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

Crohn Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05033340
• Other study ID #: 00012021
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: September 1, 2021
• Est. completion date: August 31, 2025

Study information

• Verified date: August 2021
• Source: Theodor Bilharz Research Institute
• Contact: samia H El-Shishtawy, ASS. PROF
• Phone: 01003661563
• Email: crc.tbri[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

This is a seamless Phase 2/3, multicenter, randomized, double-blind, study that comprises 5 substudies designed to evaluate the efficacy, safety, and tolerability of etrasimod as therapy in subjects with moderately to severely active CD who are refractory or intolerant to at least 1 of the current therapies for CD (ie, corticosteroids, immunosuppressants, or biologics). Subjects who are refractory or intolerant to corticosteroids and/or immunosuppressants may be either previously exposed to or naïve to biologics. Randomized subjects will remain on stable doses of 5-aminosalicyclic acid compounds, low-dose oral corticosteroids, and/or anti-diarrheal medications as background therapy for CD; however, corticosteroid tapering may be required in subjects who continue treatment beyond the Induction Period. The 5 substudies are presented in the study schematic and described below.

Substudy A - Phase 2 (SSA-P2): A Phase 2, randomized, double-blind, substudy to assess the safety, tolerability, and efficacy of oral etrasimod therapy in subjects with moderate to severe CD that supports the selection of an induction and maintenance dose(s) for Phase 3. Substudy 1 - Phase 2 (SS1-P2b): 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 (SS2-I): A Phase 3 randomized, double-blind, placebo-controlled substudy to evaluate etrasimod as induction therapy. Substudy 3 - Maintenance (SS3-M): A Phase 3 randomized, double-blind, placebo-controlled substudy to evaluate etrasimod as maintenance therapy. Substudy 4 - Long-Term Extension (SS4-E): A long-term extension (LTE) substudy for subjects who complete at least 52 weeks of treatment.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 5
• Est. completion date: August 31, 2025
• Est. primary completion date: August 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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, TNFa 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

Related Conditions & MeSH terms

• Crohn Disease

Intervention

Drug:
• Etrasimod
Study drug will be provided in induction-sealed, high-density polyethylene bottles with child-resistant screw caps.
• Placebo
Study placebo will be provided in induction-sealed, high-density polyethylene bottles with child-resistant screw caps.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Samia Hassan El-Shishtawy	Arena Pharmaceuticals

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Key efficacy assessments	Key efficacy assessments in this study include changes in CDAI and SES-CD (centrally read). Efficacy will also be assessed by unweighted daily AP (kg) and loose/watery SF symptom scores (electronic diary), Patient Reported Outcome 2 (PRO2), histopathology (centrally read), biomarkers (eg, C-reactive protein, fecal calprotectin, total lymphocyte count, Endoscopic Healing Index), assessment of extraintestinal manifestations of CD, and other subject-reported outcome measures (Inflammatory Bowel Disease Questionnaire, Crohn's Disease Patient-Reported Outcomes Signs and Symptoms, AP numerical rating scale, Medical Outcomes Study 36 Item Short Form Health Survey, EuroQoL - 5 Dimensions 5-level version, Work Productivity and Activity Impairment Questionnaire - Crohn's disease, Patient Global Impression of Change, Functional Assessment of Chronic Illness Therapy - Fatigue, and CD-related hospitalizations and surgeries).	424 week
Secondary	Endpoint definitions:	Endpoint definitions: Endoscopic response: endoscopic remission or = 50% decrease from baseline in SES-CD; Endoscopic remission: SES-CD = 4 and at least 2-point reduction from baseline with no sub-score > 1; Clinical response CDAI: Clinical remission CDAI or = 100-point decrease from baseline in CDAI; Clinical remission CDAI: CDAI < 150; Clinical response PRO2: Clinical remission PRO2 or = 8-point decrease from baseline in PRO2; Clinical response CDAI-70: Clinical remission CDAI or = 70-point decrease from baseline in CDAI; Clinical remission PRO2: PRO2 < 8; Corticosteroid-free remission: CDAI < 150 without receiving corticosteroids for = 4 weeks prior to Week 52 (for subjects receiving corticosteroids at baseline)	52 week