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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04173273
Recruitment Status : Recruiting
First Posted : November 21, 2019
Last Update Posted : September 7, 2022
Sponsor:
Information provided by (Responsible Party):
Arena Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE November 20, 2019
First Posted Date  ICMJE November 21, 2019
Last Update Posted Date September 7, 2022
Actual Study Start Date  ICMJE February 12, 2020
Estimated Primary Completion Date October 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 3, 2020)
  • Number and Severity of Adverse Events [Substudy A] [ Time Frame: Up to approximately 70 weeks ]
    Safety will be assessed by monitoring adverse events and clinically relevant changes in vital signs and clinical laboratory results.
  • Proportion of Participants With Endoscopic Response [Substudy 1] [ Time Frame: Week 14 ]
  • Proportion of Participants With Endoscopic Response [Substudy 2] [ Time Frame: Week 14 ]
  • Proportion of Participants With Clinical Remission Crohn's Disease Activity Index (CDAI) [Substudy 2] [ Time Frame: Week 14 ]
  • Proportion of Participants With Clinical Remission CDAI [Substudy 3] [ Time Frame: Week 52 ]
  • Proportion of Participants With Endoscopic Response [Substudy 3] [ Time Frame: Week 52 ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 20, 2019)
Proportion of Participants Who Achieve Endoscopic Response [ Time Frame: Week 14 ]
Endoscopic response is defined as ≥ 50% decrease from baseline in simple endoscopic score in Crohn's disease (SES-CD)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 3, 2020)
  • Proportion of Participants With Endoscopic Response [Substudy A] [ Time Frame: Weeks 14 and 66 ]
  • Proportion of Participants With Clinical Remission CDAI [Substudy A] [ Time Frame: Up to Week 66 ]
  • Change From Baseline in Simple Endoscopic Score in Crohn's Disease (SES-CD) Score [Substudy A] [ Time Frame: Baseline to Week 66 ]
  • Change From Baseline in CDAI Score [Substudy A] [ Time Frame: Baseline to Week 66 ]
  • Proportion of Participants With Clinical Remission CDAI [Substudy 1] [ Time Frame: Week 14 ]
  • Proportion of Participants With Clinical Remission Patient Reported Outcome 2 (PRO2) [Substudy 2] [ Time Frame: Week 14 ]
  • Proportion of Participants With Clinical Response CDAI [Substudy 2] [ Time Frame: Week 14 ]
  • Proportion of Participants With Endoscopic Response and Clinical Remission CDAI [Substudy 2] [ Time Frame: Week 14 ]
  • Proportion of Participants With Endoscopic Remission [Substudy 2] [ Time Frame: Week 14 ]
  • Proportion of Participants With Clinical Remission CDAI Among Participants In Clinical Remission CDAI at Substudy 3 Baseline [Substudy 3] [ Time Frame: Week 52 ]
  • Proportion of Participants With Endoscopic Response Among Participants in Endoscopic Response at Substudy 3 Baseline [Substudy 3] [ Time Frame: Week 52 ]
  • Proportion of Participants With Corticosteroid-Free Clinical Remission CDAI Among Participants Receiving Corticosteroids at Substudy 3 Baseline [Substudy 3] [ Time Frame: Week 52 ]
  • Proportion of Participants With Endoscopic Remission [Substudy 3] [ Time Frame: Week 52 ]
  • Proportion of Participants With Clinical Remission PRO2 [Substudy 3] [ Time Frame: Week 52 ]
  • Proportion of Participants With Clinical Remission CDAI by Visit up to the End Of Treatment [Substudy 4] [ Time Frame: Up to Week 208 ]
  • Proportion of Participants With Clinical Remission PRO2 by Visit up to the End Of Treatment [Substudy 4] [ Time Frame: Up to Week 208 ]
  • Number and Severity of Adverse Events [ Time Frame: Up to approximately 24 weeks for Substudy 1 and 2; 42 weeks for Substudy 3; and 212 weeks for Substudy 4 ]
    Safety will be assessed by monitoring adverse events and clinically relevant changes in vital signs and clinical laboratory results.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2019)
  • Proportion of Participants Who Achieve Clinical Remission Worst Daily Abdominal Pain With Loose/Watery Stool Frequency Scores (APSF) [ Time Frame: Week 14 ]
    Clinical remission APSF is defined as unweighted average worst daily abdominal pain (AP) score ≤ 1 (using a 4-point scale; ie, 0 [none] to 3 [severe]) and unweighted average daily loose/watery (Bristol Stool Form Scale [BSFS] type 6 or 7) SF score ≤ 3.
  • Number and Severity of Adverse Events [ Time Frame: Up to Week 66 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Evaluating the Efficacy and Safety of Oral Etrasimod in the Treatment of Adult Participants With Moderately to Severely Active Crohn's Disease
Official Title  ICMJE 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
Brief Summary 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 28-Day 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

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 A is currently closed for enrollment.

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 1 is currently enrolling participants.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Crohn's Disease
Intervention  ICMJE
  • Drug: Etrasimod
    Dose A taken by mouth, once daily.
    Other Name: APD334
  • Drug: Etrasimod
    Dose B taken by mouth, once daily.
    Other Name: APD334
  • Drug: Placebo
    Etrasimod matching placebo tablet taken by mouth, once daily.
Study Arms  ICMJE
  • Experimental: Etrasimod Dose A
    Intervention: Drug: Etrasimod
  • Experimental: Etrasimod Dose B
    Intervention: Drug: Etrasimod
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 3, 2020)
1265
Original Estimated Enrollment  ICMJE
 (submitted: November 20, 2019)
225
Estimated Study Completion Date  ICMJE December 2029
Estimated Primary Completion Date October 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Arena CT.gov Administrator +1 855-218-9153 ct.gov@arenapharm.com
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belarus,   Belgium,   Bosnia and Herzegovina,   Bulgaria,   Canada,   Chile,   Colombia,   Croatia,   Czechia,   Denmark,   Egypt,   France,   Georgia,   Germany,   Greece,   Hungary,   India,   Ireland,   Israel,   Italy,   Japan,   Korea, Republic of,   Latvia,   Lebanon,   Lithuania,   Malaysia,   Mexico,   Moldova, Republic of,   Netherlands,   Norway,   Philippines,   Poland,   Portugal,   Puerto Rico,   Romania,   Russian Federation,   Serbia,   Slovakia,   South Africa,   Spain,   Switzerland,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04173273
Other Study ID Numbers  ICMJE APD334-202
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Arena Pharmaceuticals
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Arena Pharmaceuticals
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Arena CT.gov Administrator Arena Pharmaceuticals
PRS Account Arena Pharmaceuticals
Verification Date September 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP