A study evaluating the efficacy and safety of Etrasimod in the treatment of patients with moderately to severely active Ulcerative Colitis
- Conditions
- lcerative ColitisTherapeutic area: Diseases [C] - Digestive System Diseases [C06]MedDRA version: 20.1Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 100000004856MedDRA version: 20.1Level: LLTClassification code 10045366Term: Ulcerative colitis, unspecifiedSystem Organ Class: 100000004856
- Registration Number
- EUCTR2018-003986-33-BE
- 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, 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 12m 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 12m 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. Anti-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 = 2w 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
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 disorder, or multiple myeloma
21. Hyperse
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method