E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011401 |
E.1.2 | Term | Crohn's disease |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
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 |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacokinetic (PK) Substudy
An optional PK substudy will be performed in a subset of subjects (approximately 30 subjects enrolled in the Blinded Induction Treatment) who provide a separate consent. In the PK substudy, one additional plasma PK sample will be collected on 3 (± 1) and 5 (± 1) days after the Week 0 injection.
Magnetic Resonance Enterography (MRE) Substudy
An optional MRE substudy will be performed in a subset of subjects (approximately 50 subjects enrolled in the Blinded Induction Treatment from select sites) who agree to participate and provide a separate consent. Sites will be chosen based on prior experience with MRE.
The aim of this substudy is to assess the efficacy of GS-5745 as determined by MRE. In the MRE substudy, subjects will undergo imaging prior to dosing at Week 0 and again at Week 8. |
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E.3 | Principal 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) TNFα 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 |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | 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 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
8 weeks
Safety and PK throughout the duration of the study |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
New Zealand |
South Africa |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |