An investigational study to assess the safety and effectiveness of a new investgational drug in people with moderate and severe Crohn's disease

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2015-001249-10-CZ
• Date of registration: 14/08/2015
• 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 moderate and severe Crohn's disease
• Scientific title: A Phase 2, Double-blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Safety and Efficacy of GS-5745 in Subjects with Moderately to Severely Active Crohn’s Disease
• Date of first enrolment: 01/10/2015
• Target sample size: 175
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-001249-10
• 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: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Canada, Czech Republic, Germany, Hungary, Iceland, New Zealand, South Africa, Spain, United Kingdom, United States

Contacts

• Name: Medical Monitor
• Affiliation: Gilead Sciences Inc

• Name: Medical Monitor
• Affiliation: Gilead Sciences Inc

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 non-pregnant, non-lactating females, ages 18 to 75 years, inclusive based on the date of the screening visit
3) Females of childbearing potential must have a negative pregnancy test at screening and baseline.
4) Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception as described in the protocol
5) Documented diagnosis of Crohn’s disease with a minimum disease duration of 6 months with involvement of the ileum and/or colon at a minimum
6) Moderately to severely active Crohn’s disease as defined by a CDAI total score between
220-450 (inclusive) AND with protocol defined parameters
7) Within the previous 5 years, demonstrated an inadequate clinical response, loss of response to, or intolerance of at least one of the following agents as defined in the protocol:
a) Corticosteroids
b) Immunomodulators
c) TNFa Antagonists
d) Vedolizumab
8) Protocol defined Laboratory parameters
9) May be receiving the following drugs:
a) Oral 5-aminosalicylate (5-ASA) compounds provided the dose has been stable for at least 2 weeks prior to screening
b) Oral corticosteroid therapy (prednisone at a stable dose = 30 mg/day or budesonide at a
dose of = 9 mg/day) provided the dose has been stable for 2 weeks prior to screening
c) Antidiarrheals for chronic diarrhea
d) Azathioprine or 6-MP or methotrexate provided the dose has been stable for 4 weeks
prior to screening
e) Antibiotics for the treatment of Crohn’s Disease (e.g., metronidazole, ciprofloxicin)
provided the dose has been stable for the 2 weeks prior to screening or is consistent with
subject’s standard low-dose regimen
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 155
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
1) Pregnant or lactating females
2) Males and females of reproductive potential who are unwilling to use an effective
contraception during the study or complete abstinence from intercourse from the date of
screening to study completion and up to 90 days post last dose of the study drug
3) 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
4) Male subjects unwilling to refrain from sperm donation for at least 90 days after the last dose
of study drug
5) Known hypersensitivity to GS-5745
6) Evidence of abscess at screening
7) Extensive colonic resection (subtotal or total colectomy) or history of > 2 small bowel resections
8) Ileostomy, colostomy, or symptomatic stenosis of the intestine
9) Current use of oral corticosteroids at a dose equivalent to > 30 mg/day of prednisone
10) Ulcerative colitis or indeterminate colitis
11) Short bowel syndrome
12) Stool sample positive for Clostridium difficile (C. difficile) toxin, E. coli, Salmonella,
Shigella, Campylobacter or Yersinia
13) Treatment with infliximab, adalimumab, natalizumab, golimumab, vedolizumab,
certolizumab, or any other monoclonal antibody within 4 weeks of screening.
14) Clinically significant active infection
15) History or evidence of colonic mucosal dysplasia
16) Chronic medical or psychiatric problem that may interfere with subject’s ability to comply with study procedures
17) Co-infection with chronic HIV, hepatitis B, or hepatitis C
18) Active tuberculosis (TB) infection or history of latent tuberculosis that has not been treated
19) Alcohol or drug abuse (in the opinion of the Investigator) that would interfere with
compliance
20) History of malignancy within the last 5 years except for subjects who have been treated or resected for non-melanoma skin cancer or cervical carcinoma in situ
21) Any other investigational therapy or investigational biologics use within 4 weeks of
screening
22) Any chronic medical condition (including, but not limited to, cardiac or pulmonary disease) that, in the opinion of the Investigator, would make the subject unsuitable for the study or would prevent compliance with the study protocol


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

Health Condition(s) or Problem(s) studied

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

Crohn's Disease
MedDRA version: 19.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders

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)

Primary end point(s): The co-primary efficacy endpoints will include:
1) The proportion of subjects achieving clinical response (PRO2 score = 8) at Week 8
2) The proportion of subjects achieving endoscopic response (= 50% reduction from baseline SES-CD) at Week 8

Main Objective: The co-primary objectives of this study are:
• To evaluate the efficacy of an 8 week induction regimen of GS-5745 to induce a clinical response, defined as a PRO2 score = 8 at Week 8
• To evaluate the efficacy of an 8 week induction regimen of GS-5745 to induce an endoscopic response, defined as a reduction in the SES-CD of = 50% from baseline at Week 8

Secondary Objective: The secondary objectives of this study are:
• To evaluate the efficacy of an induction regimen of GS-5745 on clinical remission of Crohn’s Disease, defined as CDAI = 150 at Week 8 (CDAI remission)
• To evaluate the efficacy of an induction regimen of GS-5745 placebo on mucosal healing, defined as an SES-CD presence and size of ulcer subscore = 0 at Week 8
• To determine the safety profile of GS-5745
• To assess the PK characteristics of GS-5745

Timepoint(s) of evaluation of this end point: 8 weeks

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 8 weeks

Safety and PK throughout the duration of the study

Secondary end point(s): Secondary efficacy endpoints are:
The proportion of subjects achieving CDAI remission (CDAI = 150) at Week 8
The proportion of subjects achieving mucosal healing (SES-CD ulcer subscore = 0) at Week 8

Secondary ID(s)

NCT02405442

2015-001249-10-HU

GS-US-395-1663

Source(s) of Monetary Support

Gilead Sciences Inc