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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Arena Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

9 Jul 2021 → 9 Jun 2025

Decision date (initial)

2024-09-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Arena Pharmaceuticals, Inc., a wholly owned subsidiary of Pfizer Inc.

External identifiers

EU CT number

2024-513569-38-00

EudraCT number

2020-004775-40

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic, Others, Pharmacogenomic, Pharmacoeconomic, Pharmacodynamic

Substudy A (SSA): •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 (SS1):•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, based on efficacy and safety, for continued development. Please refer to protocol section 2 for more objectives.

Secondary objectives 5

1. Substudy A: •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 CD.
2. Substudy 1: • To evaluate the 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
3. Substudy 2: • 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
4. Substudy 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
5. Substudy 4: • To evaluate the long-term efficacy of etrasimod in subjects with moderately to severely active CD

Conditions and MedDRA coding

Crohn's Disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Subjects 18 to 80 years of age, inclusive, at the time of consent
2. Ability to provide written informed consent and to be compliant with the schedules of protocol assessments
3. 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 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.
4. Have moderately to severely active CD at Screening, defined as: Crohn’s Disease Activity Index (CDAI) score ≥ 220 and ≤ 450, AND  Unweighted average worst daily abdominal pain (AP) score ≥ 2 (using a 4-point scale; ie, 0 [none] to 3 [severe]) OR unweighted average daily loose/watery stool frequency (SF) (Bristol Stool Form Scale [BSFS] type 6 or 7) score ≥ 4, AND Simple Endoscopic Score in Crohn’s disease (SES-CD) of ≥ 6 or SES-CD ≥ 4 for subjects with isolated ileal disease
5. Demonstrated inadequate response, loss of response to, or intolerance to ≥ 1 of the following therapies for the treatment of CD (refer to Appendix 9, refer to Appendix 11 for Israel specific criteria): - Oral corticosteroids (eg, prednisone [or its equivalent] or budesonide) - Immunosuppressants (eg, azathioprine, 6-mercaptopurine, or methotrexate) - Tumor necrosis factor alpha (TNFα) antagonists (eg, infliximab, adalimumab, certolizumab pegol, or biosimilars) - Integrin receptor antagonist (eg, vedolizumab) - Interleukin-12/-23 antagonist (eg, ustekinumab)
6. Females of childbearing potential must be nonpregnant
7. Females of childbearing potential and males must agree to use contraception (refer to Section 4, Inclusion Criterion 7 for SSA-P2, SS1-P2b, or SS2-I; Inclusion Criterion 6 for SS3-M; and Inclusion Criterion 4 for SS4-E)

Exclusion criteria 9

1. 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)
2. 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
3. Have functional or post-operative short-bowel syndrome or any associated complications that may require surgery or interfere with efficacy assessments
4. Had surgical treatment for intra-abdominal abscesses ≤ 8 weeks prior to randomization or surgical treatment for perianal abscesses ≤ 4 weeks prior to randomization
5. Had intestinal resection ≤ 24 weeks prior to randomization or other intra-abdominal surgeries ≤ 12 weeks prior to randomization. Subjects who have undergone previous colonic resection or ileocolectomy must have > 25 cm of colon remaining
6. Have an ileostomy or a colostomy
7. Have a serious infection requiring intravenous antibiotic(s)/medication(s) ≤ 4 weeks prior to randomization
8. Have primary or secondary immunodeficiency syndromes, history of organ transplant, history of an opportunistic infection, history of disseminated herpes simplex or herpes zoster, have or test positive for human immunodeficiency virus, hepatitis B virus, or active hepatitis C virus
9. Lactating female who is breastfeeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. SSA-P2:Proportion of subjects with endoscopic response
2. SS1-P2b:Proportion of subjects with endoscopic response at Week 14
3. SS2-I: • Proportion of subjects with endoscopic response at Week 14. • Proportion of subjects with clinical remission CDAI at Week 14
4. SS3-M: • Proportion of subjects with clinical remission CDAI at Week 52 • Proportion of subjects with endoscopic response at Week 52

Secondary endpoints 5

1. SSA-P2:• Proportion of subjects with clinical remission CDAI • Change from baseline in SES-CD score • Change from baseline in CDAI score. •Etrasimod plasma concentrations at 4 hours postdose and at steady-state trough concentrations at selected timepoints.• Change and percentage change from baseline in ALC.
2. SS1-P2b:• Proportion of subjects with clinical remission CDAI at Week 14 • Proportion of subjects with clinical remission by PRO2 at Week 14
3. SS2-I:• Proportion of subjects with clinical remission PRO2 at Week 14 • Proportion of subjects with clinical response CDAI at Week 14 • Proportion of subjects with endoscopic response and clinical remission CDAI at Week 14 • Proportion of subjects with endoscopic remission at Week 14 •
4. SS3-M: • Proportion of subjects with clinical remission CDAI at Week 52 among subjects in clinical remission CDAI at SS3-M baseline • Proportion of subjects with endoscopic response at Week 52 among subjects in endoscopic response at SS3-M baseline
5. SS4-E:• Proportion of subjects with clinical remission CDAI by visit up to the end of treatment • Proportion of subjects with clinical remission PRO2 by visit up to the end of treatment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Arena Pharmaceuticals Inc.

Sponsor organisation

Arena Pharmaceuticals Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Arena Pharmaceuticals Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Arena Pharmaceuticals Inc.

Contact name

Clinical Medical Lead

Third parties 18

Locations

15 EU/EEA countries · 74 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 212 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications