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Trial details
Etrasimod Versus Placebo for the Treatment of Moderately to Severely Active Ulcerative Colitis
Current status:
Approved
|
Date registered:
12/11/2020
|
Date last updated:
10/11/2020
Trial version(s)
History: 25/02/2020
Current: 25/02/2020
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Main Information
Primary registry identifying number
LBCTR2020043405
Protocol number
APD334-301
MOH registration number
2020/2/33090
Trial already registered with the MoPH
Study registered at the country of origin
Type of registration
Prospective
Date of registration in national regulatory agency
04/05/2015
Primary sponsor
Arena Pharmaceuticals Inc.
Primary sponsor: Country of origin
United States of America
Public title
Etrasimod Versus Placebo for the Treatment of Moderately to Severely Active Ulcerative Colitis
Acronym
Scientific title
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, 52-Week Study to Assess the Efficacy and Safety of Etrasimod in Subjects With Moderately to Severely Active Ulcerative Colitis
Acronym
Brief summary of the study: English
The purpose of this study is to determine whether Etrasimod is a safe and effective treatment for moderately to severely active ulcerative colitis
Brief summary of the study: Arabic
الغرض من ھذه الدراسة ھو تحدید ما إذا كان Etrasimod ھو علاج آمن و فعال لالتھاب القولون التقرحي النشیط بشكل معتدل إلى شدید
Health conditions/problem studied: Specify
Ulcerative Colitis
Interventions: Specify
Drug: Etrasimod (APD334) 2mg tablet by mouth, once daily up to 52 weeks of treatment Drug: Placebo tablet by mouth, once daily up to 52 weeks of treatment
Key inclusion and exclusion criteria: Inclusion criteria
Inclusion criteria: Subjects must meet ALL of the following inclusion criteria to be eligible for enrollment into the study: 1. Men or women 16 to 80 years of age, inclusive, at the time of assent/consent 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 assessmentsDisease-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. Inclusion of subjects with proctitis only at baseline 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 prior to their first dose of study treatment. Prior 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 (TNFα) antibodies (eg, infliximab, adalimumab, golimumab, or biosimilars) b. Anti-integrin antibodies (eg, vedolizumab) c. JAK inhibitors (eg, tofacitinib) Note: The medication used to qualify the subject for entry into this category must be approved for the treatment of UC in the country of use. 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 (Note: Subjects on existing oral corticosteroid therapy will be tapered during the 40-Week Treatment Period.) • 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. Other general inclusion criteria: 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 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 12. 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 ≤ 3.0 × ULN. Subjects with an isolated total bilirubin and normal AST and ALT diagnosed with Gilbert’s syndrome may participate 13. Adequate renal function defined by an estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2 by the CKD-EPI equation at screening 14. Eligible women of childbearing potential must be: a. Nonpregnant, evidenced by a negative serum beta-human chorionic gonadotropin (β-hCG) pregnancy test at screening and a urine dipstick pregnancy test at Day 1 b. Not breastfeeding 15. Both men and women subjects agree to use a highly effective method of birth control throughout the entire study period, from informed consent through the adverse event reporting period (30 days after the last dose of study treatment), if the possibility of conception exists. Eligible men and women subjects must also agree not to participate in a conception process (ie, actively attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) during the study and for 30 days after the last dose of study treatment. Highly effective birth control methods include the following: • Oral, implantable, or injectable contraceptives (starting ≥ 60 days before dosing) in combination with a diaphragm with vaginal spermicide, cervical cap with vaginal spermicide, or male condom; hormonal contraceptives (subjects should be consistently taking the hormonal contraceptive for at least 3 months [90 days] prior to screening) • Standard intrauterine device (IUD; eg, Copper T 380A IUD), intrauterine system (IUS; eg, LNg 20 IUS - progesterone IUD), progesterone implant, or tubal sterilization (≥ 180 days after surgery) • Vasectomized male subjects using a condom, partner using diaphragm with spermicide, cervical cap with spermicide, estrogen and progesterone oral contraceptives (“the pill”), estrogen and progesterone transdermal patch, vaginal ring, or progesterone injection • Complete sexual abstinence defined as refraining from heterosexual intercourse for the entire period of risk associated with study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the subject. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not acceptable Note: Women who are surgically sterile or postmenopausal (defined as: 12 consecutive months with no menses without an alternative medical cause) are not considered to be of childbearing potential. If of childbearing potential, female partners of participating male subjects should agree to utilize a highly effective method of contraception for the duration of study participation.
Key inclusion and exclusion criteria: Gender
Both
Key inclusion and exclusion criteria: Age minimum
16
Key inclusion and exclusion criteria: Age maximum
80
Key inclusion and exclusion criteria: Exclusion criteria
Exclusions related to general health: 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 (ova and parasite examination, bacteria) or positive test for Clostridium difficile toxin at screening (If C. difficile is positive, the subject may be treated and retested ≥ 4 weeks after completing treatment) 6. Pregnancy, lactation, or a positive serum β-hCG measured during screening 7. Clinically relevant hematologic, hepatic, neurological, pulmonary, ophthalmological, endocrine, metabolic (including, but not limited to, hypo- and hyperkalemia), 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 2 months of the Screening Visit) of cardiovascular disease, including myocardial infarction or unstable angina 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 atrioventricular (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 as determined by hemoglobin A1c (HbA1c) > 9% 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. The following are EXCEPTIONS to this exclusion criteria: • Subjects with latent TB, who have been ruled out for active TB, have completed an appropriate course of TB prophylaxis treatment per national/local medical guidelines or WHO guidelines, and have not had recent close contact with a person with active TB are eligible to enroll in the study. It is the responsibility of the Investigator to verify the adequacy of previous TB treatment and provide appropriate documentation • Subjects diagnosed with latent TB at screening, ruled out for active TB and received at least 4 weeks of an appropriate TB prophylaxis regimen may be rescreened for enrollment Note: The 2 exceptions to this exclusion criterion outlined above do NOT apply to subjects in countries identified by WHO as a high multi-drug resistant TB burden country due to the high risk of latent infection with multi-drug resistance. 14. Known active bacterial, viral, fungal, mycobacterial infection, or other infection (including TB or atypical mycobacterial disease) 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 human immunodeficiency virus (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 (positive for hepatitis B surface antigen [HBsAg], or negative for HBsAg and positive for antihepatitis B core antibody in conjunction with detectable HBV DNA, or detectable HBV DNA) 17. 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 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) and 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 been excised and resolved) or colonic mucosal dysplasia 21. History of lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative disorder, or multiple myeloma 22. History of alcohol or drug abuse within 1 year prior to randomization Exclusions related to medications: 23. Prior treatment with sphingosine 1-phosphate receptor modulators 24. Treatment with a biologic agent within 8 weeks or 5 elimination half-lives, whichever is shorter, prior to randomization 25. Treatment with an investigational therapy within 3 months prior to randomization 26. Treatment failure with ≥ 3 biologic agents or ≥ 2 biologics plus a JAK inhibitor approved for treatment of UC 27. Treatment with topical rectal 5-ASA, short-chain fatty acid enemas, or steroids within 2 weeks of screening or during screening 28. Treatment with cyclosporine, tacrolimus, sirolimus, methotrexate, or mycophenolate mofetil within 16 weeks of screening 29. Receipt of a live vaccine within 4 weeks prior to randomization 30. Previous treatment with natalizumab 31. Previous treatment with lymphocyte-depleting therapies (eg, alemtuzumab, anti-CD4, cladribine, rituximab, ocrelizumab, cyclophosphamide, mitoxantrone, total body irradiation, bone marrow transplantation, alemtuzumab, daclizumab) 32. Previous treatment with D-penicillamine, leflunomide, or thalidomide 33. Treatment with IV immune globulin or plasmapheresis within 3 months prior to randomization 34. Chronic use of therapies that moderately/strongly inhibit/induce cytochrome P450 (CYP) 2C8 and 2C9 metabolism and inhibitors of UGT1A7 within 4 weeks prior to randomization
Type of Study
Type
Interventional
Type of intervention
Pharmaceutical
Trial scope
Other
Trial scope: Specify scope
Efficacy, Safety, Pharmacokinetics
Study design: Allocation
Randomized controlled trial
Study design: Masking
Blinded (masking used)
Study design: Control
Placebo
Study phase
3
Study design: Purpose
Treatment
Study design: Assignment
Parallel
IMP has market authorization
No
Name of IMP
APD334 (Etrasimod)
Type of IMP
Others
Type of IMP: Specify
Pharmaceutical
Pharmaceutical class
Highly selective sphingosine 1-phosphate (S1P) receptor modulator
Therapeutic indication
Ulcerative Colitis
Therapeutic benefit
Treatment of moderately to severely active ulcerative colitis (UC)
Biospecimen retention
Samples with DNA**
Biospecimen description
Both Samples with DNA and Samples without DNA will be processed
Target sample size
16
Actual enrollment target size
Date of first enrollment: Type
Anticipated
Date of first enrollment: Date
28/05/2020
Date of study closure: Type
Anticipated
Date of study closure: Date
14/02/2022
Recruitment status
Pending
Date of completion
25/09/2020
IPD sharing statement plan
No
IPD sharing statement description
N/A
Additional data URL
Summary Results
Secondary Identifying Numbers
Full name of issuing authority
Secondary identifying number
European Clinical Trials Database
EudraCT Number: 2018-003985-15
Clinicaltrials.gov
NCT03945188
Sources of Monetary or Material Support
Name
Arena Pharmaceuticals Inc. USA
Secondary Sponsors
Name
N/A
Contact for Public/Scientific Queries
Contact type
First name
Last name
Address
Country
Telephone
Email
Affiliation
Public
Hasan
Dakkak
Wahat Al Arab Building 3rd floor - Al Arab Street – Barbir, Beirut
Lebanon
0096170027779
hasan.dakkak@iqvia.com
IQVIA
Scientific
Chris
Cabell
6154 Nancy Ridge Dr. ▪ San Diego, CA 92121
United States of America
+18584537200
ccabell@arenapharm.com
Arena Pharmaceuticals
Centers/Hospitals Involved in the Study
Center/Hospital name
Name of principles investigator
Principles investigator speciality
Ethical approval
Hotel Dieu de France Hospital
Dr. Cesar Yaghi
Gastroenterology
Approved
American University of Beirut Medical Center
Dr. Alaa Sharara
Gastroenterology
Approved
Saint George University Medical Center
Dr. Said Farhat
Gastroenterology
Approved
Ethics Review
Ethics approval obtained
Approval date
Contact name
Contact email
Contact phone
American University of Beirut Medical Center
06/07/2020
Dr Deborah Mukherji
N/A
009611350000
Saint George Hospital University Medical Center
09/07/2020
Dr Michel Daher
NA
009611441000
Hotel Dieu de France
03/06/2020
Pr. Sami Richa
cue@usj. edu.lb
009611421229
Countries of Recruitment
Name
Australia
Austria
Belgium
Brazil
Bulgaria
Canada
Chile
China
Colombia
Croatia
Czech Republic
Denmark
Estonia
France
Germany
Hungary
India
Italy
Republic of Korea
Mexico
Republic of Moldova
Netherlands
Poland
Portugal
Romania
Russian Federation
Republic of Serbia
Slovakia
South Africa
Spain
Switzerland
Taiwan
Thailand
Turkey
Ukraine
United Kingdom
United States of America
Belarus
Latvia
Lithuania
Georgia
Lebanon
Health Conditions or Problems Studied
Condition
Code
Keyword
Ulcerative Colitis
Ulcerative colitis (K51)
Colitis, Ulcerative, Ulcer, Gastroenteritis, astrointestinal Diseases
Interventions
Intervention
Description
Keyword
Drug
APD334 (Etrasimod) 2mg tablet
Etrasimod
Drug
Matching Placebo tablet
Placebo
Primary Outcomes
Name
Time points
Measure
Proportion of Participants With Clinical Remission
Week 12
by Mayo Component Sub-scores
Proportion of Participants With Clinical Remission
Week 52
by Mayo Component Sub-scores
Key Secondary Outcomes
Name
Time points
Measure
Proportion of Participants Achieving Endoscopic Improvement
Week 52
Mayo Component Sub-scores
Proportion of Participants Achieving Endoscopic Improvement
Week 12
Mayo Component Sub-scores
Proportion of participants With Clinical Remission
Week 52
Mayo Component Sub-scores and no Corticosteroid use for ≥ 12 Weeks
Proportion of Participants With Mucosal Healing
Week 52
Geboes Index Scores
Proportion of Participants With Mucosal Healing
Week 12
Geboes Index Scores
Proportion of Participants With Clinical Remission
Week 12 and Week 52
Mayo Component Sub-scores
Trial Results
Summary results in Lebanon
Study results globally
Date of posting of results summaries
Date of first journal publication of results
Results URL link
Baseline characteristics
Participant flow
Adverse events
Outcome measures
URL to protocol files
Link(s) to publications related to the study
Changes History
Change
Date
Addition of N/A for secondary sponsor
29/09/2020
Addition of Lebanon in countries of recruitment
29/09/2020
Addition of AUBMC IRB approval (instead of HDF)
29/09/2020
Addition of SGUMC IRB approval
22/10/2020
Addition of MOH registration number: 1st IL granted on 20/10/2020
22/10/2020
Addition of HDF IRB approval
10/11/2020
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