Health Condition 1: null- Moderately to Severely Active Ulcerative Colitis Patients
Conditions
Interventions
Intervention1: 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 activ
Sponsors
Gilead Sciences Inc Lakeside Drive Foster City CA USA
Klinera Corporation India Hill View Industrial Estate Ghatkopar West Mumbai
Eligibility
Inclusion criteria
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, Cushingâ??s syndrome, osteopenia/osteoporosis, hyperglycemia, insomnia, serious infections, depression, allergic reactions, mood disturbances, or any other condition that contributed to discontinuation of the agent •Immunomodulators Active disease despite a history of at least a 12 week regimen of oral azathioprine (>= 1.5 mg/kg or 2-2.5 mg/kg in the EU) or 6-MP (>= 0.75 mg/kg or 1-1.5 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 •TNFα 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 TNFα 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 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
Exclusion criteria
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 > 100.3 °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) Crohnâ??s disease or indeterminate colitis 6) History of colectomy, partial colectomy, or dysplasia on biopsy 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 TNFα 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 subjectâ??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
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| 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) Timepoint: 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 | — |
Primary
| Measure | Time frame |
|---|---|
| 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 Timepoint: week 8 ,week 52 | — |
Countries
Austria, Belarus, Belgium, Brazil, Bulgaria, Canada, Croatia, Czech Republic, France, Germany, Hong Kong, Hungary, Iceland, India, Ireland, Israel, Italy, Japan, Latvia, Netherlands, New Zealand, Poland, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Switzerland, Taiwan, Ukraine, United Kingdom
Contacts
Public ContactMr Pravin Moily
Klinera Corporation India
Outcome results
None listed