A study evaluating the efficacy and safety of Etrasimod in the treatment of patients with moderately to severely active Ulcerative Colitis

Phase 1

• Conditions: lcerative Colitis; MedDRA version: 20.1Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 100000004856; MedDRA version: 20.1Level: LLTClassification code 10045366Term: Ulcerative colitis, unspecifiedSystem Organ Class: 100000004856; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2018-003986-33-SK
• Lead Sponsor: Arena Pharmaceuticals Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-05-02
• Last Update Posted: 21 March 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 330

Inclusion Criteria

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 and to be compliant with the schedule of protocol assessments
3. Diagnosed with UC = 3 months prior to screening confirmed by endoscopic and histologic evidence.
4. Active UC confirmed by endoscopy with = 10 cm rectal involvement.
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 within 12 months before baseline. Subjects without a surveillance colonoscopy within the prior 12 months will have a colonoscopy at screening (ie, in place of screening proctosigmoidoscopy).
7. Demonstrated an inadequate response to, loss of response to, or intolerance to at least 1 of the following therapies:
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. Anti-interleukin 12/23 antibodies (eg, ustekinumab)
d. JAK inhibitors (eg, tofacitinib)
Concomitant treatments:
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
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 total bilirubin level = 1.5 × the upper limit of normal (ULN) range and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels = 2.0 × ULN. Subjects with an isolated total bilirubin and normal AST and ALT diagnosed with Gilbert’s syndrome may participate
11. Adequate renal function defined by an estimated glomerular filtration rate = 30 mL/min/1.73 m2 by the Chronic Kidney Disease Epidemiology Collaboration equation at screening
12. 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
- Permanent sterilization procedure, such as hysterectomy, bilateral salpingectomy, or bilateral oophorectomy
b. Non-pregnant female of childbearing potential must agree to using a highly effective contraception method during treatment and for 30 days following treatme

Exclusion Criteria

1. Severe extensive colitis as evidenced by:
Physician judgement that the subject is likely to require hospitalization for medical care or surgical intervention for UC within 12w following randomization
Current evidence of fulminant colitis, toxic megacolon or recent history (last 6m) 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 IV steroids within 12w of screening
5. Positive assay or stool culture for pathogens or positive test for Clostridioides difficile toxin at screening
6. Pregnancy, lactation, or a +ve serum ß hCG at 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 = 6m prior to or during the Screening Period
• History or presence of :
second or third-degree AV block, sick sinus syndrome, or periods of asystole for > 3 seconds without a functional pacemaker;recurrent symptomatic bradycardia or recurrent cardiogenic syncope
• Screening and or W0/Day 1 prerandomization vital signs with a heart rate (HR) < 50 bpm OR systolic blood pressure (BP) < 90 mm Hg OR diastolic BP < 55 mm Hg.
• Screening and or W0/Day 1 prerandomization ECG with PR interval > 200 ms or Fridericia’s corrected QT interval = 450 ms in men or = 470 ms in women
Start, stop, change or planned change in dosage of any anti-arrhythmic drugs (Class I to IV) = 1w b4 screening or within 1w b4 or after 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 = 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 hep C infection or test positive for hep C virus (HCV) at screening as defined by positive for hep 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 within the last 5y
20. History of lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative diso

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified