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CTRI Number  CTRI/2025/07/090987 [Registered on: 16/07/2025] Trial Registered Prospectively
Last Modified On: 15/07/2025
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Placebo Controlled Trial 
Public Title of Study   The MANTRA Trial: Testing the Effectiveness and Safety of AD64 in People with Metabolic Dysfunction-Associated Steatohepatitis (MASH) 
Scientific Title of Study   A Phase II Proof-of-Concept Study Assessing the Efficacy and Safety of AD64 in Patients with Metabolic Dysfunction-Associated Steatohepatitis (MASH) 
Trial Acronym  NIL 
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Shiran Shetty 
Designation  Professor and Unit Head 
Affiliation  KMC Manipal 
Address  Deputy Medical Superintendent Professor and Unit Head Dept. of Gastroenterology and Hepatology Kasturba Medical College, Manipal

Udupi
KARNATAKA
576104
India 
Phone  8096938520  
Fax    
Email  shiran.shetty@manipal.edu  
 
Details of Contact Person
Scientific Query  
Name  Dr Shiran Shetty 
Designation  Professor and Unit Head 
Affiliation  KMC Manipal 
Address  Deputy Medical Superintendent Professor and Unit Head Dept. of Gastroenterology and Hepatology Kasturba Medical College, Manipal

Udupi
KARNATAKA
576104
India 
Phone  8096938520  
Fax    
Email  shiran.shetty@manipal.edu  
 
Details of Contact Person
Public Query  
Name  Dr Shiran Shetty 
Designation  Professor and Unit Head 
Affiliation  KMC Manipal 
Address  Deputy Medical Superintendent Professor and Unit Head Dept. of Gastroenterology and Hepatology Kasturba Medical College, Manipal

Udupi
KARNATAKA
576104
India 
Phone  8096938520  
Fax    
Email  shiran.shetty@manipal.edu  
 
Source of Monetary or Material Support  
Kasturba Medical college and Hospital, Department Gastroenterology, Room number 1, Tiger Circle Road, Madhav Nagar, Eshwar Nagar, Manipal, Karnataka, Udupi - 576104 
 
Primary Sponsor  
Name  Bioplus Life Sciences 
Address  Pharmed Gardens, Whitefield Main Rd, Sadara Mangala Industrial Area, Thigalarapalya, Krishnarajapuram, Bengaluru, Karnataka 560048 
Type of Sponsor  Pharmaceutical industry-Indian 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Shiran Shetty  Kasturba Medical college and Hospital  Department Gastroenterology, Room number 1, Tiger Circle Road, Madhav Nagar, Eshwar Nagar, Manipal, Karnataka 576104
Udupi
KARNATAKA 		 8861920517

shiran.shetty@manipal.edu 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Kasturba Medical College and Kasturba HospitalInstitutional Ethics CommitteeInstitutionalEthicsCommittee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: K760||Fatty (change of) liver, not elsewhere classified,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  AD 64  This is a 4-arm randomized, double-blind, placebo-controlled design, with patients receiving either AD64 500 mg, AD64 1000 mg or matching placebo twice daily of subjects to study groups using applicable randomization schedule that will be reviewed and approved by an independent statistician. 1. Participants: The trial will include adults with confirmed MASH as per EASL guidelines. 2. Randomization: An adequate number of patients will be screened to randomize in 2:2:1:1 ratio, 300 patients into four treatment groups 100 patients in AD64 500 mg BID, 100 patients in AD64 1000mg BID and 50 patients each on two placebo groups, to have approximately 300 patients completing the study from each treatment group 3. Dosing: Participants will receive either AD64 500 mg, AD64 1000 mg or matching placebo groups twice daily for 52 weeks 4. Duration: The treatment duration will be 52 weeks, with liver biopsies conducted at baseline and at the end of the study to assess histological changes  
Comparator Agent  Placebo  This is a 4-arm randomized, double-blind, placebo-controlled design, with patients receiving either AD64 500 mg, AD64 1000 mg or matching placebo twice daily of subjects to study groups using applicable randomization schedule that will be reviewed and approved by an independent statistician. 1. Participants: The trial will include adults with confirmed MASH as per EASL guidelines. 2. Randomization: An adequate number of patients will be screened to randomize in 2:2:1:1 ratio, 300 patients into four treatment groups 100 patients in AD64 500 mg BID, 100 patients in AD64 1000mg BID and 50 patients each on two placebo groups, to have approximately 300 patients completing the study from each treatment group 3. Dosing: Participants will receive either AD64 500 mg, AD64 1000 mg or matching placebo groups twice daily for 52 weeks 4. Duration: The treatment duration will be 52 weeks, with liver biopsies conducted at baseline and at the end of the study to assess histological changes  
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  75.00 Year(s)
Gender  Both 
Details  1. Age 18 to 75 years
2. Diagnosis of MASH as per EASL guidelines
3. MRI PDFF fat fraction more than 8 percent obtained during the screening period (baseline MRI-PDFF) or a historic MRI PDFF less than or equal to 8 weeks old at the time of randomization.
4. Liver enzymes: Alanine transaminase and Aspartate transaminase levels less than or equal to 5 times upper limit of normal
5. Body mass index BMI 25 to 45 kg per meter square
6. Stable dyslipidemia therapy for more than 30 days prior to randomization.
7. Stable body weight: 5 percent for at least 3 months prior to screening
 
 
ExclusionCriteria 
Details  1. History of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening
2. Regular use of drugs historically associated with NAFLD
3. History of bariatric surgery or intestinal bypass surgery within the 5 years prior to randomization or planned during the conduct of the study.
4. Weight gain or loss more than total body weight within 12 weeks prior to randomization
5. HbA1c more than 9.0percent
6. Presence or history of hepatic decompensation eg ascites, variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis) or liver transplantation; hepatocellular carcinoma; and gastro-esophageal varices within the past 360 days before screening. Model for End-stage Liver Disease score more than or equal to 12, as determined at Screening unless due to therapeutic anti coagulation or Gilbert syndrome
7. Chronic liver diseases
8. Has an active autoimmune disease
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   On-site computer system 
Blinding/Masking   Double Blind Double Dummy 
Primary Outcome  
Outcome  TimePoints 
The proportion of patients achieving more than 30 percent relative reduction in hepatic fat on MRI PDFF at 12 and 36 weeks  The proportion of patients achieving more than 30 percent relative reduction in hepatic fat on MRI PDFF at 12 and 36 weeks 
 
Secondary Outcome  
Outcome  TimePoints 
To evaluate the safety & tolerability of the investigational medicinal product   52 weeks 
 
Target Sample Size   Total Sample Size="300"
Sample Size from India="300" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 2 
Date of First Enrollment (India)   01/09/2025 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="2"
Months="3"
Days="15" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   N/A 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary  

This is a 4-arm randomized, double-blind, placebo-controlled design, with patients receiving either AD64 500 mg, AD64 1000 mg or matching placebo twice daily of subjects to study groups using applicable randomization schedule that will be reviewed and approved by an independent statistician.

1.      Participants: The trial will include adults with confirmed MASH as per EASL guidelines.

2.      Randomization: An adequate number of patients will be screened to randomize in 2:2:1:1 ratio, 300 patients into four treatment groups 100 patients in AD64 500 mg BID, 100 patients in AD64 1000mg BID and 50 patients each on two placebo groups, to have approximately 300 patients completing the study from each treatment group

3.      Dosing: Participants will receive either AD64 500 mg, AD64 1000 mg or matching placebo groups twice daily for 52 weeks
Duration: The treatment duration will be 52 weeks, with liver biopsies conducted at baseline and at the end of the study to assess histological changes. 
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