PDF of Trial CTRI Website URL -

Transcription

1 Clinical Trial Details (PDF Generation Date :- Sat, 09 Mar :40:46 GMT) CTRI Number Last Modified On 03/03/2017 Post Graduate Thesis Type of Trial Type of Study Study Design Public Title of Study Scientific Title of Study CTRI/2016/09/ [Registered on: 23/09/2016] - Trial Registered Prospectively Interventional Drug Other (Specify) Randomized, Parallel Group, Placebo Controlled Trial A clinical investigational study to check effects of GS-5745 (study molecule) in patients with Active Ulcerative Colitis A Combined Phase 2/3, Double-Blind, Randomized, Placebo-Controlled, Induction and Maintenance Study Evaluating the Safety and Efficacy of GS-5745 in Subjects with Moderately to Severely Active Ulcerative Colitis Secondary IDs if Any Secondary ID Identifier Details of Principal Investigator or overall Trial Coordinator (multi-center study) GS-US , Amendment 2 dated 27 Oct 2015 Designation Affiliation Protocol Number Details of Principal Investigator Details Contact Person (Scientific Query) Details Contact Person (Public Query) Phone Fax Designation Affiliation Details Contact Person (Scientific Query) Dr Vikram Vora Medical Monitor Klinera Corporation Phone Fax Designation Affiliation Klinera Corporation, 401, Hill View Industrial Estate, LBS Marg, Ghatkopar West, Mumbai Klinera Corporation, 401, Hill View Industrial Estate, LBS Marg, Ghatkopar West, Mumbai Mumbai vvora@klinera.com Details Contact Person (Public Query) Mr Pravin Moily Clinical Project Manager Klinera Corporation Klinera Corporation, 401, Hill View Industrial Estate, LBS Marg, Ghatkopar West, Mumbai Klinera Corporation, 401, Hill View Industrial Estate, LBS Marg, Ghatkopar West, Mumbai page 1 / 9

2 Source of Monetary or Material Support Primary Sponsor Details of Secondary Sponsor Countries of Recruitment Mumbai Phone Fax Source of Monetary or Material Support > Gilead Sciences Inc 333 Lakeside Drive Foster City, CA Type of Sponsor Klinera Corporation Hill View Industrial Estate Ghatkopar West Mumbai List of Countries Austria Belarus Belgium Brazil Bulgaria Canada Croatia Czech Republic France Germany Hong Kong Hungary Iceland Ireland Israel Italy Japan Latvia Netherlands New Zealand Poland Romania Russian Federation Serbia Slovakia South Africa Spain Switzerland Taiwan Ukraine Primary Sponsor Details Gilead Sciences Inc Lakeside Drive Foster City CA USA 333 Lakeside Drive Foster City, CA USA Pharmaceutical industry-global 401, Hill View Industrial Estate Ghatkopar West, Mumbai page 2 / 9

3 Sites of Study United Kingdom of Principal Investigator Dr Vineet Ahuja Dr Kartikeya Parmar DrAjit Sood Dr B D Goswami Dr Rahul Shah of Site Site Phone/Fax/ All Institute of Medical Sciences B J Medical College and Civil Hospitals Dayanand Medical College & Hospital Gastroenterology, Room : 3093, 3rd floor, Teaching block, Delhi , New Delhi DELHI Gastroenterology, Asarwa, Ahmedabad , Gujarat Ahmadabad GUJARAT Gastroenterology, Civil Lines, Ludhiana , Punjab, Ludhiana PUNJAB Dispur Hospitals Pvt Ltd Institute of digestive and liver disease, Dept of Gastroenterology, ground floor,ganeshguri, Guwahati: , Assam, Goalpara ASSAM Global Hospital and Baldota Institute of Digestive Sciences Gastroenterology 3rd Floor,Hospital A venue, Dr. E. Borges Road, Opp. Shirodkar High School, Parel , Mumbai. Mumbai Dr Lata Prasad Global Hospitals Gastroenterology / 1 to 4, Lakdi ka Pul, Hyderabad , Telangana Hyderabad ANDHRA PRADESH Dr Gopal Krishna Dhali Institute of Post Graduate Medical Education and Research, School of Digestive & Liver Diseases vins_ahuja@hotmail.co m drkartik@gmail.com ajitsood10@gmail.com bhabadev@rediffmail.c om rahulhshah@hotmail.co m lataprasad@yahoo.com Ronald Ross building, Gastroenterology, 4th gkdhali@yahoo.co.in floor, Room - 17, 244 AJC bose road,kolkata , West Bengal Kolkata WEST BENGAL page 3 / 9

4 Dr Atul Shah Kaizen Hospital Gastroenterology, Situated at 132 Feet Ring Road, Helmet Circle, Memnagar, Ahemdabad , Gujarat Ahmadabad GUJARAT Dr Vaibhav Ganjewar Dr Tantry Vishwanath DrShrikant Mukewar Dr Ramesh Roop Rai Dr Deepak Kumar Gupta Dr Rajiv Mehta Kamalnayan Bajaj Hospital Kasturba Medical College Hospital Midas Multispeciality Hospital Pvt Ltd S.R. Kalla Memorial Gastro & General Hospital Seth GS Medical College and KEM hospital Surat Institute of Digestive Sciences Gastroenterology, Gut -43, Bajaj Marg, Beed Bypass Road, Satara Parisar, Aurangabad , Maharashtra Aurangabad Gastroenterology Ambedkar Circle, Mangalore, Karnataka Chikmagalur KARNATAKA 4th floor, Gastroenterology, 7 - Central Bazar Road, Ramdaspeth, Nagpur , Maharashtra, Nagpur Gastroenterology, 78, Dhuleshwar Garden, Behind HSBC Bank, Sardar Patel Marg, C-Scheme, Jaipur, Rajasthan , Jaipur RAJASTHAN Gastroenterology, 9th floor, Parel, Mumbai , Maharashtra Mumbai Dept Gastroenterology, 2nd floor,vijay Nagar Gate -3, Besides Nirman Bhavan, Opp Gandhi College, Majura Gate, Surat , Gujarat Surat GUJARAT atulshah@kaizenhospit al.com vaibhav@ganjewar.com tantrybv@gmail.com shrikant_mukewar@ya hoo.com rameshroop@gmail.co m dkgt@rediffmail.com rmgastro@yahoo.com Dr V G Mohan Prasad VGM Hospital page 4 / 9

5 Details of Ethics Committee Gastroenterology, First floor, 2100, Trichy Road, Rajalakshmi Mills Stop,Coimbatore , Tamil Nadu,. Coimbatore TAMIL NADU of Committee Approval Status Date of Approval Is Independent Ethics Committee? Drug Trial Ethics Committee,Ludhiana,Punjab- Dr.Ajit Sood Ethics Committee Kamalnayan Bajaj Hospital-Dr Vaibhav Ganjewar Ethics Committee, Dispur Hospitals Pvt. Ltd- Dr. B D Goswami Institute of Ethics Committee, All Institute of Medical Sciences- Dr. Vineet Ahuja Institutional Ethics Committee (IEC) II. Seth G SMedical College and KEM hospital,mumbai, ; Dr. Deepak K Gupta Institutional Ethics Committee, B. J. Medical College & Civil Hospital- Dr. Kartikeya Parmar Institutional Ethics Committee, Global Hospitals- Dr. Lata Prasad Institutional Ethics Committee- Dr. Rahul Shah IPGME&R Research Oversight Committee- Dr. G K Dhali Kaizen Hospital Ethics Committee- Dr. Atul Shah Manipal University Ethics Committee-Dr.Tantry Vishwanath Midas Multispeciality Hospital Institutional Ethics Committee- Dr. Shrikant Mukewar Date Specified Date Specified Approved 05/04/2016 Approved 03/08/2016 Date Specified Date Specified Approved 08/04/2016 Date Specified Approved 28/07/2016 Approved 10/08/2016 Approved 10/03/2016 Approved 30/04/2016 S. R. Kalla Memorial Approved 10/03/2016 page 5 / 9

6 Regulatory Clearance Status from DCGI Health Condition / Problems Studied Intervention / Comparator Agent Inclusion Criteria Ethical committee for Human research- Dr. Ramesh Roop Rai Surat Institute of Digestive Sciences, Dr. Rajiv Mehta VGM Hospital Institutional Ethics- Dr. V G Mohan Prasad Status Approved 30/07/2016 Approved 21/03/2016 Date Approved/Obtained 23/08/2016 Health Type Patients Condition Moderately to Severely Active Ulcerative Colitis Patients Type Details Intervention Treatment Group 1 :150mg GS5745,subcutaneous injection weekly. Treatment Group 2: 150 mg GS-5745 subcutaneous injection alternating with matching placebo weekly, for a total of 4 active GS-5745 doses (GS-5745 every 2 weeks) Open label maintenance phase: GS mg weekly Extended Treatment phase: GS mg weekly. Total Duration of Therapy 208 weeks. Comparator Agent Placebo subcutaneous injection weekly Age From Age To Gender Details Year(s) Year(s) Both Inclusion Criteria 1)Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures 2)Males or non-pregnant, non-lactating females, ages 18 to 75 years, inclusive based on the date of the screening visit 3)Documented diagnosis of UC of at least 6 months AND with a minimum disease extent of 15 cm from the anal verge 4)A surveillance colonoscopy is required at screening in subjects with a history of ulcerative colitis for 8 or more years, if one was not performed in the prior 24 months 5)Moderately to severely active UC as determined by a centrally read endoscopy score? 2, a rectal bleeding score? 1, a stool frequency score? 1 and PGA of 2 or 3as determined by the Mayo clinical scoring system with endoscopy occurring within 14 days to first dose of study drug 6) Demonstrated at any time over the prior 5 years, an inadequate clinical response or loss of response to, or intolerance of at least one of the following agents: Corticosteroids Active disease despite a history of at least one 4-week induction regimen of a dose equivalent to prednisone 30 mg daily for 2 weeks or IV for 1 week, OR Two failed attempts to taper steroids below a dose equivalent of 10 mg daily prednisone, OR History of steroid intolerance including, but not limited to, Cushing s syndrome, osteopenia/osteoporosis, hyperglycemia, insomnia, serious infections, depression, allergic reactions, mood disturbances, or any other condition that contributed to discontinuation of the agent page 6 / 9

7 Immunomodulators Active disease despite a history of at least a 12 week regimen of oral azathioprine (? 1.5 mg/kg or mg/kg in the EU) or 6-MP (? 0.75 mg/kg or mg/kg in the EU), OR History of intolerance to at least one immunomodulator including, but not limited to, serious infections, hepatotoxicity, cytopenia, pancreatitis,tpmt genetic mutation, allergic reactions, or any other condition that contributed to discontinuation of the agent TNF? Antagonists Active disease despite a history of at least one 4-8 week induction regimen of infliximab/golimumab (or at least 14 weeks in the EU, adalimumab, certolizumab or biosimilar, OR Recurrence of symptoms during maintenance therapy with the above agents, OR History of intolerance to any TNF? agents including, but not limited to, serious infections, hepatotoxicity, heart failure, allergic reactions, or any other condition that contributed to discontinuation of the agent Vedolizumab Active disease despite a history of at least a 10 week induction regimen, OR Recurrence of symptoms during maintenance therapy with the above agents, OR History of intolerance of vedolizumab including, but not limited to, serious infections, hepatotoxicity, cytopenia, allergic reactions, or any other condition that contributed to discontinuation of the agent 7)May be receiving the following drugs: Oral 5-ASA compounds provided the dose has been stable for at least 2 weeks prior to screening, and/or Oral corticosteroid therapy (prednisone at a stable dose? 30 mg/day or equivalent) provided the dose has been stable for 2 weeks prior to screening, and/or Azathioprine or 6-MP provided the dose has been stable for 8 weeks prior to screening 8) Females of childbearing potential must have a negative pregnancy test at screening and baseline. 9)Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception Exclusion Criteria Details Exclusion Criteria 1)Known hypersensitivity to the study investigational medicinal products or components 2)Exhibit severe UC as defined by the following criteria:? 6 bloody stools daily AND one or more of the following: Body temperature > F ( or 38 C) Pulse > 90 beats/minute 3)Laboratory parameters: Liver panel (AST, ALT, total bilirubin, alkaline phosphatase) > 2 times the ULN Serum creatinine > 2 times the ULN Hemoglobin Absolute neutrophil count (ANC) Platelets 4) Use of rectal formulations of 5-ASA compounds or corticosteroids 2 weeks prior to screening 5) Crohn s disease or indeterminate colitis 6) History of colectomy, partial colectomy, or dysplasia on biopsy page 7 / 9

8 7) History of colonic or small bowel stoma 8) Stool sample positive for clostridium difficile (C. difficile) toxin, Escherichia coli, Salmonella, Shigella, Campylobacter or Yersinia 9) Stool sample positive for ova and parasites test (O&P) unless approved by the medical monitor 10) Treatment with infliximab, adalimumab, natalizumab, golimumab, vedolizumab, certolizumab, or TNF? biosimilar agent 4 weeks prior to screening (and last dose must be at least 8 weeks prior to randomization) 11) Treatment with non-biologic therapies (eg, cyclosporine, thalidomide) other than those permitted in Section 5.4 at least 4 weeks prior to screening 12) Other clinically significant active infection 13) Chronic medical or psychiatric problem that may interfere with subject s ability to comply with study procedures 14) Co-infection with chronic HIV, hepatitis B or hepatitis C 15) Active tuberculosis or history of latent tuberculosis that has not been treated Method of Generating Random Sequence Method of Concealment Blinding/Masking Computer generated randomization Case Record Numbers Participant and Investigator Blinded Primary Outcome Outcome Timepoints cohort 1:Proportion of subjects achieving EBS clinical remission at Week 8,The primary outcome for Cohort 2 is: Proportion of subjects achieving EBS clinical remission at Week 52 week 8,week 52 Secondary Outcome Outcome Timepoints The secondary outcome for Cohort 1 are: Proportion of subjects achieving MCS remission at Week 8 Proportion of subjects achieving MCS response at Week 8 Proportion of subjects achieving sustained EBS clinical remission at Week 52 (defined as achieving EBS clinical remission at both Week 8 and Week 52) The secondary efficacy endpoints for Cohort 2 are: Proportion of subjects achieving MCS remission at Week 52 Proportion of subjects achieving corticosteroid-free EBS clinical remission at Week 52 Proportion of subjects achieving endoscopic remission (endoscopic subscore of 0) at Week 52 Target Sample Size Total Sample Size=1600 Sample Size from =200 Phase of Trial Phase 2/ Phase 3 Date of First Enrollment () Date of First Enrollment (Global) Estimated Duration of Trial 01/11/ /09/2015 Years=4 Months=0 Days=0 page 8 / 9

9 Powered by TCPDF ( Recruitment Status of Trial (Global) Recruitment Status of Trial () Publication Details Brief Summary Other (Terminated) Other (Terminated) not applicable This study is a Combined Phase 2/3, Double-Blind, Randomized, Placebo-Controlled, Induction and Maintenance Study Evaluating the Safety and Efficacy of GS mg/kg. The protocol encompasses an Induction Study (Cohort 1), a Maintenance Study (Cohort 2), and an Extended Treatment Phase. The Induction Study consists of two parts: Part A (the first 150 subjects) and Part B (up to 510 additional subjects). Results of a futility analysis of safety and endoscopic efficacy data from Part A will be reviewed by the Data Monitoring Committee (DMC). Continuation of Part B is contingent on the DMC s recommendation. Once the optimal induction treatment is determined from Cohort 1, enrollment into the Maintenance Study (Cohort 2) will be initiated with up to 940 new subjects. All subjects that complete 52 weeks of treatment including flexible sigmoidoscopy/colonoscopy will have the option to continue receiving open label GS-5745 for an additional 3 years in the Extended Treatment Phase. page 9 / 9