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: 6 July 2020
• Main ID: EUCTR2015-000319-41-GR
• Date of registration: 18/04/2018
• 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: 23/07/2018
• Target sample size: 900
• 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: 2 phases. Induction (Cohort1: Random PlaceboContr; Cohort2: OpenLabel); Maintenance (PlaceboContr); 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, France, Germany, Greece, Hungary, Israel, Italy, Korea, Republic of, Latvia, Netherlands, New Zealand, Poland, Russian Federation, Slovakia, South Africa, Spain, Ukraine, United Kingdom, United States

Contacts

• Name: Truenorth Study Information Center
• Affiliation: Receptos Services, LLC

• Name: Truenorth Study Information Center
• Affiliation: Receptos Services, LLC

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female patients aged 18 to 75 years (at screening), inclusive
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 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
7. 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
8. Female patients of childbearing potential: Must agree to practice a highly effective method of contraception throughout the trial until completion of the 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
- sexual abstinence
Male patients: Must agree to use a latex condom during sexual contact with women of childbearing potential while participating in the study until completion of the safety follow-up visit.
All patients: Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational
amenorrhoea method are not acceptable methods of contraception. Female condom and male condom should not be used together.
9. Must provide written informed consent and have the ability to be compliant with the schedule of protocol assessments
10. Patients must have documentation of positive Varicella zoster virus IgG antibody status or complete Varicella zoster virus vaccination at
least 30 days prior to randomization
Are the trial subjects unde
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
? - Prolonged Fridericia’s corrected QT interval (QTcF; QTcF > 450 msec for males, > 470 msec for females), or at additional risk for QT interval prolongation (eg, hypokalemia, hypomagnesemia, congenital long-QT syndrome)
? - 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. Known active bacterial, viral, fungal, mycobacterial infection, or other infection (including
tuberculosis [TB] or atypical mycobacterial disease [but excluding fungal infection of nail beds, minor upper respiratory tract infections and minor skin infections]) or any major episode of infection that required hospitalization or treatment with intravenous antibiotics within 30 days of Screening or oral antibiotics within 14 days of Screening
10. Recurrent or chronic infection (eg, hepatitis A, B, or C, human immunodeficiency virus (HIV); recurrent urinary tract are allowed.
11. 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
12. History of alcohol or drug abuse within 1 year prior to randomization
13. History of or currently active primary or secondary immunodeficiency
Exclusions Related to Medications:
14. History of treatment with a biologic agent within 8 weeks or 5 elimination half-lives (whichever is less) of that agent prior to randomization
15. History of treatment with an investigational agent within 5 el

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

Health Condition(s) or Problem(s) studied

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

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

Intervention(s)

Product Name: 0.25 mg RPC1063
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 RPC1063
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)

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

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

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

Secondary Objective: INDUCTION THERAPY

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

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

Primary end point(s): The efficacy endpoints will be formally examined with statistical hypothesis tests conducted on the efficacy results obtained from patients randomized and dosed in Cohort 1. Cohort 2 is open-label and does not contain a control group

INDUCTION PHASE Cohort 1
Primary Efficacy Endpoint:
- The proportion of 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 patients in clinical remission at 52 weeks

Secondary Outcome(s)

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

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

RPC01-3101

2015-000319-41-DE

NCT02435992

Source(s) of Monetary Support

Celgene International II Sàrl

Ethics review

Status: Approved
Approval date: 20/07/2018
Contact: