A study evaluating the efficacy and safety of Etrasimod in the treatment of patients with moderately to severely active Crohn's Disease

• Register: EUCTR
• Last refreshed on: 16 September 2024
• Main ID: EUCTR2020-004775-40-BG
• Date of registration: 13/07/2021
• Prospective Registration: Yes
• Primary sponsor: Arena Pharmaceuticals Inc.
• Public title: A study evaluating the efficacy and safety of Etrasimod in the treatment of patients with moderately to severely active Crohn's Disease
• Scientific 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 - CULTIVATE
• Date of first enrolment: 29/09/2021
• Target sample size: 1265
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-004775-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: seameless Ph2/3 If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belarus, Belgium, Bosnia and Herzegovina, Brazil, Bulgaria, Canada, Chile, Colombia, Croatia, Czech Republic, 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, Peru, Philippines, Poland, Portugal, Puerto Rico, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Sweden, Switzerland, Türkiye, Ukraine, United Kingdom, United States

Contacts

• Name: Craig Fisco
• Affiliation: Arena Pharmaceuticals, Inc.

• Name: Craig Fisco
• Affiliation: Arena Pharmaceuticals, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
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 unweighted average daily loose/watery stool frequency (SF) 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
- Oral corticosteroids (eg, prednisone [or its equivalent] or budesonide)
- Immunosuppressants (eg, azathioprine, 6-mercaptopurine, or methotrexate)
- Tumor necrosis factor alpha (TNFa) 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 must meet either a or b of the following criteria and males must meet criterion c to qualify for the study:
a. A female who is not of childbearing potential must meet 1 of the following:
- Postmenopausal, defined as no menses for 12 months without an alternative medical cause and confirmed by follicle-stimulating hormone (FSH) within postmenopausal range according to local standards
- Permanent sterilization procedure, such as hysterectomy, bilateral salpingectomy, or bilateral oophorectomy
b. A female who is of childbearing potential must agree to using a highly effective contraception method during treatment and for 4 weeks following treatment that can achieve a failure rate of less than 1% per year when used consistently and correctly.
The following are considered highly effective birth control methods:
- Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, which may be oral, intravaginal, or transdermal
- Progestogen-only hormonal contraception associated with inhibition of ovulation, which may be oral, injected, or implanted
- Intrauterine device (IUD)
- Intrauterine hormone-releasing system (IUS)
- Bilateral tubal occlusion
- Vasectomized partner, provided that partner is the sole sexual partner of the FOCBP trial participant and that the vasectomized partner has received medical assessment of the surgical success
- Sexual abstinence (complete sexual abstinence defined as refraining from heterosexual intercourse for the entire period of risk associated with study drug). The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the subject. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not acceptable
c. A male must agree to using condoms during treatment and for 4 weeks following treatment
SS3-M, SS4-E: Females and males must continue to meet contraception criterion described above
Are the trial subjects under 18?
Exclusion criteria:
Key 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)
- 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 (ie, have > 3 small bowel resections) 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. Subjects who have undergone previous colonic resection or ileocolectomy must have > 25 cm of colon remaining
- Have an ileostomy or a colostomy
- Have a serious infection requiring intravenous antibiotic(s)/medication(s) = 4 weeks prior to randomization
- 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 HIV, HBV, or active HCV
- Lactating female who is breastfeeding


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Crohn's Disease
MedDRA version: 20.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders

Intervention(s)

Product Name: Etrasimod
Product Code: APD334
Pharmaceutical Form: Tablet
INN or Proposed INN: etrasimod L-arginine
CAS Number: 1206123-97-8
Current Sponsor code: APD334 L-arginine;PF-07915503-94 (L-arginine salt)
Other descriptive name: AR401959 L-arginine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: Etrasimod
Product Code: APD334
Pharmaceutical Form: Tablet
INN or Proposed INN: etrasimod L-arginine
CAS Number: 1206123-97-8
Current Sponsor code: APD334 L-arginine; PF-07915503-94 (L-arginine salt)
Other descriptive name: AR401959 L-arginine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 14 (SSA-P2, SS1-P2b, SS2-I)
Week 52 (SS3-M)
Week 66 (SSA-P2)

Main Objective: SSA
•The safety, tolerability, and efficacy of 2 doses of etrasimod as
induction therapy in subjects with moderately to severely active Crohn's
disease (CD)
SS1 - Cohort 1
• The dose-response relationship of 2 doses of etrasimod vs placebo as
induction therapy
• An oral etrasimod dose, based on efficacy and safety for continued
development
SS1 Cohort 2
• To prevent break in the enrollment of the study between completion of
enrollment for
Cohort 1 and the selection of etrasimod dose for SS2
•The primary objective of Substudy 2 by pooling the data from the
selected etrasimod dose group and placebo group with Substudy 2 data
in the primary analysis for SS2
SS2
• The efficacy of the selected etrasimod dose vs placebo as induction
therapy in subjects with moderately to severely active CD
SS3
• The efficacy of etrasimod vs placebo as maintenance therapy in
subjects
SS4
• The long-term safety and tolerability of etrasimod in subjects with
moderately to severely active CD

Primary end point(s): SSA-P2
Portion of subjects with endoscopic response
SS1-P2b
Proportion of subjects with endoscopic response at Week 14
SS2-I
Proportion of subjects with endoscopic response at Week 14
Proportion of subjects with clinical remission CDAI at Week 14
SS3-M
Proportion of subjects with clinical remission CDAI at Week 52
Proportion of subjects with endoscopic response at Week 52

Secondary Objective: SSA
long-term safety, tolerability & efficacy of etrasimod in subjects with
moderately to severely active CD
PK effects of etrasimod as induction & maintenance therapy in subjects
with moderately to severely active CD
SS1
Safety, tolerability & efficacy of etrasimod in subjects with moderately to
severely active CD
SS2
safety & tolerability of selected etrasimod Ph3 dose vs placebo as
induction therapy in subjects with moderately to severely active CD
SS3
efficacy of etrasimod on sustained clinical remission & endoscopic
response, endoscopic remission & corticosteroid-free clinical remission
in subjects with moderately to severely active CD characterize safety &
tolerability of etrasimod as maintenance therapy in subjects with
moderately to severely active CD
SS4
Long-Term efficacy of etrasimod in subjects with moderately to severely
active CD

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 14 (SS1-P2b, SS2-I)
Week 52 (SS3-M)
Week 66 (SSA-P2)
Week 274 (SS4-E)

Secondary end point(s): 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 (Ctrough,ss) at selected timepoints
Change and percentage change from baseline in ALC
Change and percent change from baseline in FCP concentration
Change and percent change from baseline in CRP
SS1-P2b:
Proportion of subjects with clinical remission CDAI at Week 14
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
SS3-M
• Proportion of subjects with clinical remission CDAI at Week 52 among subjects in clinical remission CDAI at SS3-M baseline (defined as Week 14 or EI-Week 6 Visit)
• Proportion of subjects with endoscopic response at Week 52 among subjects in endoscopic response at SS3-M baseline
• Proportion of subjects with corticosteroid-free clinical remission CDAI at Week 52 among subjects receiving corticosteroids at SS3-M baseline
• Proportion of subjects with endoscopic remission at Week 52
• Proportion of subjects with clinical remission PRO2 at Week 52
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

Secondary ID(s)

2020-004775-40-NL

APD334-202EU

Source(s) of Monetary Support

Arena Pharmaceuticals Inc.

Ethics review

Status: Approved
Approval date: 17/09/2021
Contact: