The Efficacy and Safety of Oral Etrasimod as Therapy for Moderately to Severely Active Crohn's Disease

• Status: Not yet recruiting
• Trial end date: 2025-08-31
• Target enrollment: 0
• Participant gender: All

Summary

Objectives:

Primary Objectives Substudy A - Phase 2

• To evaluate the safety, tolerability, and efficacy of 2 doses of etrasimod as induction therapy in subjects with moderately to severely active Crohn's disease (CD) Substudy 1 - Phase 2b

• To evaluate the dose-response relationship of 2 doses of etrasimod versus placebo as induction therapy in subjects with moderately to severely active CD

• To select an oral etrasimod dose(s), based on efficacy and safety, for continued development Substudy 2 - Induction (Phase 3)

• To evaluate the efficacy of the selected etrasimod dose versus placebo as induction therapy in subjects with moderately to severely active CD Substudy 3 - Maintenance (Phase 3)

• To evaluate the efficacy of etrasimod versus placebo as maintenance therapy in subjects with moderately to severely active CD Substudy 4 - Long-Term Extension

• To evaluate the long-term safety and tolerability of etrasimod in subjects with moderately to severely active CD Secondary Objectives Substudy A - Phase 2

• To evaluate the long-term safety, tolerability, and efficacy of etrasimod in subjects with moderately to severely active CD

• To evaluate the pharmacokinetic (PK) and pharmacodynamic effects of etrasimod as induction and maintenance therapy, including changes in lymphocytes, C-reactive protein (CRP), and fecal calprotectin (FCP) in subjects with moderately to severely active CDSubstudy 1 - Phase 2b

• To evaluate the long-term safety, tolerability, and efficacy of etrasimod in subjects with moderately to severely active CD

• To provide a subset of the target study population, etrasimod responders, to be evaluated in Substudy 3 - Maintenance Substudy 2 - Induction (Phase 3)

• To evaluate the safety and tolerability of the selected etrasimod Phase 3 dose (3 mg or 2 mg) versus placebo as induction therapy in subjects with moderately to severely active CD

• To provide a subset of the target study population, etrasimod responders, to be evaluated in Substudy 3 - Maintenance Substudy 3 - Maintenance (Phase 3)

• To evaluate the efficacy of etrasimod on sustained clinical remission and endoscopic response, endoscopic remission, and corticosteroid-free clinical remission in subjects with moderately to severely active CD

• To characterize the safety and tolerability of etrasimod as maintenance therapy in subjects with moderately to severely active CD Substudy 4 - Long-Term Extension

• To evaluate the long-term efficacy of etrasimod in subjects with moderately to severely active CD

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Samia Hassan El-Shishtawy
• Collaborator: Arena Pharmaceuticals

Criteria

Inclusion Criteria:

• Subjects 18 to 80 years of age, inclusive, at the time of consent

• Ability to provide written informed consent and to be compliant with the schedules of protocol assessments

• Have CD for ≥ 3 months prior to randomization, involving the ileum and/or colon, at a minimum; diagnosis may be confirmed at any time in the past by endoscopy and/or histopathology. The screening endoscopy and histopathology reports may serve as source documents for subjects who do not have diagnostic endoscopy reports in their medical chart

• Have moderately to severely active CD at Screening, defined as:

• CDAI score ≥ 220 and ≤ 450

• Unweighted average worst daily AP (kg) score ≥ 2 (using a 4-point scale; ie, 0 [none] to 3 [severe]) OR unweighted average daily loose (kg)/watery SF (Bristol Stool Form Scale [BSFS] type 6 or 7) score ≥ 4

• SES-CD of ≥ 6 or SES-CD ≥ 4 for subjects with isolated ileal disease, Demonstrated inadequate 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] or budesonide Immunosuppressants (eg, AZA, 6-mercaptopurine [6-MP], or MTX)

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, refer to Appendix 9)

• Have stopped, started, or changed the dosage of oral 5-ASA compounds ≤ 2 weeks prior to randomization or do not intend to maintain the same dose during the study

• 3Have stopped, started, or changed the dosage of oral corticosteroids (prednisone ≤ 20 mg/day or its equivalent, budesonide ≤ 9 mg/day) ≤ 2 weeks prior to randomization

• Have a confirmed ALC < 800 cells/mm3 (< 0.8 × 109 cells/L) at Screening or confirmed absolute neutrophil count < 1000 cells/mm3 (< 1.0 × 109 cells/L) at Screening

• Have confirmed aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 × upper limit of normal (ULN) and total bilirubin > 1.5 × ULN (unless consistent with a history of Gilbert's Syndrome) at Screening