, OPD No- 8, Ram Murti Puram,13km. Bareilly-Nainital Road, Bareilly-243202, Uttar Pradesh, India. Bareilly UTTAR PRADESH
7797558885
iamdrshivam@gmail.com
Dr Irshad Ali H
Sparsh Super Specialty Hospital
Department of Medical Gastroenterology, Division of Hepatology and Gastroenterology, Room No-17, Ground Floor, No. 4/1 Tumkur road, Yeshwanthpur, Bangalore-560022 Bangalore KARNATAKA
9606197707
researchsparsh@aol.com
Dr Lokesh L V
Sparsh Super Specialty Hospital
Department of Medical Gastroenterology, Division of Hepatology and Gastroenterology, Room No. 1, 1st floor, 146 Infantry Road, Opposite to police commissioners office Bangalore-560001, Karnataka, India Bangalore KARNATAKA
9606197707
Gastrosparsh@gmail.com
Dr Harshad Khairnar
Terna Speciality Hospital & Research Centre
Department of Clinical Research, 3rd floor, Room No-337, Phase II, Plot No-12, Sec-22, Opp. Nerul Railway Station, Nerul West, Navi Mumbai-400706, Maharashtra Thane MAHARASHTRA
8828208600
harshadkhairnar@yahoo.com
Dr Sanjay Kumar
The Medicity Hospital (A Unit of V3 Healthcare Private Limited)
Department of Medicine, Ground floor, Teen Pani, Kichha Road, Rudrapur, Udham Singh Nagar, Uttarakhand- 263153. Udham Singh Nagar UTTARANCHAL
9868080947
drsanjay0947md@gmail.com
Dr Pravin Rathi
TNMC NAIR HOSPITAL Topiwala National Medical College Nair Hospital
Department of Gastroenterology, Room No 714/715, 7th Floor, A L Nair Road, Mumbai Central Mumbai, Maharashtra- 400008, India Mumbai MAHARASHTRA
One tablet to be taken once daily with or without food, preferably at the
same time for 52 weeks (364 Days).
Intervention
Resmetirom 100 mg Tablet
One tablet to be taken once daily with or without food, preferably at the
same time for 52 weeks (364 Days).
Intervention
Resmetirom 60 mg Tablet
One tablet to be taken once daily with or without food, preferably at the
same time for 52 weeks (364 Days).
Intervention
Resmetirom 80 mg Tablet
One tablet to be taken once daily with or without food, preferably at the
same time for 52 weeks (364 Days).
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Male or Female participants greater than or equal to 18 years to less than or equal to 65 years.
2. Confirmed diagnosis of NASH fibrosis in participants who meet one of the following criteria that is consistent with NASH liver fibrosis: Historical biochemical test for fibrosis: N-terminal pro-peptide of type III collagen (PRO-C3) greater than 14 ng/mL or Enhanced liver fibrosis (ELF) greater than or equal to 9 or Fibroscan with transient elastography greater than or equal to 8.5 kPa and controlled attenuation parameter grater than or equal to 280 dB.m-1.
3. Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) greater than or equal to 8% obtained during the screening period.
4. Biopsy-proven NASH (baseline liver biopsy), based on a liver biopsy obtained within 3 months of randomization with fibrosis stage, F2 or F3 on liver biopsy and NAS of greater than or equal to 4 with a score of at least 1 in each of the following NAS components:
-Steatosis (scored 0 to 3)
-Ballooning degeneration (scored 0 to 2)
-Lobular inflammation (scored 0 to 3)
5. Participants who are willing to give informed consent for participation in the study and willing to adhere to all protocol procedures.
Cohort specific Inclusion Criteria:
Cohort I: Participants with a body weight of less than 60 kg.
Cohort II: Participants with a body weight between 60 to less than 100 kg.
Cohort III: Participants with a body weight of greater than or equal to 100 kg.
ExclusionCriteria
Details
1.Participants with a history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening.
2. Participants with regular use of drugs historically associated with NAFLD.
3. Participants with presence of cirrhosis on liver biopsy defined as stage 4 fibrosis (F4).
4. Participants with diagnosis of hepatocellular carcinoma (HCC).
5. Participants with hepatic decompensation.
6. Participants with chronic liver diseases other than NASH.
7. Participants whose Serum ALT greater than 250 U/L.
8. Participants with a diagnosis of type 2 diabetes mellitus with glycosylated hemoglobin (HbA1c) greater than or equal to 11.0%.
9. Participants with Estimated glomerular filtration rate (eGFR)less than 60 mL/min/1.73 m2 [using the Modification of Diet in Renal Disease (MDRD) equation] at screening.
10. Participants with Thyroid diseases:
- Active hyperthyroidism.
- Untreated clinical hypothyroidism defined by thyroid stimulating hormone (TSH) greater than 7 IU/L with symptoms of hypothyroidism or greater than 10 IU/L without symptoms.
- Participants who have had a thyroidectomy and are on replacement thyroxine doses greater than 75 µg per day are allowed.
11. Participants with known history of HIV, Hepatitis B and Hepatitis C.
12. Participants with history of any active autoimmune disease.
13. Participants with significant cardiovascular history defined as: myocardial infarction, unstable angina pectoris, transient ischemic attack, unstable or previously undiagnosed arrhythmia, cardiac surgery or revascularization (coronary angioplasty or bypass grafts), or cerebrovascular accident.
14. Participants with clinically relevant current or past history of severe, unstable, or uncontrolled pulmonary, hepatic and renal diseases.
15. Participants with history of bariatric surgery or intestinal bypass surgery within the 5 years prior to screening or planned during the conduct of the study.
16. Currently taking prohibited concomitant medications listed and inability/unwillingness to discontinue them for the entire study period.
17. Participants with active, serious medical disease with a likely life expectancy less than 2 years.
18. Any other health or mental condition or any significant laboratory parameters that in the investigators opinion may adversely affect the participants ability to complete the study or its measures or that may pose significant risk to the participant.
19. Concurrent participation in another clinical trial or any investigational therapy within 30 days prior to signing informed consent.
20. Female participants who are pregnant or lactating or planning to become pregnant during the study period. Females or males who are not ready to use acceptable contraceptive methods during the course of study.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
An Open list of random numbers
Blinding/Masking
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Primary Outcome
Outcome
TimePoints
Proportion with resolution of NASH (ballooning 0, inflammation 0,1) associated with at least 2-point reduction in NAFLD Activity Score (NAS) without worsening of fibrosis stage from baseline to end of study visit (Week 52).
Proportion with at least a 1-point improvement in fibrosis stage with no worsening of NAS from baseline to end of study visit (Week 52).
52 Weeks (364 Days)
Secondary Outcome
Outcome
TimePoints
Percentage change in the low-density lipoprotein from baseline to end of study visit (Week 52).
52 Weeks (364 Days)
Safety Parameter:
The assessment of safety will be based on the frequency of Adverse Events and Changes in laboratory parameters.
52 Weeks (364 Days)
Target Sample Size
Total Sample Size="210" Sample Size from India="210" 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
A Multicenter, Randomized, Double Blind, Parallel Group, Placebo Controlled, Phase III Clinical Study to Evaluate the Efficacy, Safety and Tolerability of Resmetirom Tablets versus Placebo Tablets in adult participants in conjunction with diet and exercise for the treatment in Non-cirrhotic Non-alcoholic Steatohepatitis (NASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis).
Primary objective:
To evaluate the efficacy of Resmetirom Tablets in adult participants in conjunction with diet and exercise for the treatment in Non cirrhotic Non-alcoholic Steatohepatitis (NASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis).
Secondary objective:
To evaluate the safety and tolerability of Resmetirom Tablets in adult participants in conjunction with diet and exercise for the treatment in Non-cirrhotic Non-alcoholic Steatohepatitis (NASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis).
Lifestyle modification with diet and exercise is to be followed for all the three cohorts.