An investigational study to assess the safety and effectiveness of a new investgational drug in people with moderately to severely active Ulcerative Colitis

• Register: EUCTR
• Last refreshed on: 17 October 2016
• Main ID: EUCTR2014-005217-24-SK
• Date of registration: 07/10/2015
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc
• Public title: An investigational study to assess the safety and effectiveness of a new investgational drug in people with moderately to severely active Ulcerative Colitis
• Scientific title: 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
• Date of first enrolment: 12/11/2015
• Target sample size: 1600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-005217-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belarus, Belgium, Brazil, Bulgaria, Canada, Colombia, Croatia, Czech Republic, Germany, Hong Kong, Hungary, Iceland, India, Iran, Islamic Republic of, Ireland, Israel, Korea, Republic of, Latvia, Malaysia, Mexico, Moldova, Republic of, Netherlands, New Zealand, Philippines, Romania, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States, Vietnam

Contacts

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences International Ltd.

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences International Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must meet all of the following inclusion criteria to be eligible for participation in this study.
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 females (non-pregnant, non-lactating), 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 (depending on current treatment recommendations/guidelines):
• Corticosteroids
• Immunomodulators
• TNFa Antagonists
• Vedolizumab
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 or methotrexate provided the dose has been stable for 8 weeks prior to screening
8) Females of childbearing potential (as defined in the protocol) 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 as defined in the protocol
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 160
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1440

Exclusion criteria:
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
1) Known hypersensitivity to the study investigational medicinal products or components
2) Exhibit severe UC as definedin the protocol:
3) Laboratory parameters:
• Liver panel (AST, ALT, total bilirubin, alkaline phosphatase) > 2 times the ULN
• Serum creatinine > 2 times the ULN
• Hemoglobin < 8 g/dL (both males and females)
• Absolute neutrophil count (ANC) < 1.5 × 109/L (1,500 mm3)
• Platelets < 100 × 109/L
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
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 positive for ova and parasites test (O&P) unless approved by the medical monitor
10) Treatment with infliximab, adalimumab, natalizumab, golimumab, vedolizumab, certolizumab, or TNFa 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
16) History of malignancy in the last 5 years except for subjects who have been successfully treated for non-melanoma skin cancer or cervical carcinoma in situ
17) Any other investigational therapy or investigational biologics use 4 weeks prior to screening (and at least 8 weeks prior to randomization)
18) Any chronic medical condition (including, but not limited to, cardiac or pulmonary disease, alcohol or drug abuse) that, in the opinion of the Investigator, would make the subject unsuitable for the study or would prevent compliance with the study protocol
19) Females who may wish to become pregnant and/or plan to undergo egg donation or egg harvesting for the purpose of current or future fertilization during the course of the study and up to 30 days of the last dose of the study drug
20) Male subjects unwilling to refrain from sperm donation 90 days after the last dose of study drug
21) Treatment with tacrolimus within 4 weeks prior to screening
22) Treatment with apheresis therapy within 6 months prior to screening


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Ulcerative Colitis

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Code: GS-5745
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: GS-5745
Current Sponsor code: GS-5745
Other descriptive name: GS-5745
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 8 or Week 52

Primary end point(s): The primary efficacy endpoint for Cohort 1 is:
• Proportion of subjects achieving EBS clinical remission at Week 8

The primary efficacy endpoint for Cohort 2 is:
• Proportion of subjects achieving EBS clinical remission at Week 52

Secondary Objective: To evaluate the efficacy of GS-5745
• induction treatment on achieving MCS defined remission and response at Wk 8 (Cohort 1)
• induction and maintenance treatment on sustained EBS clinical remission at Wk 52 (EBS clinical remission at both Wk 8 and 52) (Cohort 1)
• induction treatment on endoscopic response (subscore 0 or 1) and remission (subscore of 0) at Wk 8; mucosal healing (Geboes histologic scoring) at Wk 8 (Cohort 1)
• maintenance treatment on MCS remission at Wk 52 (Cohort 2); on achieving corticosteroid-free; EBS clinical remission at Week 52 (Cohort 2); endoscopic remission (subscore of 0) at Wk 52 (Cohort 2); mucosal healing as determined by the Geboes histologic scoring system at Wk 52 (Cohort 2)
•To evaluate the efficacy of GS-5745 To assess the PK characteristics of GS-5745 (Cohorts 1 and 2)
•To evaluate the efficacy of GS-5745 To evaluate the immunogenicity of GS-5745 treatment as measured by the emergence of anti-drug-antibodies (ADA) (Cohorts 1 and 2)

Main Objective: • To evaluate the efficacy of GS-5745 to induce EBS clinical remission at Week 8 (Cohort 1)
• To evaluate the efficacy of GS-5745 to maintain EBS clinical remission at Week 52 (Cohort 2)
• To evaluate the safety and tolerability of GS-5745

Secondary Outcome(s)

Secondary end point(s): The secondary efficacy endpoints 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)
• Proportion of subjects achieving endoscopic remission (endoscopic subscore of 0) at Week 8
• Proportion of subjects achieving endoscopic response (endoscopic subscore 0 or 1) at Week 8
• Proportion of subjects achieving mucosal healing as determined by the Geboes histologic scoring system at Week 8

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
• Proportion of subjects achieving mucosal healing as determined by the Geboes histologic scoring system at Week 52

Timepoint(s) of evaluation of this end point: Week 8 and/or Week 52

Secondary ID(s)

GS-US-326-1100

2014-005217-24-HU

Source(s) of Monetary Support

Gilead Sciences Inc