The purpose of this study is to determine whether RPC1063 is safe and effective in the treatment of ulcerative colitis (UC).

• Register: EUCTR
• Last refreshed on: 5 April 2021
• Main ID: EUCTR2015-000319-41-NL
• Date of registration: 01/07/2015
• Prospective Registration: Yes
• Primary sponsor: Celgene International II Sàrl (CIS II)
• Public title: The purpose of this study is to determine whether RPC1063 is safe and effective in the treatment of ulcerative colitis (UC).
• Scientific title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Oral RPC1063 as Induction and Maintenance Therapy for Moderate to Severe Ulcerative Colitis - Efficacy and Safety Study of RPC1063 in Ulcerative Colitis
• Date of first enrolment: 26/01/2016
• Target sample size: 1050
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000319-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: yes; Other trial design description: Induction (Coh 1 & 3: Random PlaceboContr; Coh2: OpenLabel:);If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belarus, Belgium, Bulgaria, Canada, Croatia, Czech Republic, Czechia, Georgia, Germany, Greece, Hungary, Israel, Italy, Korea, Republic of, Latvia, Moldova, Republic of, Netherlands, New Zealand, Poland, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Ukraine, United Kingdom, United States

Contacts

• Name: Truenorth Study Information Center
• Affiliation: Celgene International II Sàrl

• Name: Truenorth Study Information Center
• Affiliation: Celgene International II Sàrl

Key inclusion & exclusion criteria

Inclusion criteria:
1. Must meet one of the following criteria:
-Male or female adult patients aged 18 to 75 years (at screening), inclusive for
Cohort 1 or Cohort 2, or
-Male or female adolescent patients aged 12 to < 18 years (at screening) with a body weight = 45 kg for Cohort 3.
Note: Countries or sites with local restrictions that prohibit enrollment of adolescents (aged 12 to<18 years) will only enroll patients who are aged 18 to 75 years, inclusive. Enrollment of adolescent patients will only begin after the applicable regulatory requirements for studying patients in that age group have been satisfied and the necessary health authority agreements have been granted.
2. Have had UC diagnosed at least 3 months prior to first investigational drug administration. The diagnosis should be confirmed by clinical and endoscopic evidence and corroborated by a histopathology report (note: endoscopy and histopathology may be performed at Screening if no prior report is readily available)
3. Evidence of UC extending = 15 cm from the anal verge as determined by Baseline endoscopy (flexible sigmoidoscopy or colonoscopy)
4. Have active UC defined as a complete Mayo score of 6 to 12 inclusive, with endoscopic subscore of = 2, a rectal bleeding score of = 1, and a stool frequency score = 1
5. Must be currently receiving treatment with at least 1 of the following therapies and must continue on these therapies during Induction:
- Oral aminosalicylates at a therapeutic dose for their disease (eg, mesalamine, sulfasalazine, olsalazine, balsalazide), with the dose stable for at least 3 weeks, prior to Screening endoscopy
- Prednisone (doses = 20 mg per day) or equivalent receiving a stable dose for at least 2 weeks prior to Screening endoscopy
- Budesonide MMX therapy receiving a stable dose for at least 2 weeks prior to Screening endoscopy
6. Have undergone colonoscopy (or are willing to undergo colonoscopy during Screening):
- within the past 2 years, to screen for dysplasia (unless otherwise recommended by local and national guidelines) if the patient has had left-sided colitis of > 12 years duration or total/extensive colitis of > 8 years duration
- within the past 5 years, to screen for polyps if the patient age is > 45 years
- 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 Baseline Mayo score
7. Females patients of childbearing potential (FCBP):
Must agree to practice a highly effective method of contraception throughout the trial until completion of the 90- day safety follow-up Visit. Highly effective methods of contraception are those that alone or in combination result in a failure rate of a Pearl index of less than 1% per year when used consistently and correctly. Acceptable methods of birth control in the trial are the following:
- combined hormonal (oestrogen and progestogen containing) contraception, which may be oral, intravaginal, or transdermal
- progestogen-only hormonal contraception associated with inhibition of ovulation, which may be oral, injectable, or implantable
- placement of an intrauterine device (IUD)
- placement of an intrauterine hormone-releasing system (IUS)
- bilateral tubal occlusion
- vasectomised partner
- complete sexual abstinence

All patients:
Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea me
Exclusion criteria:
Exclusions Related to General Health:
1. Have severe extensive colitis as evidenced by:
• Physician judgment that the patient is likely to require colectomy or ileostomy within 12 weeks of Baseline
• Current or recent (within 3 months) evidence of fulminant colitis, toxic megacolon, or bowel perforation
2. Diagnosis of Crohn’s disease or indeterminate colitis or the presence or history of a fistula consistent with Crohn’s disease or microscopic colitis or radiation colitis or ischemic colitis
3. Have positive stool examination for pathogens (ova and parasites, bacteria) or positive test for toxin producing Clostridium difficile (C. difficile) at Screening. PCR
(polymerase chain reaction) examination of the stool for C. difficile may be used to exclude false positives. If positive, patients may be treated and retested. Documentation of a negative test result for pathogens (ova and parasites, bacteria) is required within 60 days of Day 1.
4. Pregnancy, lactation, or a positive serum ß-human chorionic gonadotropin (ß-hCG) measured during Screening
5. Clinically relevant hepatic, neurological, pulmonary, ophthalmological, endocrine, psychiatric, or other major systemic disease making implementation of the protocol or interpretation of the trial difficult or that would put the patient at risk by participating in the trial
6. Clinically relevant cardiovascular conditions, including history or presence of:
• Recent (within the last 6 months) occurrence of myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, Class III/IV heart failure, sick sinus syndrome, or severe untreated sleep apnea
• For Adult patients: Prolonged Fridericia's corrected QT interval (QTcF; QTcF > 450 msec for males, > 470 msec for females), or at additional risk for QT interval prolongation
• For Adolescent patient: Prolonged Fridericia's corrected QT interval (QTcF; QTcF > 450 msec for both males amd females, or at additional risk for QT interval prolongation
• Resting HR < 55 bpm when taking vital signs as part of a physical exam at Screening
7. History of diabetes mellitus type 1, or uncontrolled diabetes mellitus type 2 with glycosylated Hb (HbA1c) > 9% , or diabetic patients with significant comorbid conditions such as retinopathy or nephropathy
8. History of uveitis (within the last year) or macular edema
9. Subject has a known active bacterial, viral, or fungal infection [excluding fungal infection of nail beds, minor upper respiratory tract infections, and minor skin infections] a mycobacterial infection (including tuberculosis[TB] or atypical mycobacterial disease),or any major episode of infection that required hospitalization or treatment with intravenous (IV) antibiotics within 30 days of Screening or oral antibiotics within 14 days of Screening
10. History of cancer, including solid tumors and hematological malignancies (except basal cell and in situ squamous cell carcinomas of the skin or uterine cervix that have been excised and resolved) or colonic mucosal dysplasia
11. History of alcohol or drug abuse within 1 year prior to randomization
Exclusions Related to Medications:
12. History of treatment with a biologic agent within 8 weeks or 5 elimination half-lives (whichever is less) of that agent prior to randomization
13. History of treatment with an investigational agent within 5 elimination half-lives of that agent prior to randomization
14. History of tr

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

ulcerative colitis
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Name: 0.25mg RPC103
Product Code: RPC1063
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ozanimod
Current Sponsor code: RPC1063
Other descriptive name: (S)-5-(3-(1-((2-hydroxyethyl)amino)-2,3-dihydro-1H-inden-4-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.25-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: 1.0 mg RPC103
Product Code: RPC1063
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ozanimod
Current Sponsor code: RPC1063
Other descriptive name: (S)-5-(3-(1-((2-hydroxyethyl)amino)-2,3-dihydro-1H-inden-4-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The efficacy endpoints will be formally examined with statistical hypothesis tests conducted on the efficacy results obtained from adult patients randomized and dosed in Cohort 1. Cohort 2 is open-label and does not contain a control group, therefore all of the efficacy endpoints
will be summarized and described without statistical hypothesis testing.
The analysis of adolescent patients (aged 12 up to < 18 years; (Cohort 3) wil be performed independently from the analysis of adult patients. Efficacy results in the Induction Period will be evaluated for similar efficacy trends between Cohort 1 and Cohort 3. No formal hypothesis testing is planned for Cohort 3 data.

INDUCTION PHASE Cohort 1
Primary Efficacy Endpoint:
- The proportion of adult patients in clinical remission at Week 10.

INDUCTION PHASE Cohort 2
Cohort 2 is open label; therefore no formal analysis of efficacy endpoints will be conducted.
All efficacy endpoints will be summarized and described without hypothesis testing.

MAINTENANCE PHASE
Primary Efficacy Endpoint:
- The proportion of adult patients in clinical remission at 52 weeks

Secondary Objective: INDUCTION THERAPY

Demonstrate
-the efficacy of RPC1063 versus placebo on induction of clinical response in adults
-the efficacy of RPC1063 versus placebo on achieving endoscopic improvement in adults
-the efficacy of RPC1063 versus placebo on achieving histologic remission in adults
-the safety and tolerability of RPC1063 induction therapy in all patients

MAINTENANCE THERAPY
Demonstrate
- in maintaining clinical response in adults
- on achieving endoscopic improvementin adults
- on durability of clinical remission in adults
-on maintaining clinical remission among patients who achieved remission during induction therapy in adults
- in achieving corticosteroid-free remission among patients receiving corticosteroids at entry into the Maintenance Period in adults
-the safety and tolerability of RPC1063 maintenance therapy in all patients

Timepoint(s) of evaluation of this end point: At 10 weeks (Induction Visit I4/Week 10)
At 52 weeks (Maintenance Visit M5/Week 42)

Main Objective: INDUCTION THERAPY
Demonstrate the efficacy of RPC1063 versus placebo on induction of clinical remission in adults.

MAINTENANCE THERAPY
To demonstrate the efficacy of RPC1063 versus placebo maintenance therapy on clinical remission in adults.

Secondary Outcome(s)

Secondary end point(s): INDUCTION PHASE
Key Secondary Efficacy Endpoints:
- The proportion of adult patients with a clinical response at Week 10
- The proportion of adult patients with endoscopic improvement at Week 10
- The proportion of adult patients with mucosal healing at Week 10

MAINTENANCE PHASE
Key Secondary Efficacy Endpoints:
- The proportion of adult patients with a clinical response at 52 weeks
- The proportion of adult patients with endoscopic improvement at 52 weeks
- The proportion of adult patients with durable clinical remission
- The proportion of adult patients in clinical remission at 52 weeks in the subset of patients who were
in remission at Week 10
- The proportion of adult patients with corticosteroid-free remission
- The proportion of adult patients with mucosal healing at 52 weeks

OTHER ENDPOINTS
Safety
Pharmacokinetic and pharmacodynamic

Timepoint(s) of evaluation of this end point: At 10 weeks (Induction Visit I4/Week 10)
At 52 weeks (Maintenance Visit M5/Week 42)
From the list of Other efficacy endpoints during maintenance phase (not primary or secondary) some endpoints are evaluated at 28 weeks (Maintenance Visit M3/Week 18), 40 weeks (Maintenance Visit M3/Week 30) and 52 weeks (Maintenance Visit M3/Week 42).

Secondary ID(s)

2015-000319-41-DE

RPC01-3101

NCT02435992

Source(s) of Monetary Support

Celgene International II Sàrl

Ethics review

Status: Approved
Approval date: 26/01/2016
Contact: