A study evaluating the efficacy and safety of Etrasimod in the treatment of patients with moderately to severely active Ulcerative Colitis
- Conditions
- lcerative ColitisMedDRA version: 20.1Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 100000004856MedDRA version: 20.1Level: LLTClassification code 10045366Term: Ulcerative colitis, unspecifiedSystem Organ Class: 100000004856Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2018-003986-33-HR
- Lead Sponsor
- Arena Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 330
1. Men or women 16 to 80 years of age, inclusive, at the time of assent/consent. Enrollment of subjects < 18 years should be conducted only if acceptable according to local laws and regulations
2. Ability to provide written informed consent or assent (parent or legal guardian must provide consent for a subject < 18 years of age who has assented to participate in the study or as required per local regulations) and to be compliant with the schedule of protocol assessments
Disease-specific inclusion criteria:
3. Diagnosed with UC = 3 months prior to screening. The diagnosis of UC must be confirmed by endoscopic and histologic evidence. The endoscopy and histology report should be present in the source documents; however, if not available, the screening endoscopy and histology may serve as such
4. Active UC confirmed by endoscopy with = 10 cm rectal involvement. Subjects with proctitis only at baseline,who meet the other eligibility criteria for inclusion, including the endoscopic and rectal bleeding criteria for moderate to severe disease, will be capped at 15% of the total subjects enrolled.
5. Moderately to severely active UC defined as MMS of 4 to 9, including an ES of = 2 and RB score = 1
6. Received a surveillance colonoscopy (performed according to local standard) within 12 months before baseline to rule out dysplasia in subjects with pancolitis > 8 years duration or subjects with left-sided colitis > 12 years duration. Subjects without a surveillance colonoscopy within the prior 12 months will have a colonoscopy at screening (ie, in place of screening proctosigmoidoscopy). Any adenomatous polyps must be removed according to routine practice prior to their first dose of study treatment.
7. Demonstrated an inadequate response to, loss of response to, or intolerance to at least 1 of the following therapies as defined below:
Conventional therapy
a. Oral 5 aminosalicylic acid (5 ASA) compounds
b. Corticosteroids
c. Thiopurines
Biologic therapy or JAK inhibitor therapy
a. Antitumor necrosis factor alpha (TNFa) antibodies (eg, infliximab, adalimumab, golimumab, or biosimilars)
b. Anti integrin antibodies (eg, vedolizumab)
c.Interleukin 12/23 antibodies (eg, ustekinumab)
d. JAK inhibitors (eg, tofacitinib)
8. Subjects are permitted to be receiving a therapeutic dose of the following drugs:
• Oral 5 ASA compounds provided the dose has been stable for = 2 weeks immediately prior to randomization
• Oral corticosteroid therapy (prednisone at a stable dose = 20 mg/day, budesonide at a stable dose = 9 mg/day, or equivalent steroid) provided the dose has been stable for the 4 weeks immediately prior to the screening endoscopy assessment
• Immunosuppressive agents such as oral azathioprine or 6 mercaptopurine must be discontinued = 2 weeks prior to randomization
• Probiotics (eg, Culturelle®, Saccharomyces boulardii) provided the dose has been stable for the 2 weeks immediately prior to randomization
• Antidiarrheals (eg, loperamide, diphenoxylate with atropine) for control of chronic diarrhea
If oral 5-ASA or corticosteroids have been recently discontinued, they must have been stopped for at least 2 weeks prior to the endoscopy used for the baseline MMS.
9. Adequate hematological function defined by white blood cell count = 3.5 × 109/L with absolute neutrophil count (ANC) = 1.5 × 109/L, lymphocyte count = 0.8 × 109/L, platelet count = 100 × 109/L, and hemoglobin = 8 g/dL
10. Adequate hepatic function defined by a
1. Severe extensive colitis as evidenced by:
Physician judgment that the subject is likely to require hospitalization for medical care or surgical intervention of any kind for UC (eg, colectomy) within 12 weeks of baseline
Current evidence of fulminant colitis, toxic megacolon or recent history (within last 6 months) of toxic megacolon, or bowel perforation
Previous total or partial colectomy
2. Diagnosis of CD or indeterminate colitis or the presence or history of a fistula consistent with CD
3. Diagnosis of microscopic colitis, ischemic colitis, or infectious colitis
4. Hospitalization for exacerbation of UC requiring intravenous (IV) steroids within 12 weeks of screening
5. Positive assay or stool culture for pathogens or positive test for Clostridioides difficile toxin at screening
6. Pregnancy, lactation, or a positive serum ß hCG measured during screening
7. Clinically relevant neurological, endocrine, metabolic, psychiatric, cognitive impairment, alcohol/drug abuse/dependence, or other major systemic disease making implementation of the protocol or interpretation of the study difficult or would put the subject at risk.
8.Have any of the following conditions or receiving treatments that may affect cardiovascular function:
• Myocardial infarction, unstable angina, stroke/transient ischemic attack, decompensated heart failure requiring hospitalization or Class III/IV heart failure within 6 months of the Screening Visit
• History or presence of :
second-degree or third-degree atrioventricular block, sick sinus syndrome without a functional pacemaker, or periods of asystole for > 3 seconds without an implanted cardiac defibrillator;recurrent symptomatic bradycardia or recurrent cardiogenic syncope
prerandomization vital signs with a heart rate (HR) < 50 bpm OR systolic blood pressure (BP) < 90 mm Hg OR diastolic BP < 55 mm Hg.
prerandomization electrocardiogram (ECG) with PR interval > 200 ms or Fridericia’s corrected QT interval (QTcF) = 450 ms in men or = 470 ms in women
Start, stop, or change in dosage of any anti-arrhythmic drugs (Class I to IV) within 1 week of randomization
9. Forced expiratory volume at 1 second (FEV1) or forced vital capacity (FVC) < 70% of predicted values and FEV1/FVC ratio < 0.70 at screening.
10.Uncontrolled diabetes as determined by hemoglobin A1c (HbA1c) > 9% at screening, or subjects with diabetes with significant comorbid conditions such as retinopathy
11. History of macular edema or retinopathy
12.History of active tuberculosis (TB), history of untreated or inadequately treated latent TB infection, active or latent TB infection at screening.
13.A clinically significant active infection (eg, serious and/or atypical) = 28 days prior to randomization, required iv medication = 14 days prior to randomization, or that may worsen if the subject is treated with a drug having immunosuppressant effects
14. Have HIV/acquired immune deficiency syndrome or test positive for HIV antibodies at screening
15. Have acute or chronic hepatitis B infection or test positive for hepatitis B virus (HBV) at screening
16. Have current hepatitis C infection or test positive for hepatitis C virus (HCV) at screening as defined by positive for hepatitis C antibody and detectable HCV RNA
17. History of an opportunistic infection or history of disseminated herpes simplex or disseminated herpes zoster
18. History of or currently active primary or secondary immunodeficiency
19. History of cancer wi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the efficacy of etrasimod when administered for 12 weeks on clinical remission in subjects with moderately to severely active ulcerative colitis (UC).;Secondary Objective: Secondary:<br>The secondary objective is to assess the efficacy of etrasimod when administered for 12 weeks on clinical response, symptomatic response and remission, endoscopic changes, and mucosal healing in subjects with moderately to severely active UC.<br><br>Safety:<br>The safety objective is to assess the safety of etrasimod after daily doses of 2 mg for 12 weeks in subjects with moderately to severely active UC.<br><br>Other:<br>Other objectives include evaluation of etrasimod pharmacokinetics (PK) and the effect of etrasimod on health related subject reported outcomes and biomarkers.;Primary end point(s): The primary efficacy endpoints will evaluate etrasimod versus placebo in:<br>• The proportion of subjects in clinical remission at Week 12;Timepoint(s) of evaluation of this end point: Week 12
- Secondary Outcome Measures
Name Time Method