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-FR
- 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, women and adolescents 16 to 80 years of age
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. Enrollment of
subjects < 18 years should be conducted only if acceptable according to local laws and regulations.
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. Inclusion of subjects with proctitis only at baseline will be capped at 15% of the total subjects enrolled.
c. A male must agree to use condoms during treatment and for 4 weeks following treatment.
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 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. Corticosteroids
b. 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. 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 aminosalicylates 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. Vital signs at screening and prerandomization taken in the sitting position: heart rate = 50 bpm, systolic blood pressure (BP) = 90 mm Hg, and diastolic BP = 55 mm Hg
10. Screening and prerandomization 12 lead electrocardiogram (ECG) showing no clinically significant abnormalities with a PR interval = 200 ms, Fridericia’s corrected QT interval (QTcF) < 450 ms (men) or QTcF < 470 ms (women)
11. Adequate hematological function
12. Adequate hepatic function. Subjects with an
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 Crohn’s disease or indeterminate colitis or the presence or history of a fistula consistent with Crohn’s disease
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 (a single dose of IV steroids given is acceptable)
5. Positive assay or stool culture for pathogens or positive test for Clostridium difficile toxin at screening
6. Pregnancy, lactation, or a positive serum ß hCG measured during screening
7. Clinically relevant hematologic, hepatic, neurological, pulmonary, ophthalmological, endocrine, metabolic, psychiatric or other major systemic disease making implementation of the protocol or interpretation of the study difficult or would put the subject at risk
8. Recent history (within 6 months of the Screening) of cardiovascular disease, including myocardial infarction or unstable angina, stroke/ transient ischemic attack, decompensated heart failure (requiring inpatient treatment), or New York Heart Association Class III/IV heart failure
9. Any history of the following, unless treated with an implanted pacemaker or an implanted cardioverter-defibrillator with pacing:
• History or presence of symptomatic bradycardia
• History of sick sinus syndrome or neurocardiogenic syncope
• Second or third degree AV block
• Periods of asystole > 3 seconds
10. Forced expiratory volume at 1 second (FEV1) or forced vital capacity (FVC) < 70% of predicted values and FEV1/FVC ratio < 0.70 at screening
11. Uncontrolled diabetes at screening, or subjects with diabetes with significant comorbid conditions such as retinopathy
12. History of macular edema or retinopathy
13. Current or past history of active tuberculosis (TB), history of untreated latent TB infection, or test positive for latent TB infection at screening.
14. Known active bacterial, viral, fungal, mycobacterial infection, or other infection or any major episode of infection that required hospitalization or treatment with IV antibiotics within 30 days of screening or during screening or oral antibiotics within 14 days prior to screening. Fungal infection of nail beds is allowed
15. Have HIV/acquired immune deficiency syndrome or test positive for HIV antibodies at screening
16. Have acute or chronic hepatitis B infection or test positive for hepatitis B virus (HBV) at screening
17. Have current hepatitis C infection or test positive for hepatitis C virus (HCV) at screening
18. History of an opportunistic infection (eg, pneumocystis carinii, cryptococcal meningitis, progressive multifocal leukoencephalopathy) or serious bacterial, viral, or fungal infections (eg, disseminated herpes simplex, disseminated herpes zoster) requiring IV medication(s) = 3 weeks prior to randomization
19. History of or currently active primary or secondary immunodeficiency
20. History of cancer within the last 5 years, including solid tumors and hematological malignancies (except basal cell and in situ squamous cell carcinomas of the skin that have
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