Study Comparing the usefulness and safety of Etrolizumab Vs Placebo in patients with Ulcerative Colitis.
Scientific Title of Study
Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Evaluate The Efficacy (Maintenance Of Remission) And Safety Of Etrolizumab Compared With Placebo In Patients With Moderate To Severe Active Ulcerative Colitis Who Are Naive To TNF Inhibitors.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
GA29102, Version 5, 28-Aug-2015
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr B Vishwanath Tantry
Designation
Principal Investigator
Affiliation
Kasturba Medical College Hospital
Address
Manipal Centre for Clinical Research, Department of Gastroenterology, 7th Floor, Kasturba Medical College Hospital, Attavar, Mangalore
​146-B, 166 A, Unit No. 7, 8, 9, 8th Floor, R City Office, R City Mall, Lal Bahadur Shastri Marg, Ghatkopar, Mumbai - 400 086, Maharashtra, India
Countries of Recruitment
Argentina Austria Belgium Bulgaria Croatia Czech Republic Denmark Estonia France Germany India Italy Latvia Lithuania Netherlands Norway Poland Portugal Romania Slovakia Spain Sweden Ukraine United Kingdom United States of America
Sites of Study
No of Sites = 19
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Chetan Mehta
 Shree Giriraj Multispeciality Hospital
Department of Gastroenterology , 27-Navjyot Park Corner, 150 Feet Ring Road, Rajkot - 360 005, Gujrat, India Rajkot GUJARAT
9825077472
mehtacn@hotmail.com
Mohd Aejaz Habeeb
Deccan College of Medical Sciences
Centre for Liver Research and Diagnositics; Deccan College of Medical Sciences, Owaisi Hospital and Research Centre; Kanchanbagh, Hyderabad-500058 Hyderabad ANDHRA PRADESH
9848034860
aejazhabeeb@hotmail.com
Arijit De
Dispur Hospitals Pvt Ltd
Department of Gastroenterology, Institute of Digestive and Liver Disease; Dispur Hospitals Pvt Ltd, Ganeshguri, Dispur, Guwahati 781006 Assam Kamrup ASSAM
9864094739
dr_arijitde@rediffmail.com
Dr Amarender Singh Puri
G B Pant Hospital
Department of Gastroenterology, New Delhi-110002, India
New Delhi DELHI
9718599202
amarender.puri@gmail.com
Nitin Vikas Pai
Grant Medical Foundation
Department of Gastroenterology, Ruby Hall Clinic, 40 Sasoon Road, Pune 411001 Maharashtra India Pune MAHARASHTRA
9822008682
drnitinpai@gmail.com
Haribhakti Sanjiv Pravinbhai
Kaizen Hospital institute of Gastroentrology & Research Center
Department of Gastroenterology , 132 feet Ring Road, Helmet Cicle, Memnagar, Ahmedabad - 380052 Gujarat India Ahmadabad GUJARAT
9824440044
sharibhakti@gmail.com
B Vishwanath Tantry
Kasturba Medical College Hospital
Department of Gastroenterology, Manipal Centre for Clinical Research, 7th Floor, Kasturba Medical College Hospital, Attavar, Mangalore, Karnataka 575001, India Dakshina Kannada KARNATAKA
9845789100
tantrybv@gmail.com
Sobhna Bhatia
King Edward Memorial Hospital and Seth G S Medical College,
Department of Gastroenterology , Parel, Mumbai-400012 Maharashtra, India Mumbai MAHARASHTRA
9869072213
shobna.bhatia@gmail.com
Vardaraj Pralhadarao Gokak
KLEs Dr. Prabhakar Kore Hospital & Medical Research Centre
Department of Gastroenterology,Nehru Nagar, Belagavi- 590010, Karnataka, India
"
Belgaum KARNATAKA
7353691777
vpgokak@gmail.com
Shrikant Vasantrao Mukewar
Midas Multispeciality Hospital Pvt. Ltd,
Department of Gastroenterology , Midas Height, 07 Central Bazar Road, Ramdaspeth, Nagpur-440 010, Maharashtra India Nagpur MAHARASHTRA
7720033280
shrikant_mukewar@yahoo.com
Saumin Prakashbhai Shah
Nirmal Hospital Pvt. Ltd;
Department of Gastroenterology ; Ring Road, Surat-395002, Gujarat, India Surat GUJARAT
9408042224
dr.sauminpshah@gmail.com
Dr B Ramesh Kumar
Osmania General Hospital
Department of Gastroenterology, Osmania General Hospital, Afzalgunj, Hyderabad - 500012, Telangana, India Hyderabad ANDHRA PRADESH
9949043290
bhashyakarla_rk@yahoo.co.in
Philip Abraham
P.D. Hinduja National Hospital and Medical Research Centre,
Department of Gastroenterology , Veer Savarkar Marg, Mahim, Mumbai -400016, Maharashtra, India Mumbai MAHARASHTRA
022244515151
dr_pabraham@hindujahospital.com
Nachiket Avinash Dubale
Poona Hospital & Research Centre
Department of Gastroenterology, 27, Sadashiv Peth, Pune 411030, Maharashtra, India Pune MAHARASHTRA
9021133704
drnachi@yahoo.co.in
Rakesh Tandon
Pushpawati Singhania Research Institute
Department of Gastroenterology , Renal & Digestive Diseases
Sheikh Sarai, Phase-II, New Delhi-110017,
"
New Delhi DELHI
9811081338
drrakeshtandon@hotmail.com
Prashant Vithalrao Rahate
Rahate Surgical Hospital & ICU,
Department of Gastroenterology , Near Telephone Exchange Square, 517, Juni Mangalwari, Central Avenue, , Nagpur-440008, Maharashtra, India Nagpur MAHARASHTRA
9822464068
prashantrahate84@yahoo.com
Mukesh Kalla
S R Kalla Memorial Gastro & General Hospital,
Department of Gastroenterology,78-79, Dhuleshwar Garden, Behind HSBC bank, Sardar Patel Marg, C Scheme Jaipur-302001, Rajasthan, India Jaipur RAJASTHAN
9829050622
drmkalla@rediffmail.com
Vijay Dattatray Borgaonkar
Seth Nandlal Dhoot Hospital,
Department of Gastroenterology ,
A-1, MIDC, Chikalthana, Jalna Road,
Aurangabad-431210, Maharashtra, India"
Aurangabad MAHARASHTRA
9890900460
vijay.ihpba@gmail.com
Sarat Chandra Panigrahi
Sparsh Hospitals & Critical Care (P) Ltd.
Department of Gastroenterology, A/407, Sahid Nagar, Bhubaneswar-751007, Odisha, India Khordha ORISSA
Patients with moderate to severe active Ulcerative Colitis who wre naive to TNF Inhibitors, (1) ICD-10 Condition: K519||Ulcerative colitis, unspecified,
Intervention / Comparator Agent
Type
Name
Details
Intervention
ETROLIZUMAB
IMP, 105 mg given as 0.7 mL of a 150-mg/mL solution will be administered by SC injection Q4W.
Comparator Agent
Placebo
NIL
Inclusion Criteria
Age From
18.00 Year(s)
Age To
80.00 Year(s)
Gender
Both
Details
Able and willing to provide written informed consent
Diagnosis of UC established at least 6 months prior
Moderately to severely active UC as determined by an MCS
Evidence of UC extending a minimum of 20 cm from the anal verge
Naive to treatment with any anti-TNF therapy
ExclusionCriteria
Details
Prior extensive colonic resection, subtotal or total colectomy, or planned surgery for UC
Past or present ileostomy or colostomy
Diagnosis of indeterminate colitis
Any prior treatment with etrolizumab or other anti-integrin agents
Pregnant or lactating
Infection Risk
Abnormal Laboratory Values
Method of Generating Random Sequence
Permuted block randomization, fixed
Method of Concealment
Centralized
Blinding/Masking
Double Blind Double Dummy
Primary Outcome
Outcome
TimePoints
Remission at Week 62 among randomized patients in remission at Week 10
Remission at Week 62 among randomized patients in remission at Week 10
Secondary Outcome
Outcome
TimePoints
Clinical remission at Week 62 among randomized patients in clinical remission at
Week 10
Clinical remission at Week 62
Clinical response at Week 62
Improvement in endoscopic appearance of the mucosa at Week 62
Endoscopic remission at Week 62
Specified above
Target Sample Size
Total Sample Size="350" Sample Size from India="60" 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)?
Brief Summary
Although
there are therapeutic options including anti-TNF agents, a significant
proportion of patients with UC will not experience a durable clinical benefit
with those treatment options. Furthermore, adverse events associated with
anti-TNFs include elevated rates of serious bacterial infection, including TB,
and (more rarely) lymphoma and demyelination (Chang and Lichtenstein 2006). No
currently available therapy achieves sustained remission in more than 10%−30%
of patients with IBD who have chronicdisease
(Hanauer et al. 2002; Sandborn et al. 2005). As noted above, etrolizumab distinguishes
itself from other anti-integrins on the basis of gut selectivity combined with a
potential dual mechanism of action. It binds αEβ7 in addition to α4β7 and so
regulates retention as well as trafficking leukocyte/lymphocyte in the
intestinal mucosa.
In summary, favorable
safety (see Section 1.2) and efficacy data were observed in the Phase II
EUCALYPTUS study and in the OLE study (SPRUCE). Overall, etrolizumab showed
compelling efficacy compared with placebo and there were no clinically significant
safety signals. Additionally, etrolizumab distinguishes itself from vedolizumab
by blocking αEβ7 in addition to α4β7, which is involved in lymphocyte retention
and may contribute to its efficacy and/or safety profile.Etrolizumab is a gut-selective anti-trafficking
agent and does not bind to α4β1 (target for natalizumab), which regulates trafficking
to both mucosal and non-mucosal tissues, including the CNS. Although natalizumab
has been associated with an increased risk of PML, no events of PML to date
have been reported during 2-year PML extensive monitoring in the Phase II
study, EUCALYPTUS, and OLE SPRUCE study.