A Study Evaluating the Efficacy and Safety of Oral Etrasimod in the Treatment of Adult Participants With Moderately to Severely Active Crohn's Disease

Study Overview
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Brief Summary
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This is a Phase 2/3 study that comprises 5 substudies designed to evaluate the efficacy, safety, and tolerability of oral etrasimod as therapy in adult participants with moderately to severely active Crohn's disease (CD) who are refractory or intolerant to at least 1 of the current therapies for CD (ie, corticosteroids, immunosuppressants, or biologics). The overall duration of this study is up to 282 weeks, inclusive of the Screening Period, Treatment Period of up to 274 weeks (Induction, Extension or Maintenance, and Long-term Extension Periods), and the 4-Week Follow-Up Period for safety assessment.

Detailed Description
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This study includes 5 substudies: Substudy A - Phase 2: A Phase 2, randomized, double-blind, substudy to assess the safety, tolerability, and efficacy of oral etrasimod therapy in participants with moderate to severe CD that supports the selection of an induction and maintenance dose(s) for Phase 3. Substudy 1 - Phase 2: A Phase 2b randomized, double-blind, placebo-controlled, dose-ranging induction substudy to evaluate etrasimod as induction therapy and select an induction and maintenance dose(s) for continued evaluation in Phase 3. Substudy 2 - Induction: A Phase 3 randomized, double-blind, placebo-controlled substudy to evaluate etrasimod as induction therapy. Substudy 3 - Maintenance: A Phase 3 randomized, double-blind, placebo-controlled substudy to evaluate etrasimod as maintenance therapy. Participants from Substudy 1 and Substudy 2 will be enrolled in Substudy 3. Substudy 4 - Long-Term Extension: A long-term extension substudy for participants who complete at least 52 weeks of treatment. Participants from Substudy 3 and Substudy A are planned to be enrolled in Substudy 4.

Official Title
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A Multicenter, Randomized, Double-Blind, Parallel-Group Study to Assess the Efficacy and Safety of Oral Etrasimod as Induction and Maintenance Therapy for Moderately to Severely Active Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: Etrasimod
* Drug: Etrasimod
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Eligibility criteria applicable to all substudies: Inclusion Criteria: Men or women 18 to 80 years of age, Ability to provide written informed consent or assent and to be compliant with the schedule of protocol assessments Diagnosed with Crohn's disease (CD) ≥ 3 months Have moderately to severely active CD at Screening Demonstrated inadequate response (ie, primary non-response), loss of response to, or intolerance to ≥ 1 of the following therapies for the treatment of CD: Oral corticosteroids (eg, prednisone or its equivalent, budesonide) Immunosuppressants (eg, azathioprine [AZA], 6 mercaptopurine [6-MP], or methotrexate [MTX]) Tumor necrosis factor alpha (TNFα) antagonists (eg, infliximab, adalimumab, certolizumab pegol, or biosimilars) Integrin receptor antagonist (eg, vedolizumab) Interleukin -12/-23 antagonist (eg, ustekinumab) Females of childbearing potential must be nonpregnant Females of childbearing potential and males must use contraception 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 Clostridioides 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. Inclusion Criteria for Substudy 3: - Participants who entered the Extended Induction Period of Substudy 1 and Substudy 2 must have completed the Extended Induction -Week 6 Visit Inclusion Criteria for Substudy 4: - Participant must have completed the Week 52 Visit of Substudy 3 or the Week 66 Visit of Substudy A

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Etrasimod Dose A<br> | Drug: Etrasimod<br>* Dose A taken by mouth, once daily.<br>* Other names: APD334;|
| Experimental: Etrasimod Dose B<br> | Drug: Etrasimod<br>* Dose B taken by mouth, once daily.<br>* Other names: APD334;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Etrasimod matching placebo tablet taken by mouth, once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants with Endoscopic Response [Substudy A] |  | Weeks 14 and 52 | 
| Proportion of Participants With Endoscopic Response [Substudy 1] |  | Week 14 | 
| Proportion of Participants With Endoscopic Response [Substudy 2] |  | Week 14 | 
| Proportion of Participants With Clinical Remission Crohn's Disease Activity Index (CDAI) [Substudy 2] |  | Week 14 | 
| Proportion of Participants With Clinical Remission CDAI [Substudy 3] |  | Week 52 | 
| Proportion of Participants With Endoscopic Response [Substudy 3] |  | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With Clinical Remission CDAI [Substudy A] |  | Up to Week 66 | 
| Change From Baseline in Simple Endoscopic Score in Crohn's Disease (SES-CD) Score [Substudy A] |  | Baseline to Week 66 | 
| Change From Baseline in CDAI Score [Substudy A] |  | Baseline to Week 66 | 
| Proportion of Participants With Clinical Remission CDAI [Substudy 1] |  | Week 14 | 
| Proportion of Participants with Clinical Remission Patient Reported Outcome 2 (PRO2) [Substudy 1] |  | Week 14 | 
| Proportion of Participants With Clinical Remission Patient Reported Outcome 2 (PRO2) [Substudy 2] |  | Week 14 | 
| Proportion of Participants With Clinical Response CDAI [Substudy 2] |  | Week 14 | 
| Proportion of Participants With Endoscopic Response and Clinical Remission CDAI [Substudy 2] |  | Week 14 | 
| Proportion of Participants With Endoscopic Remission [Substudy 2] |  | Week 14 | 
| Change from baseline in CD-PRO/SS [Substudy 2] |  | Week 14 | 
| Proportion of Participants With Clinical Remission CDAI Among Participants In Clinical Remission CDAI at Substudy 3 Baseline [Substudy 3] |  | Week 52 | 
| Proportion of Participants With Endoscopic Response Among Participants in Endoscopic Response at Substudy 3 Baseline [Substudy 3] |  | Week 52 | 
| Proportion of Participants With Corticosteroid-Free Clinical Remission CDAI Among Participants Receiving Corticosteroids at Substudy 3 Baseline [Substudy 3] |  | Week 52 | 
| Proportion of Participants With Endoscopic Remission [Substudy 3] |  | Week 52 | 
| Proportion of Participants With Clinical Remission PRO2 [Substudy 3] |  | Week 52 | 
| Proportion of Participants with Clinical Response or Endoscopic Response [Substudy 3] |  | Week 52 | 
| Proportion of Participants With Clinical Remission CDAI by Visit up to the End Of Treatment [Substudy 4] |  | Up to Week 208 | 
| Proportion of Participants With Clinical Remission PRO2 by Visit up to the End Of Treatment [Substudy 4] |  | Up to Week 208 | 
| Number and Severity of Adverse Events | Safety will be assessed by monitoring adverse events and clinically relevant changes in vital signs and clinical laboratory results. | Up to approximately 70 weeks for Substudy A,approximately 24 weeks for Substudy 1 and 2; 42 weeks for Substudy 3; and 212 weeks for Substudy 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Etrasimod, Crohn's disease, APD334, Inflammatory bowel disease