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

Pfizer

Status and phase: Enrolling; Phase 3

Conditions: Crohn's Disease

Treatments: Drug: Placebo; Drug: Etrasimod

Study type: Interventional

Funder types: Industry

Identifiers

NCT04173273

APD334-202

C5041006 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 1,175 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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:

  1. Oral corticosteroids (eg, prednisone or its equivalent, budesonide)
  2. Immunosuppressants (eg, azathioprine [AZA], 6 mercaptopurine [6-MP], or methotrexate [MTX])
  3. Tumor necrosis factor alpha (TNFα) antagonists (eg, infliximab, adalimumab, certolizumab pegol, or biosimilars)
  4. Integrin receptor antagonist (eg, vedolizumab)
  5. 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

1,175 participants in 3 patient groups, including a placebo group

Etrasimod Dose A

Experimental group

Treatment:

Drug: Etrasimod

Drug: Etrasimod

Etrasimod Dose B

Experimental group

Treatment:

Drug: Etrasimod

Drug: Etrasimod

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo