Crohn's Disease MedDRA version: 20.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Interventions
Sponsors
Arena Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion 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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 •The dose-response relationship of 2 doses of etrasimod vs placebo as induction therapy in subjects with moderately to severely active CD •An oral etrasimod dose, based on efficacy and safety, for continued development along with data generated from SS1 Phase 2b Cohort 1 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;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;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 subj | — |
Secondary
| Measure | Time frame |
|---|---|
| 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;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) | — |
Countries
Argentina, Australia, Austria, Belarus, Belgium, Bosnia and Herzegovina, Brazil, Bulgaria, Canada, Chile, Colombia, Croatia, Czechia, Czech Republic, 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, Thailand, Türkiye, Ukraine, United Kingdom, United States
Contacts
Public ContactCraig Fisco
Arena Pharmaceuticals, Inc.
Outcome results
None listed