|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Medical condition in easily understood language
|Crohn's Disease a form of inflammatory bowel disease.
|Diseases [C] - Digestive System Diseases [C06]
|E.1.2 Medical condition or disease under investigation
|System Organ Class
|10017947 - Gastrointestinal disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|•To evaluate the dose-response relationship of 2 doses of etrasimod versus placebo as induction therapy in subjects with moderately to severely active Crohn’s disease (CD).
To select an oral etrasimod dose, based on efficacy and safety, for continued development.
|Secondary objectives of the trial
|•To evaluate the long-term safety, tolerability, and efficacy of etrasimod in subjects with moderately to severely active Crohn’s disease (CD).
|Trial contains a sub-study
|Principal inclusion criteria
|1. Men or women 18 to 80 years of age,
2. Ability to provide written informed consent and to be compliant with the schedule of protocol assessments
3. Diagnosed with CD ≥ 3 months
4.Have moderately to severely active CD at Screening
5.Demonstrated inadequate response, loss of response to, or intolerance to ≥ 1 of the following therapies for the treatment of CD:
a.Oral corticosteroids (eg, prednisone or its equivalent, budesonide)
b.Immunosuppressants (eg, azathioprine [AZA], 6 mercaptopurine [6 MP], or methotrexate [MTX])
c.Tumor necrosis factor alpha (TNFα) antagonists (eg, infliximab, adalimumab, certolizumab pegol, or biosimilars)
d.Integrin receptor antagonist (eg, vedolizumab)
e.Interleukin 12/ 23 antagonist (eg, ustekinumab)
6.Females of childbearing potential must be nonpregnant
7.Females of childbearing potential and males must use contraception
|Principal exclusion criteria
|- History of inadequate response (ie, primary non response) to agents from ≥ 2 classes of biologics marketed for the treatment of CD (ie, TNFα antagonists, interleukin 12/ 23 antagonist, and integrin receptor antagonist).
- Have ulcerative colitis, indeterminate colitis, microscopic colitis, ischemic colitis, radiation colitis, diverticular disease associated colitis, toxic megacolon, or active infectious colitis or test positive for Clostridium difficile toxin at Screening.
- Have functional or post operative short bowel syndrome or any associated complications that may require surgery or interfere with efficacy assessments
- Had surgical treatment for intra abdominal abscesses ≤ 8 weeks prior to randomization or surgical treatment for perianal abscesses ≤ 4 weeks prior to randomization.
- Had intestinal resection ≤ 24 weeks prior to randomization or other intra abdominal surgeries ≤ 12 weeks prior to randomization.
- Have an ileostomy or a colostomy.
- Have a serious infection requiring IV antibiotics/medication(s) ≤ 4 weeks prior to randomization.
- Have primary or secondary immunodeficiency syndromes, opportunistic infection, or infection with HIV, HBV, HCV or tuberculosis (active or latent):.
- Have a clinically relevant cardiovascular condition or receiving treatments that may effect cardiovascular function
- Have active retinopathy or macular oedema.
- Have forced expiratory volume at 1 second or forced vital capacity < 70% of predicted values at Screening.
- Lactating female who is breastfeeding.
- Any acute illnesses or medical conditions including cognitive impairment and alcohol/drug abuse/dependence, or signs/symptoms suspicious for a serious disease that, in the Investigator's opinion, could put the subject at increased risk for safety event(s) or interfere with protocol-specified procedures or adherence with study treatment.
|E.5 End points
|Primary end point(s)
|Proportion of subjects who achieve endoscopic response at Week 14
|Timepoint(s) of evaluation of this end point
|Secondary end point(s)
|• Proportion of subjects who achieve clinical remission APSF at Week 14
• Proportion of subjects who achieve CDAI < 150 by visit up to Week 14
• Proportion of subjects who achieve clinical response CDAI by visit up to Week 14
• Proportion of subjects who achieve clinical response APSF by visit up to Week 14
• Proportion of subjects who achieve clinical response CDAI-70 by visit up to Week 14
• Proportion of subjects who achieve clinical response APSF-30 by visit up to Week 14
• Change from baseline in CDAI score by visit up to Week 14
• Change from baseline in SES-CD at Week 14
• Proportion of subjects with clinical response by PRO2 at Week 14
• Proportion of subjects with endoscopic response and clinical remission by PRO2 at Week 14
• Change and percentage change from baseline in absolute lymphocyte count by visit up to Week 14
• Change and percentage change from baseline in FCP concentration at Weeks 2, 4, 6, 10, and 14
• Change and percentage change from baseline in CRP concentration at Weeks 2, 4, 6, 10, and 14
• Proportion of subjects who achieve endoscopic remission at Week 14
endpoints for the induction period will be assessed at scheduled visits up to Week 66.
|Timepoint(s) of evaluation of this end point
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Other scope of the trial description
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Korea, Republic of
|Moldova, Republic of
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days