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-PT
• Lead Sponsor: Arena Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-10-28
• Study Completion: 2021-12-07
• Last Update Posted: 29 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 354

Inclusion Criteria

1. Men, women and adolescents 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.
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 activeUC 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
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. 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 = 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

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 of any kind for UC
(eg,colectomy) within 12w following randomization
Current evidence of fulminant colitis,toxic megacolon or recent history
(within last 6 m) of toxic megacolon,or bowel perforation
Previous total or partial colectomy
2.Diagnosis of Crohn's disease (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 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 =6 m prior to & during the Screening Period
History or presence of second-degree or third-degree atrioventricular
block,sick sinus syndrome,or periods of asystole for >3seconds without
a funcional pacemaker
History or presence of recurrent symptomatic bradycardia or recurrent
cardiogenic syncope
Screening or W0/D1 prerandomization vital signs with a heart rate
<50bpm OR systolic blood pressure <90mm Hg OR diastolic BP<55mm
Hg & Screening or W0/D1 prerandomization ECG with PR interval
>200ms or Fridericia's corrected QT interval QTcF=450 ms in men or =
470ms in women
Start,stop,change or planned change in dosage of any anti-arrhythmic
drugs (Class I to IV) =1w before screening or within 1w b4 or afterrandomization
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 TB, history of untreated or inadequately treated
latent TB infection, active or latent TB infection at screening
13.A clinically significant active infection =28d prior to randomization
14.Have HIV/acquired immune deficiency syndrome or test positive for
HIV antibodies
15.Have acute or chronic hep B infection or test positive for hep B virus
at screening (detectable HBV DNA, or positive for hep B surface antigen,
or negative for HBsAg & positive for antihepatitis B core antibody in
conjunction with detectable HBV DNA)
16.Have current hep C infection or test positive for hep C virus
17.History of an opportunistic infection or a 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, including solid tumors and
hematological malignancies (except basal cell ∈ situ squamous cell
carcinomas of the skin that have been excised and

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<br>in:<br>• The proportion of subjects achieving clinical remission at Week 12;Timepoint(s) of evaluation of this end point: Week 12

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): The key secondary efficacy endpoints are:<br>• The proportion of subjects achieving endoscopic improvement at Week<br>12<br>• The proportion of subjects achieving symptomatic remission at Week<br>12<br>• The proportion of subjects with mucosal healing at Week 12<br>The other secondary endpoints are:<br>•The proportion of subjects achieving clinical response at Week 12<br>• The proportion of subjects achieving endoscopic normalization at Week<br>12<br>• The proportion of subjects achieving symptomatic remission at Weeks<br>2, 4, 8<br>• The proportion of subjects achieving complete symptomatic remission<br>at each study visit (Weeks 2, 4, 8, 12)<br>• The proportion of subjects achieving noninvasive clinical response at<br>each study visit (Weeks 2, 4, 8, 12)<br>• The proportion of subjects achieving symptomatic response at each<br>study visit (Weeks 2, 4, 8, 12);Timepoint(s) of evaluation of this end point: Weeks 2, 4, 8, and 12 and 2 & 4 weeks follow-up