A phase II trial to evaluate the efficacy and safety of Usnoflast for the treatment of participants with mild to moderately active Ulcerative Colitis not responding to or intolerant to oral aminosalicylates.
Scientific Title of Study
A study to evaluate the efficacy and safety of Usnoflast oral capsules for the treatment of participants with mild to moderately active Ulcerative Colitis not responding to or intolerant to oral aminosalicylates.
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
USNO.25.001,Version 1,dated 12 February 2025
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Deven Parmar
Designation
Chief Medical Officer & Head – Clinical R & D
Affiliation
Zydus Lifesciences Ltd
Address
Zydus Research Centre, Survey No. 396/403, Sarkhej-BavlaNational Highway No. 8A Moraiya
Ahmadabad GUJARAT 382213 India
Phone
02717665555
Fax
Email
dparmar@zydustherapeutics.com
Details of Contact Person Scientific Query
Name
Dr Kevinkumar Kansagra
Designation
Senior General Manager
Affiliation
Zydus Lifesciences Ltd
Address
Zydus Research Center,Survey No. 396/403, Sarkhej-Bavla National Highway No. 8A
Ahmadabad GUJARAT 382213 India
Phone
02717665555
Fax
Email
kevinkumarkansagra@zyduslife.com
Details of Contact Person Public Query
Name
Dr Suchi Shah
Designation
Senior Scientist
Affiliation
Zydus Lifesciences Ltd
Address
Zydus Research Center,Survey No. 396/403, Sarkhej-Bavla National Highway No. 8A
Ahmadabad GUJARAT 382213 India
Phone
02717665555
Fax
Email
suchi.shah@zyduslife.com
Source of Monetary or Material Support
Zydus Lifesciences Limited,Zydus Research Centre,Survey No. 396/403,Sarkhej-Bavla NationalHighway No. 8A Moraiya,Ahmedabad 382213, Gujarat, India
Primary Sponsor
Name
Zydus Lifesciences Limited
Address
Zydus Research Centre,Survey No. 396/403,Sarkhej-Bavla National Highway No. 8AMoraiya,Ahmedabad 382213, Gujarat, India
Dr. DY Patil Hospital, Sector-5, Ayyappa Mandir Road, Nerul, Navi Mumbai-400706, Maharashtra, India
Mumbai MAHARASHTRA
9099081133
dipakahire33@gmail.com
DrVaibhav Ganjewar
GI-One Institute of Gastroenterology and Hospital
Siddharth Arcade, Railway Station Rd, Vedant Nagar, Chhatrapati Sambhajinagar (Aurangabad), Maharashtra-431005, India.
Aurangabad MAHARASHTRA
7720035616
vaibhav.gastro@gmail.com
Dr Anumula Kavitha
Guntur Medical College & Government General Hospital
Room No. 220, 2nd Floor, GMCANA Building, Department of Gastroenterology, Government General Hospital, GMC/GGH, Guntur, Andhra Pradesh- 522001, India
Guntur ANDHRA PRADESH
9399977555
jananigastro@ymail.com
DrDhruv Shah
HCC Happiness Care and Cure Multispeciality Hospital LLP
748, 5th main, II stage, WCR, Near Modi Hospital, Mahalakshmipuram (Nagapura), Bangalore-560086, Karnataka, India Bangalore KARNATAKA
9945190666
kargastro@gmail.com
Dr Shiran Shetty A
Kasturba Medical College
Department of Gastroenterology & Hepatology, Kasturba Medical College, Manipal, Udupi- Hebri Road, Madhav Nagar, Manipal, Karnataka 576104, India.
Udupi KARNATAKA
Max Super Speciality Hospital (A Unit of Hometrail Buildtech Pvt. Ltd), Near Civil Hospital, Phase-6, Mohali, Punjab-160055, India. Rupnagar PUNJAB
9646999094
Nikhil.nadkarni@maxhealthcare.com
Dr Uday Nagesh Shivaji
Mazumdar Shaw Medical centre-Narayana Hrudayalaya Limited
Narayana Health City, # 258/A, Bommasandra Industrial Area, Anekal Taluk, Bangalore, Karnataka 560099, India.
Bangalore KARNATAKA
7204933468
UDAYNAGESH.SHIVAJI.DR@NARAYANAHEALTH.ORG
Dr Deshmukh Sharad Anna
Mediliv Multispeciality Hospital
5th Floor, Shreeji Bizz World Complex, Near Kathe Galli Signal, Nashik-422011, Maharashtra, India Nashik MAHARASHTRA
7038032499
drdeshmukh.research@gmail.com
Dr Sudarshan Narayan Patil
Medinova Super Speciality Hospital Pvt. Ltd’s, Shatabdi Hospital
Medinova Super Speciality Hospital Pvt. Ltd’s, Shatabdi Hospital, Suyojit City Centre, Opp Mahamarg Bus stand, Mumbai Naka, Nashik-422005, Maharashtra, India.
Nashik MAHARASHTRA
9975649901
drsudarshannpatil@gmail.com
DrNitin bhople
MGM Medical College and Hospital
MGM Medical College and Hospital, N-6, CIDCO, Aurangabad, Maharashtra, 431003, India.
Aurangabad MAHARASHTRA
9766138367
nitin.gastro@gmail.com
DrKaivan Shah
Navneet Memorial Hospital "SUSHRUSHA"
Opp. Sardar Patel Seva Samaj Hall, In the Lane Opp. Tele. Exchange, Navrangpura, Ahmedabad
Ahmadabad GUJARAT
153, Magarpatta City Road, Hadapsar, Pune, Maharashtra- 411013, India.
Pune MAHARASHTRA
9986003257
drkiranshinderesearch21@gmail.com
Dr Ramesh Kumar Bhashyakarla
Osmania General Hospital
Department of Gastroenterology , NPR Block , 1st floor Liver care Unit Osmania General Hospital, Afzalgunj, Hyderabad, Telangana, 500012, India
Hyderabad TELANGANA
9949043290
bhashyakarla_rk@yahoo.co.in
Dr Tarana Gupta
Pt. B.D Sharma Post Graduate Institute of Medical Sciences (PGIMS Rohtak)
Dept. of Medicine, Pt. B.D Sharma Post Graduate Institute of Medical Sciences Rohtak 124001, Haryana, India
Rohtak HARYANA
9914048899
taranagupta@gmail.com
Dr Hemant Kumar Gupta
Samvedna Hospital
B27/88G, New Colony Ravindrapuri Varanasi-221005 U.P. India
Varanasi UTTAR PRADESH
"Institutional Ethices Comittee D Y Patil Medical College Address: 5th floor, Department of Pharmacology, Padmashree Dr. D Y Patil Medical College and Research Center, Sector-5, Nerul, Navi Mumbai, Dist: Thane-400706, Maharashtra, India. "
Approved
"Institutional Ethics Committee, PGIMS UHS Rohtak, PGIMS UHS Rohtak Pt. BD Sharma, Post Graduate Institute Of Sciences PGIMS UHS Rohtak-124001 Rohtak Rohtak Haryana - 124001"
Approved
"Karnataka Gastro Center Ethics committee Address: Karnataka Gastro Center 748, 11th Cross, 5th Main, 2nd Stage West of Chord road, Mahalakshmipuram Bengaluru (Bangalore) Urban Karnataka - 560086 "
Bhakti Vedanta Hospital Ethics Committee Bhaktivedanta HEC office, Bhaktivedanta Hospital & Research Institute, Srishti Complex, Bhaktivedanta Swami Marg, Mira Road (E), Thane-401107, Maharashtra India.
Approved
Ethics Committee GMC and GGH, Address: Guntur Medical College Kannavari Thota Main Road Guntur Andhra Pradesh-522001 India.
Approved
Ethics Committee of Navneet Memorial Hospital, Navneet Memorial Hospital,Navneet Memorial Hospital Opp. Sardar Patel Seva Samaj Hall, Navrangpura Ahmedabad Gujarat - 380006 India
Approved
HCG Multi Specialty Ethics Committee Address: HCG Hospitals Mithakali six Roads, Ellisbridge, Ahmedabad Gujarat - 380006 India
Institutional ethics committee Osmania Medical College, Address: Osmania Medical College, Koti, Hyderabad, 500095 Telangana India
Approved
Institutional Ethics Committee (IEC), Max Super Speciality Hospital (A Unit of Hometrail Buildtech Pvt. Ltd), Near Civil Hospital, Phase-6, Mohali, Punjab-160055, India.
Approved
Institutional Ethics Committee, KLE University KLE Dr. Prabhakar Kore Hospital and MRC Nehru Nagar Belagavi (Belgaum) Karnataka -590010.
Approved
Leelavati Care Hospital Near Big Bazar College Road Nashik Maharashtra - 422005 India
Approved
MAHE Ethics Committee Manipal Academy of Higher Education manipal.edu bldg Madhav Nagar, Manipal Udupi Udupi Karnataka - 576104 India
Approved
MGM Ethics Comittee for Research on Human Subject MGM Medical College and Hospital N-6, CIDCO, Aurangabad Maharshtra-431003 India.
Approved
MGM Ethics Comittee for Research on Human Subject MGM Medical College and Hospital N-6, CIDCO, Aurangabad Maharshtra-431003 India.
Approved
Narayana Health Medical Ethics Committee Address: Narayana Hrudayalaya Limited, Narayana Health Hospital Health City, No. 258/A, Bommasandra Industrial Area Anekal Taluk Bengaluru Bengaluru (Bangalore) Rural Karnataka - 560099 India
Approved
Noble Hospital Institutional Ethics Committee Address: Noble Hospital Pvt Ltd Magarpatta City Road Pune Maharashtra - 411013 India
Samvedna Hospital, B-22/88 G New Ravindra Puri Colony, Varanasi, Uttar Pradesh - 221005 India
Approved
Sangini Hospital, Santorini Square, B/H Abhishree Complex Opp. Star Bazar Nr Jodhpur Cross Roads Satellite Ahmedabad Gujarat-380015 India
Approved
Shree Siddhivinayak Hospital Ethics Committee Shree Siddhivinayak Maternity And Nursing Home Unity Campus, Opposite K.T.H.M College Gangapur Road, Nashik Maharashtra - 422002 India
Approved
Yashoda Academy of Medical Education and Research Address: Yashoda Hospitals, Behind Hari Hara Kala Bhavan, SP Road, Secunderabad - 500003, Telangana, India.
Approved
Zydus Hospital Ethics Committee, Zydus Hospitals & Healthcare Research Pvt Ltd. Zydus Hospital Road, Near Sola Bridge S. G. Highway Thaltej Ahmedabad Gujarat - 380054 India.
1) Male and female participants aged 18 to 75 years, both inclusive.
2) Have had ulcerative colitis (UC) diagnosed at least 3 months prior to screening. The diagnosis of UC must be confirmed by endoscopic and histologic evidence.
3) Mild to Moderately active disease defined as total score of at least 4 on the mMS, endoscopy subscore of at least 2 and a rectal bleeding sub-score of at least 1.
4) Demonstrated an inadequate response to, loss of response to, or intolerance to any of the Oral aminosalicylates (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide) characterized by signs and symptoms of persistently active disease during a current or prior course of at least 4 weeks of treatment with above listed oral aminosalicylates in the opinion of investigator.
5)Women of childbearing potential and men must agree to use adequate birth control measures during the study. Acceptable methods of birth control in this study include sur-gical sterilization, intrauterine device, oral contraceptive, contraceptive patch, long-act-ing injectable contraceptive, partner’s vasectomy, double-barrier method (condom or diaphragm with spermicide) or abstinence for at least 4 weeks prior to study drug admin-istration, during study participation and for 30 days after their last dose of study drug.
6)All participants aged 45 years or over must have had a colonoscopy to screen for adenomatous polyps within 5 years of screening or must have had a colonoscopy at screening to assess for polyps.
ExclusionCriteria
Details
1)Diagnosis of Crohn’s disease or indeterminate colitis or the presence or history of a fistula consistent with Crohn’s disease.
2) Have positive test for C. difficile at screening. If C. difficile is positive, the participant may be treated and retested.
3) Participants who have an evidence of pathogenic bowel infection on screening at inves-tigator’s discretion.
4) History of recurrent or chronic infection (e.g., hepatitis B or C, syphilis, TB).
5) Laboratory test positive for HBsAg, HCV or HIV at screening
6) Participants who have any known allergy or sensitivity to investigational products or any of its component within 3 months of screening.
7) Participants who have donated blood or blood products within 3 months of screening.
Exclusion criteria related to concomitant medication
8) Have had treatment with cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil (MMF) within 16 weeks prior to screening.
9) History or planned concurrent treatment with biological agents (infliximab, ada-limumab, vedolizumab, and ustekinumab), immunosuppressive agents (e.g., azathio-prine, 6-MP, or methotrexate) or with lymphocyte-depleting therapies (e.g., Campath, anti-CD4, cladribine, rituximab, ocrelizumab, cyclophosphamide, mitoxantrone, total body irradiation, bone marrow transplantation, alemtuzumab, daclizumab), Janus kinase (JAK) inhibitor (e.g., Tofacitininb) within 7 days or 5 half-lives of medication (which-ever is longer) prior to randomization and systemic steroids (e.g., prednisolone) before 14 days of randomization.
10) History of treatment with an investigational agent within 5 half-lives of that agent prior to randomization.
11) History of treatment with rectal steroids within 2 weeks of screening.
12) Receipt of a live vaccine within 4 weeks prior to randomization.
13) Chronic use of therapies that strongly inhibit or induce CYP3A4 metabolism within 4 weeks prior to randomization.
Exclusion criteria related to general health
14) Clinically relevant cardiovascular, hepatic, neurological, pulmonary, ophthalmological, endocrine, psychiatric or other major systemic disease making implementation of the protocol or interpretation of the study difficult or that would put the participant at risk by participating in the study.
15) Pregnant or lactating women or women of childbearing potential who have positive serum beta HCG test at screening.
16) History of significant alcoholism or drug abuse within the past 1 year. History or presence of significant smoking (more than 10 cigarettes per day) or consumption of tobacco/nicotine products (more than 10 times per day).
17) Participants who have participated in any drug research study other than the present trial within past 3 months
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Pre-numbered or coded identical Containers
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
proportion of participants in clinical remission at Week 12, defined as an mMS score of 0 to 2, including: stool frequency subscore 0 or 1, rectal bleeding subscore 0 and centrally read endoscopy score 0 or 1.
Baseline to week 12
Secondary Outcome
Outcome
TimePoints
Proportion of participants achieving clinical response
Week 12 and Week 24
Proportion of participants in clinical remission
Week 24
Proportion of participants in endoscopic remission
Week 12 and Week 24
Proportion of participant requiring rescue therapy (Steroid/biological agent) during the trial
Baseline to EOT
Mean change in biomarker fecal calprotectin
Baseline to week 12 & week 24
The incidence and type of AEs, SAEs, AEs leading to discontinuation of study treatment, target AEs of spe-cial interest, laboratory abnormalities, vital signs, ECG, and physical examination abnormalities
Baseline to EOT
Target Sample Size
Total Sample Size="129" Sample Size from India="129" 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="0" Days="0"
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 randomized, double blind, double dummy, parallel, placebo-controlled, phase II clinical trial to evaluate efficacy and safety of Usnoflast oral capsules for the treatment of mild to moderately active ulcerative colitis in participants not responding to or intolerant to oral aminosalicylates.
This trial will be conducted over a period of 29 weeks. Treatment period consist of two periods: induction period of 12 weeks followed by an open label maintenance period of 12 weeks. In this study, eligible participants will be enrolled in either of the following three arms (randomized 1:1:1) for induction period twice daily for 12 weeks.
Subjects will receive any of test regimen [50 mg (Arm 1), 75 mg (Arm 2), matching placebo (Arm 3)] as per randomization schedule for 12 weeks. At the end of 12 weeks, subjects will be assessed for achievement of clinical remission for primary end point assessment..