Clinical Trials Register

Summary
EudraCT Number:	2015-002500-91
Sponsor's Protocol Code Number:	RPC01-3001
National Competent Authority:	Croatia - MIZ
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-07-06
Trial results	View 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

Croatia - MIZ

A.2

EudraCT number

2015-002500-91

A.3

Full title of the trial

A Multi-Site, Open-Label Extension Trial of Oral RPC1063 in Relapsing Multiple Sclerosis

Multicentrični, otvoreni produžetak ispitivanja oralnog lijeka RPC1063 za relapsnu multiplu sklerozu

A.3.1

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

A Multi-Site, Open-Label Extension Trial of Oral RPC1063 in Relapsing Multiple Sclerosis

A.3.2

Name or abbreviated title of the trial where available

Open Label Extension (OLE) study

A.4.1

Sponsor's protocol code number

RPC01-3001

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 (CIS II)
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 (CIS II)
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	PSI CRO OU
B.5.2	Functional name of contact point	Project Manager
B.5.3	Address:
B.5.3.1	Street Address	Narva mnt. 90
B.5.3.2	Town/ city	Tallinn
B.5.3.3	Post code	10127
B.5.3.4	Country	Estonia
B.5.4	Telephone number	+37256262469
B.5.5	Fax number	+3726448888
B.5.6	E-mail	Violetta.Yakimets@psi-cro.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	No
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	0.25mg 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 HCl
D.3.9.2	Current sponsor code	RPC1063
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	No
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	1.0mg 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 HCl
D.3.9.2	Current sponsor code	RPC1063
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

Relapsing Multiple Sclerosis

E.1.1.1

Medical condition in easily understood language

Relapsing Multiple Sclerosis

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10048393
E.1.2	Term	Multiple sclerosis relapse
E.1.2	System Organ Class	10029205 - Nervous system 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

To characterize the long-term safety and tolerability of RPC1063 in patients with relapsing multiple sclerosis.

E.2.2

Secondary objectives of the trial

To characterize the long-term efficacy of RPC1063 in patients with relapsing multiple sclerosis.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

To be eligible to participate in this trial, patients must meet all of the following criteria:
1. Completed one of the parent trials: RPC01-201 or RPC01-301
2. Does not have a condition that would require withdrawal from one of the parent trials (RPC01-201 or RPC01-301)
3. Has no conditions requiring treatment with a prohibited concomitant medication
4. Is not receiving treatment with any of the following drugs or interventions within the corresponding timeframe:
At Baseline (Day 1)
CYP2C8 inhibitors (eg, gemfibrozil or clopidogrel) or inducers (eg, rifampicin)
Two weeks prior to Baseline (Day 1)
Monoamine oxidase inhibitors (eg, selegiline, phenelzine)
5. Ability to provide written informed consent and to be compliant with the schedule of protocol assessments
6. Female patients of childbearing potential:
Must agree to practice a highly effective method of contraception throughout the study 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 this study 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

All patients:
Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method (LAM) are not acceptable methods of contraception. Female condom and male condom should not be used together.

E.4

Principal exclusion criteria

Patients that have a condition that would require withdrawal from one of the parent trials (RPC01-201 or RPC01-301)

E.5 End points

E.5.1

Primary end point(s)

Safety Endpoints
Safety and tolerability will be characterized in this trial by the incidence, relationship, and type of adverse events, serious adverse events, and adverse events leading to withdrawal from the trial; the incidence, relationship, and type of laboratory abnormalities; vital signs; electrocardiogram results; and physical examination abnormalities. Suicidality (Columbia-Suicide Severity Rating Scale) will be assessed in the trial. In addition, descriptive characterization will be provided for adverse events of special interest including bradycardia and heart conduction abnormalities (electrocardiogram and vital signs), pulmonary effects (forced expiratory volume at 1 second, forced vital capacity, and diffusing capacity of the lung for carbon monoxide measurements), macular edema (optical coherence tomography), hepatic effects (liver function tests), serious or opportunistic infections, and malignancy (see Protocol Section 12.4.2 for the complete list of AESIs).

Exploratory measurements of immune response (eg, anti-SARS-CoV-2 serology) will be assessed from blood samples collected at trial visits and end of treatment, and the potential association between these measurements and selected endpoints related to safety and/or efficacy.

In addition, dependence and withdrawal symptoms will be assessed in at least 80 evaluable patients who discontinue study drug using the
following assessments: PWC-20, HADS, ESS , vital signs, and the C-SSRS. Changes from last on-study-drug assessment for each withdrawal scale
(PWC-20, HADS, ESS, C-SSRS and vital signs) to post study drug Day 1, 4, 7, 14, 21, and 90 will be summarized.

Efficacy Endpoints
- Annualized relapse rate
- Time to first relapse
- The number of new or enlarging hyperintense T2-weighted brain magnetic resonance imaging lesions at each visit
- The number of gadolinium-enhanced brain magnetic resonance imaging lesions at each visit
-Time to onset of disability progression as defined by a sustained worsening in Expanded Disability Status Scale of 1.0 points or more from baseline, confirmed after 3 months and after 6 months
-Proportion of patients who are free of gadolinium-enhanced lesions at each visit
- Proportion of patients who are free of new or enlarging T2 lesions at each visit
- Percent change in normalized brain volume (atrophy) on brain magnetic resonance imaging scans from Baseline at each visit
-Change in Multiple Sclerosis Functional Composite score from Baseline at each visit (including the Low-Contrast Letter Acuity Test measurement of visual function as a component)
-Change in Multiple Sclerosis Quality of Life 54 score from Baseline at each visit
-Changes in other magnetic resonance imaging variables including but not limited to, number and volume of gadolinium-enhanced T1 lesions, volume of T2 lesions, number of new or enlarging T2 lesions, volume of unenhancing T1 lesions, number of new unenhancing T1 lesions

E.5.1.1

Timepoint(s) of evaluation of this end point

Every 3 month visit, every 6 Month Visit for subjects who have completed their 3rd annual visit, follow-up visit and during the unscheduled relapse visit if applicablec

E.5.2

Secondary end point(s)

None

E.5.2.1

Timepoint(s) of evaluation of this end point

N/A

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

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.8.2.4

Number of treatment arms in the trial

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

199

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

New Zealand

South Africa

United States

Estonia

Latvia

Lithuania

Poland

Sweden

Bulgaria

Romania

Spain

Germany

Greece

Italy

Belarus

Belgium

Bosnia and Herzegovina

Croatia

Georgia

Hungary

Moldova, Republic of

Portugal

Russian Federation

Serbia

Slovakia

Ukraine

United Kingdom

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

LVLS

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:

2496

F.1.3

Elderly (>=65 years)

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

2407

F.4.2.2

In the whole clinical trial

2496

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)

All patients who are receiving clinical benefit from treatment with RPC1063 to continue to receive it until marketing authorization is obtained in their country, or until the Sponsor discontinues the development program.

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

2016-06-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-01-20

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-01-05

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