A phase II Clinical trial of Itolizumab for the induction of remission in biologics naïve patients with moderate to severely active ulcerative colitis
Scientific Title of Study
A phase 2 randomized, double-blind, parallel-group, placebo and active-controlled, two treatment period study to evaluate the safety and efficacy of Itolizumab for the induction of remission in biologics naïve patients with moderate to severely active ulcerative colitis
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
BIO-ITOLIZ-207, Ver.1.0, Dated 11-May-2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Ankit Ranpura
Designation
Senior Director
Affiliation
Biocon Biologics Limited
Address
Biocon House, Semicon Pak, Electronic city, Bangalore 560100
Bangalore KARNATAKA 560100 India
Phone
8460062870
Fax
Email
ankitkumar.ranpura@biocon.com
Details of Contact Person Scientific Query
Name
Dr Ankit Ranpura
Designation
Senior Director
Affiliation
Biocon Biologics Limited
Address
Biocon House, Semicon Pak, Electronic city, Bangalore 560100
Bangalore KARNATAKA 560100 India
Phone
8460062870
Fax
Email
ankitkumar.ranpura@biocon.com
Details of Contact Person Public Query
Name
Ms Jayanti Panda
Designation
Senior Director
Affiliation
Biocon Biologics Limited
Address
Biocon House, Semicon Pak, Electronic city, Bangalore 560100
Bangalore KARNATAKA 560100 India
Phone
08028085304
Fax
Email
Jayanti.Panda@biocon.com
Source of Monetary or Material Support
Biocon Limited, 20th KM, Hosur Road, Electronic City,
Bengaluru- 560100, Karnataka, India
Primary Sponsor
Name
Biocon Limited
Address
20th KM, Hosur Road, Electronic City,
Bengaluru- 560100, Karnataka, India
Amrita Institute of Medical Sciences & Research Centre,
Room # 1 Department of Gastroenterology Amrita Institute of Medical Sciences & Research Centre,
Ponekkara P.O., Kochi, Kerala, India 682041.
Kozhikode KERALA
9497556339
shines1560@aims.amrita.edu
Dr Rupa Banerjee
Asian Institute of Gastroenterology
AIG Hospitals (A unit of Asian Institute of Gastroenterology Hospitals)
Department of clinical research, Room No. 2
IBD Department, 6th floor IBD Centre
Plot No 2/3/4/5, Survey No 136, 1, Mindspace Rd,
Gachibowli, Hyderabad, Telangana 500032 Hyderabad TELANGANA
9849287530
rupabanerjee.aig@gmail.com
Dr Ajit Sood
Dayanand Medical College & Hospital
Department of Gastroenterology,
Dayanand Medical College & Hospital
Tagore Nagar, Civil Lines, Ludhiana-141001, Punjab, India Ludhiana PUNJAB
9815400718
ajitsood10@gmail.com
Dr Vinay Kumar
Ganesh Shankar Vidyarthi Memorial Medical College
Room # 21, Department of Medicine, Ganesh Shankar Vidyarthi Memorial Medical College, Swaroop Naga, Kanpur, Uttar Pradesh, India 208002, Kanpur Nagar UTTAR PRADESH
Maharaja Agrasen Hospital, OPD-3 Department of Gastroenterology, West Punjabi Bagh, New Delhi – India 110026 New Delhi DELHI
9811028897
drvivekbhatia@yahoo.co.in
Dr Ishan Shah
Navneet Memorial Hospital "SUSHRUSHA
Navneet Memorial Hospital "SUSHRUSHA, opp Sardar Patel Seva Samaj Hall , In Lane, Opp. Telephone Exchange, off CG Road, Navarangpura Ahmedabad - 380006 Ahmadabad GUJARAT
9599555795
docishanshah@gmail.com
Dr Nikhil Jillawar
Ojas Multispeciality Hospital
Clinical Research Department, Ojas Multispeciality Hospital
Sr. No203/1 Bhondave Chowk,
DY Patil College Road,
Ravet Pune, Maharashtra, India 412101
Pune MAHARASHTRA
9099058141
nikhiljillawar@gmail.com
Dr Aejaz Habeeb
Origin Hospital
Origin Hospital
2-5-36/CLRD/1 Chintalmet X Road Rajendra Nagar
(M) Ranga Reddy Hyderabad Hyderabad Telangana -
500048 India Hyderabad TELANGANA
9848034860
aejazhabeeb@hotmail.com
Dr Keyur Seth
Priyadarshani Nurshing Home,
Department of Gastroenterology,
1st to 3rd Floor, OPD 1 -3, Priyadarshani Nurshing Home, M-Baria Estate, Kargil Nagar Road, Opp. Manvel Pada Talav, Virar (East), Thane - 401305 Thane MAHARASHTRA
9930553321
itsdr@hotmail.com
Dr Maindad Dadasaheb Gajendra
Pulse Multispecialty Hospital
OPD-2, Departement of Gastroenterology Pulse Multispecialty Hospital
Sr. No. 51/7/B/1 1st floor,Vishwa Arcade,Opp Deccan Pavilion Hotel,Mumbai-Bangalore Highway, Narhe, Ambegaon, Pune – Maharashtra, India 411041
Pune MAHARASHTRA
9970126406
drmaindad.pulse@gmail.com
Dr Mukesh Kalla
S. R. Kalla Memorial Gastro & General Hospital
S. R. Kalla Memorial Gastro & General Hospital
78-79 Dhuleshwar Garden Behind HSBC Bank
Sardar Patel Marg C-Scheme Jaipur-302001
Rajasthan India Jaipur RAJASTHAN
9636237979
drmkalla@rediffmail.com
Dr Naresh Bansal
Sir Ganga Ram Hospital
Sir Ganga Ram Hospital,
Institute Of Liver Gastroenterology & Pancreatico Biliary Sciences,Room No.F-92,Old Rajinder Nagar ,
New Delhi, India – 110060
New Delhi DELHI
8447542860
drnbansal@gmail.com
Dr Rajiv Mehta
Surat Institute of Digestive Sciences
Surat Institute of Digestive Sciences
Vijay Nagar Gate # 03, Besides Nirman Bhavan,
Opposite Gandhi College, Surat-395002, Gujarat, India Surat GUJARAT
9879863510
rmgastro@yahoo.com
Dr Manoj Lahoti
Suyash Institute of Medical Sciences
Suyash Institute of Medical Sciences OPD-1, Gastroenterology Department, Unit 2,Gudhiyari Road, Near Avinash Lifestyle Tower, Behind Hotel Piccadily, Kota, Raipur, Chhattisgarh, India 492001 Raipur CHHATTISGARH
9826851120
manojlahoti24@gmail.com
Dr Sanjay Chandnani
TNMC BYL Nair Hospital
TNMC BYL Nair Hospital, Anand Rao, Nair Road, Mumbai Central East, Mumbai 400008 Mumbai MAHARASHTRA
Drug Trial Ethics Committee (DTEC), Dayanand Medical College & Hospital Civil Lines, Ludhiana (Pb.) 141001, Punjab, India.
Approved
Ethics Committee GSVM Medical College, Swaroop Naga, Kanpur-208002, Uttar Pradesh India
Approved
Ethics Committee of Pulse Multispeciality Hospital. Mumbai-Bangalore Highway, Narhe, Ambegaon, Pune – 411041
Approved
Institutional Ethics Committee Amrita Institute of Medical Sciences & Research Centre Amrita Institute of Medical Sciences & Research Centre, Ponekkara P.O., Kochi 682041
Approved
Institutional Ethics Committee Asian Institute of Gastroenterology, Hyderabad – 500082, Telangana, India
Approved
Institutional Ethics Committee, New Healthcare Nursing Home, Thane
SR Kalla Memorial Ethics Committee for Human Research, S. R. Kalla Memorial Gastro & General Hospital 78-79 Dhuleshwar Garden Behind HSBC Bank Sardar Patel Marg C-Scheme Jaipur-302001 Rajasthan India
Approved
Surat Institute of Digestive Science Ethics Committee, Surat 395002, Gujrat
Approved
Suyash Hospital Institutional Ethics Committee Suyash Institute of Medical Sciences, Gudhiyari Road, Piccadily, Kota, Raipur, Chhattisgarh 492001
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: K928||Other specified diseases of the digestive system,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Itolizumab
Dose:
Treatment Period 1
140 mg (1.4mL) SC every two weeks starting from Day 1 then Week 2, 4, 6, 8, 10
Treatment Period 2
140 mg (1.4mL) SC every two weeks on Week 12, 14, 16, 18, 20, 22
Administration: Subcutaneous injection.
Comparator Agent
Placebo & Adalimumab
Dose:
Treatment Period 1
140 mg (1.4mL) SC every two weeks starting from Day 1 then Week 2, 4, 6, 8, 10
Treatment Period 2
140 mg (1.4mL) SC every two weeks on Week 12, 14, 16, 18, 20, 22
Administration: Subcutaneous injection.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1.Male or female, 18 years of age or older with diagnosis of moderate to severe active UC confirmed by endoscopy and histologic evidence at least 6 months prior to screening visit, as defined by a Mayo score
2.Patients naïve to biologic therapy (e.g., TNF antagonist) and have a prior OR current UC medication history.
3.Before the first administration of study drug, the following conditions must be met
a.If receiving conventional immunomodulators (i.e., 6-MP or Azathioprine), must have been taking them for ≥12 weeks, and on a stable dose for at least 4 weeks.
4.A female patient has been sterilized or has been menopausal, or the patient has no pregnancy plan during the trial and voluntarily adopts effective contraceptive measures.
5.Able to comprehend the full nature and purpose of the study, including possible risks and side effects, and able to comply with all requirements of the study. Must be able to understand and voluntarily sign an informed consent prior to any study procedures.
ExclusionCriteria
Details
1.Patient with Crohn Disease, indeterminate colitis microscopic colitis, ischemic colitis, or radiation induced colitis, based on medical history, endoscopy, and or histological findings or presence or history of fistula with Crohn Disease or current evidence of fulminant colitis
2.History of pancolitis for less than or equal to 8 years or left-sided colitis less than or equal to 15 years.
3.Extensive colonic resection or colectomy or
imminent risk of colectomy, or prior history of toxic megacolon within 6 months of screening
4.History or current evidence of colonic dysplasia or adenomatous colonic polyps.
5.Active malignancy or carcinoma in situ within the last 5 years
6.Diagnosis of primary sclerosing cholangitis by liver function test.
7.Presence or history of active tuberculosis (TB) or latent TB infection,
8.Known acute or chronic viral hepatitis B or hepatitis C, or human immunodeficiency virus (HIV).
9.Other local or systemic pathological states requiring therapy with corticosteroids within 30 days prior to randomization except inhaled corticosteroids
10.Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination.
11.Does not agree to use contraception in the event of sexual activity for 130 days after the last dose of study drug if a female of childbearing potential or a male with a partner of childbearing potential.
12.Any serious inherited disorder, medical condition, or abnormality of clinical laboratory tests that, in the investigator judgment, precludes the patient safe participation in and completion of the study.
13.Evident renal disease or insufficiency, estimated glomerular filtration rate (eGFR) of <30 mL/min/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Proportion of participants who achieved clinical remission per Total Mayo Score
Week 12
Secondary Outcome
Outcome
TimePoints
Treatment Period 1
1. Proportion of Participants Who Achieved Clinical Response Per Total Mayo Score.
Week 12
2.Proportion of participants who Achieved Mucosal Healing.
Week 12
3.Proportion of Participants who achieved endoscopic remission.
Week 12
Treatment Period 2 – Participants who were responders at Week 12
1.Proportion who achieved clinical remission per Total Mayo Score.
Week 24.
2.Proportion who achieved Mucosal Healing
Week 24.
3. Proportion who achieved endoscopic remission.
Week 24
Who were non-responders at Week 12
1. Proportion who achieved clinical remission per Total Mayo Score.
Week 24
2. Proportion who achieved clinical response per Total Mayo Score
Week 24
3. Proportion who achieved Mucosal Healing.
Week 24
4. Proportion who achieved endoscopic remission.
Week 24
5. Proportion who achieved Histologic Remission
Week 24
Target Sample Size
Total Sample Size="90" Sample Size from India="90" Final Enrollment numbers achieved (Total)= "90" Final Enrollment numbers achieved (India)="90"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This study aims to evaluate the safety and efficacy of Itolizumab for induction of remission in biologics naïve patients with moderate to severely active UC.
Additionally, PK, biomarkers and immunogenicity will also be assessed.
Based on previous studies with Itolizumab in other inflammatory conditions for the rationale for dosing, we anticipate Itolizumab to have a positive impact on
patients with UC. As an indication UC has the advantage of possible early signals to support proof-of-concept (PoC). For the induction of remission in UC, a
12 week-trial usually provides meaningful information on the ability of a potential therapy to induce clinical and endoscopic remission. Depending on the
outcome of this PoC study, the safety and efficacy of Itolizumab can be further confirmed in a phase 3 trial in UC patients.