Clinical Trials Register

Summary
EudraCT Number:	2015-001600-64
Sponsor's Protocol Code Number:	RPC01-3102
National Competent Authority:	Slovakia - SIDC (Slovak)
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-08-27
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Slovakia - SIDC (Slovak)

A.2

EudraCT number

2015-001600-64

A.3

Full title of the trial

A Phase 3, Multicenter, Open-Label Extension Trial of Oral RPC1063 as Therapy for Moderate to Severe Ulcerative Colitis

Multicentrické, odslepené predĺžené skúšanie 3. fázy, perorálne podávaného RPC1063 pri liečbe stredne závažnej až závažnej
ulceróznej kolitídy

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.3.2

Name or abbreviated title of the trial where available

Efficacy and Safety Study of long-term RPC1063 in Ulcerative Colitis

A.4.1

Sponsor's protocol code number

RPC01-3102

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02531126

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Celgene International II Sàrl
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Celgene International II Sàrl
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Celgene International II Sàrl
B.5.2	Functional name of contact point	Truenorth Study Information Center
B.5.3	Address:
B.5.3.1	Street Address	3033 Science Park Road, Suite 300
B.5.3.2	Town/ city	San Diego, California
B.5.3.3	Post code	92121
B.5.3.4	Country	United States
B.5.4	Telephone number	+18442669299
B.5.6	E-mail	truenorth@quintiles.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	ZEPOSIA® (ozanimod)
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Corporation
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	0.25 mg RPC1063
D.3.2	Product code	RPC1063
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ozanimod
D.3.9.2	Current sponsor code	RPC1063
D.3.9.3	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
D.3.9.4	EV Substance Code	SUB175614
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	ZEPOSIA® (ozanimod)
D.2.1.1.2	Name of the Marketing Authorisation holder	Celgene Corporation
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	1.0 mg RPC1063
D.3.2	Product code	RPC1063
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ozanimod
D.3.9.2	Current sponsor code	RPC1063
D.3.9.3	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
D.3.9.4	EV Substance Code	SUB175614
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1.0
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Ulcerative colitis

E.1.1.1

Medical condition in easily understood language

ulcerative colitis

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10045365
E.1.2	Term	Ulcerative colitis
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Evaluate the long-term safety of RPC1063 for the treatment of all
patients with moderate to severe UC.
Evaluate the long-term efficacy of RPC1063 for the treatment of adult
patients with moderate to severe UC.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Previously participated in a trial of RPC1063 (eg, RPC01-3101 or
completed at least 1 year of the open-label period of RPC01-202) and
meet the criteria for participation in the open label extension as outlined
in the prior trial
2. Females 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
-vasectomized partner
-complete sexual abstinence
*For the purposes of this study, a female patient is considered to be of
childbearing potential if she has reached menarche, and 1) has not
undergone a hysterectomy (the surgical removal of the uterus) or
bilateral oophorectomy (the surgical removal of both ovaries) or 2) has
not been postmenopausal for at least 24 consecutive months (that is,
has had menses at any time during the preceding 24 consecutive
months)
**Contraception Education: Counselling about pregnancy precautions
and the potential risks of fetal exposure must be conducted for FCBP.
The Investigator will educate all FCBP about the different options of
contraceptive methods or abstinence, as appropriate, at the Screening
and Baseline Visits. The patient will be re-educated every time her
contraceptive measures/methods or ability to become pregnant
changes. The female patient's chosen form of contraception must be
effective by the time the female patient is randomized into the study (for
example, hormonal contraception should be initiated at least 28 days
before baseline).
Periodic abstinence (calendar, symptothermal, post-ovulation methods),
withdrawal (coitus interruptus), spermicides only, and lactational
amenorrhea method are not acceptable methods of contraception.
3. Must provide written informed consent and have the ability to
be compliant with the schedule of protocol assessments, which must be
obtained prior to any trial-related procedures. The parent/legal guardian
of the adolescent must sign an informed consent form. In addition,
adolescent patients must also agree to participate in the study by
signing an assent.

E.4

Principal exclusion criteria

Exclusions Related to Medications:
1. Have received any of the following therapies since the first dose of investigational drug in the prior RPC1063 trial:
• Treatment with a biologic agent
• Treatment with an investigational agent other than RPC1063
• Treatment with D-penicillamine, leflunomide, thalidomide, natalizumab, fingolimod, etrasimod, or tofacitinib
• Treatment with lymphocyte-depleting therapies (e.g., Campath, anti- CD4, cladribine, rituximab, ocrelizumab, cyclophosphamide, mitoxantrone, total body irradiation, bone marrow transplantation, alemtuzumab, daclizumab)
• Treatment with a live vaccine or live attenuated vaccine within 4 weeks prior to Visit 1 of this trial
2. Are currently receiving or require initiation of any of the following therapies:
• Treatment with corticosteroids at a dose that exceeds the prednisone equivalent of >40 mg
• Treatment with immunosuppressive agents (e.g., azathioprine, 6-MP, or methotrexate)
• Chronic non-steroidal anti-inflammatory drug (NSAID) use (Note: occasional use of NSAIDs and acetaminophen [eg, headache, arthritis, myalgias, or menstrual cramps] and aspirin up to 325 mg/day is
permitted)
• Treatment with Class Ia or Class III anti-arrhythmic drugs or treatment with two or more agents in combination known to prolong PR interval
3. Are receiving treatment with any of the following drugs or
interventions within the corresponding timeframe:
At Day 1
- CYP2C8 inhibitors (eg, gemfibrozil or clopidogrel) or inducers (eg,
rifampicin)
• Two weeks prior to Day 1
- Monoamine oxidase inhibitors (eg, selegiline, phenelzine)
4. Are receiving treatment with breast cancer resistance protein (BCRP)
inhibitors (eg, cyclosporine, eltrombopag)
Exclusions Related to General Health:
5. Pregnancy, lactation, or a positive serum beta human chorionic gonadotropin (hCG)
6. 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 or that would have required a patient to discontinue treatment in previous RPC1063 trial
7. Clinically relevant cardiovascular conditions, including history or presence of recent 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

Exclusions Related to Laboratory Results:
8. Liver function impairment or persisting elevations of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times the upper limit of normal (ULN), or direct bilirubin > 3 times the ULN
9. FEV1 or FVC < 50% of predicted values

E.5 End points

E.5.1

Primary end point(s)

Due to the open-label nature of the trial and the lack of a control group,
all data will be summarized and no hypothesis testing will be performed.
Each efficacy endpoint will be summarized and 95% confidence intervals
around the estimates may also be presented.
Efficacy Endpoints:
• Proportion of patients in clinical remission.
• Proportion of patients with a clinical response
• Proportion of patients with endoscopic improvement
• Proportion of patients with mucosal healing
• Proportion of patients with corticosteroid-free remission
• Change from Baseline in complete Mayo score, partial Mayo score, and
9-point Mayo score
• Proportion of patients with histologic remission
• Proportion of patients with clinical response, clinical remission, or
endoscopic improvement in patients who had previously received anti-
TNF therapy
Safety Endpoints:
-The incidence, severity, and relationship of treatment-emergent adverse
events (TEAEs), serious AEs (SAEs), TEAEs leading to discontinuation of
investigational drug, AEs of special interest (AESIs),
and TEAEs of special interest will be summarized.
- Exploratory safety endpoints include changes from baseline for clinical laboratory measures, vital signs, ECGs, and pulmonary function tests.
Other Exploratory Endpoints:
Absolute lymphocyte count (ALC) derived from hematology laboratory results
- Blood biomarkers (cytokines, chemokines, other markers of
inflammation)
- Stool biomarkers (eg FCP)
- Mucosal tissue blood biomarkers (eg, lymphocyte subsets)
- Exploratory measurements of immune response (e.g. SARS-CoV-2 serology), from blood samples (processed for serum only) collected after the amendment, every 48 weeks thereafter and end of treatment, and the potential association between these measurements and selected endpoints related to safety, efficacy, and/or biomarkers.

E.5.1.1

Timepoint(s) of evaluation of this end point

Efficacy assessments will be performed at the following visits;
Day 1 (Baseline/Visit 1) - All
Week 5 (Visit 2)
Week 10 (Visit 3)
Week 16 (Visit 4)
Week 22 (Visit 5)
Thereafter, additional visits at 24-week intervals (Visit 5 onwards).

Partial Mayo score assessment to be performed at each visit.
Full Mayo score assessment performed at Visit 1, Visit 7, and after that, at 48-week intervals (i.e.. Week 94, Week 142, etc.), and at the End of Treatment/Early Termination Visit.

Endoscopy and colonic biopsies will be performed at Week 1, Visit 7, and after that, at 48-week intervals (i.e.. Week 94, Week 142, etc.), and at the End of Treatment/Early Termination Visit.

E.5.2

Secondary end point(s)

Not applicable

E.5.2.1

Timepoint(s) of evaluation of this end point

Not applicable

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Djibouti

New Zealand

Moldova, Republic of

Ukraine

Australia

Belarus

Canada

Georgia

Israel

Korea, Republic of

Russian Federation

Serbia

South Africa

United Kingdom

United States

Belgium

Bulgaria

Croatia

Czechia

Germany

Greece

Hungary

Italy

Latvia

Netherlands

Poland

Romania

Slovakia

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Patients will receive treatment until the patient completes 5 years (Week 238) and the Safety Follow-up Visit, unless the Sponsor discontinues the development program.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

1164

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

614

F.4.2.2

In the whole clinical trial

1200

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Expected normal treatment for the condition

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-09-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-10-13

P. End of Trial
P.	End of Trial Status	Completed

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IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
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