Clinical Trials Register

Summary
EudraCT Number:	2017-004886-29
Sponsor's Protocol Code Number:	MN39158
National Competent Authority:	Slovenia - JAZMP
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-12-23
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

Slovenia - JAZMP

A.2

EudraCT number

2017-004886-29

A.3

Full title of the trial

A SINGLE ARM, OPEN LABEL MULTICENTRE EXTENSION STUDY TO EVALUATE THE EFFECTIVENESS AND SAFETY OF OCRELIZUMAB IN
PATIENTS WITH MULTIPLE SCLEROSIS PREVIOUSLY ENROLLED IN A F. HOFFMANN-LA ROCHE SPONSORED OCRELIZUMAB PHASE IIIb/IV CLINICAL TRIAL

Odprta, multicentrična nadaljevalna raziskava z eno skupino za oceno učinkovitosti in varnosti okrelizumaba pri bolnikih z multiplo sklerozo, predhodno vključenih v klinično preskušanje okrelizumaba faze IIIb/IV sponzorja F. Hoffmann-La Roche

A.3.1

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

A Study to Evaluate the Effectiveness and Safety of Ocrelizumab in Patients with Multiple Sclerosis Previously Enrolled in A F. Hoffmann-la Roche Sponsored Ocrelizumab Clinical Trial

A.4.1

Sponsor's protocol code number

MN39158

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	F. Hoffmann-La Roche Ltd
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	F. Hoffmann-La Roche Ltd
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	F. Hoffmann-La Roche Ltd
B.5.2	Functional name of contact point	Trial Information Support Line-TISL
B.5.3	Address:
B.5.3.1	Street Address	Grenzacherstrasse 124
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4070
B.5.3.4	Country	Switzerland
B.5.6	E-mail	global.rochegenentechtrials@roche.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	Ocrelizumab
D.3.2	Product code	RO4964913
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ocrelizumab
D.3.9.1	CAS number	637334-45-3
D.3.9.2	Current sponsor code	RO4964913
D.3.9.3	Other descriptive name	OCRELIZUMAB
D.3.9.4	EV Substance Code	SUB121707
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	Yes
D.3.11.13.1	Other medicinal product type	humanized monoclonal antibody
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	Ocrevus
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration GmbH
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Ocrelizumab
D.3.2	Product code	RO4964913
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ocrelizumab
D.3.9.1	CAS number	637334-45-3
D.3.9.2	Current sponsor code	RO4964913
D.3.9.3	Other descriptive name	OCRELIZUMAB
D.3.9.4	EV Substance Code	SUB121707
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	Yes
D.3.11.13.1	Other medicinal product type	humanized monoclonal antibody

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

Multiple sclerosis (MS)

E.1.1.1

Medical condition in easily understood language

MS is a chronic autoimmune neurological disease that affects the brain and spinal cord (central nervous system).

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	20.1
E.1.2	Level	PT
E.1.2	Classification code	10028245
E.1.2	Term	Multiple sclerosis
E.1.2	System Organ Class	10029205 - Nervous system disorders

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.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10063399
E.1.2	Term	Relapsing-remitting multiple sclerosis
E.1.2	System Organ Class	10029205 - Nervous system disorders

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	10039720
E.1.2	Term	Sclerosis multiple
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 evaluate the effectiveness of ocrelizumab therapy in MS patients who were previously enrolled in a Roche sponsored phase IIIb/IV-trial

E.2.2

Secondary objectives of the trial

• Different effectiveness measures evaluated for ocrelizumab in MS patients who were previously enrolled in a Roche sponsored phase IIIb/IV-trial
• To evaluate the safety and tolerability of ocrelizumab therapy in MS patients who were previously enrolled in a Roche sponsored phase IIIb/IV-trial

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Able to comply with the study protocol, in the investigator's judgment
- Eligible for roll-over into the MN39158/LIBERTO study (including the
female patients who were pregnant during the parent studies and are
still in the safety follow up period) based on the investigator decision in
a Roche sponsored ocrelizumab P-trial upon risk/benefit assessment for
continuous treatment with ocrelizumab
- Meet re-treatment criteria with ocrelizumab

E.4

Principal exclusion criteria

- Hypersensitivity to ocrelizumab or to any of its excipients
- Patients in a severely immunocompromised state until the condition resolves
- Evidence of any adverse event potentially attributable to ocrelizumab, for which the local label recommends permanent discontinuation
- Existence of a contra-indication as per ocrelizumab package leaflet
- Prohibited concomitant medication use
- Patients intending to become pregnant during the study or within 6 months after the last dose of the study drug in the parent study
- Patients who discontinued ocrelizumab, exemption made for treatment discontinuation due to pregnancy and breastfeeding for patients who continued clinical study assessments in the safety follow-up of the parent study

E.5 End points

E.5.1

Primary end point(s)

1. Evaluate clinical measures related to disease progression over the
duration of treatment in MS patients

E.5.1.1

Timepoint(s) of evaluation of this end point

1. Up to 2 years

E.5.2

Secondary end point(s)

1. Time to onset of Confirmed disability progression (CDP) sustained for
at least 24 weeks and for at least 48 weeks
2. Proportion of patients who have confirmed disability improvement
(CDI), CDP for at least 24 weeks and for at least 48 weeks yearly and
over the duration of treatment
3. Proportion of patients who have improved, stable or worsened
disability compared with baseline (inclusion in the study) measured by
expanded disability status scale (EDSS)'
4. Mean change from inclusion in the parent-study in EDSS score over
the course of treatment
5. Time to 20% increase in timed 25-foot walk test (T25FWT); time to
20% increase in timed nine-hole peg test (9HPT) sustained for at least
24 weeks and for at least 48 weeks, and proportion of patients achieving
a sustained increase assessed yearly and over the duration of treatment
6. Time to first protocol-defined event of disease activity
7. Time to first relapse
8. Annualized relapse rate
9. Proportion of patient relapse free, yearly and over the course of
treatment
10. Proportion of patients with no evidence of protocol-defined disease
activity (NEDA) yearly and over the duration of the treatment
11. Proportion of patients with no evidence of progression, measured by
EDSS, 9HPT and T25FW (if assessments are available)
12. Proportion of patients with no evidence of progression sustained for
at least 24 weeks and no active disease (if assessments are available)
13. Change from baseline (parent trial) in cognitive performance as
measured by the Symbol digit modalities test (SDMT)
14. Total number of T1 Gd-enhancing lesions as detected by brain MRI
over time
15. Total number of new and/or enlarging T2 lesion as detected by brain
MRI over time
16. Change in total T1 hypointense lesion volume over time
17. Total number of fluid-attenuated inversion-recovery (FLAIR) late
enhancing lesions as detected by brain MRI over time (pertinent to
CASTING/MA30005 patients only)
18. Total number of FLAIR late enhancing lesions as detected by brain
MRI at the end of the treatment period
19. Change in brain volume (including white and grey matter fractions)
as detected by brain MRI over time
20. Presence and evolution of leptomeningeal follicles (pertinent to
ENSEMBLE/MA30143 patients with identified FLAIR late enhancing
lesions and CASTING /MA30005 patients)
21. Time to treatment discontinuation/switch
22. Employment status (Work Productivity and Activity Impairment
Questionnaire [WPAI])
23. SymptoMScreen score
24. Quality of life (Multiple Sclerosis Impact Scale [MSIS]-29)
25. Rate and nature of adverse events
26. Changes in vital signs, neurological examinations, clinical laboratory
results, locally reviewed MRI for safety (non-MS CNS pathology) and
concomitant medications

E.5.2.1

Timepoint(s) of evaluation of this end point

1-26. Up to 2 years

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

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

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

Brazil

Mexico

Turkey

E.8.7

Trial has a data monitoring committee

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

The end of the study is defined as the last patient last visit (LPLV) in the B-cell monitoring of the Follow-Up period i.e. until B-cell repletion and no longer than 2 years (If the patients are receiving B-cell depleting therapies, then the Follow-up Period is only 48 weeks from the start of B-cell depleting therapies).
The total length of the study is expected to be dependent on the end of treatment of the last patient rolling over from the last parent study.

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

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:

659

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

409

F.4.2.2

In the whole clinical trial

659

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)

The Sponsor will offer continued access to Roche IMP (ocrelizumab) free of charge to eligible patients in accordance with the Roche Global Policy on Continued Access to Investigational Medicinal Product, as outlined in protocol section 4.3.5.

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

2021-03-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-12-16

P. End of Trial
P.	End of Trial Status	Ongoing

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