Clinical Trials Register

Summary
EudraCT Number:	2017-001224-22
Sponsor's Protocol Code Number:	215MS202
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2017-09-01
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2017-001224-22

A.3

Full title of the trial

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study in Subjects With Relapsing Multiple Sclerosis to Evaluate the Efficacy and Safety of BIIB033 as an Add-On Therapy to Anti-Inflammatory Disease-Modifying Therapies

A.3.1

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

Efficacy and Safety of BIIB033 as an Add-on Therapy to Disease-Modifying Therapies (DMTs) in Relapsing Multiple Sclerosis (MS)

A.3.2

Name or abbreviated title of the trial where available

Efficacy and Safety of BIIB033 as an Add-on Therapy to DMTs in RMS

A.4.1

Sponsor's protocol code number

215MS202

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	Biogen Idec Research Limited
B.1.3.4	Country	United Kingdom
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	Biogen Idec Research Limited
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Biogen Idec Research Limited
B.5.2	Functional name of contact point	215MS202 Clinical Trial Team
B.5.3	Address:
B.5.3.1	Street Address	Innovation House, 70 Norden Road
B.5.3.2	Town/ city	Maidenhead, Berkshire
B.5.3.3	Post code	SL6 4AY
B.5.3.4	Country	United Kingdom
B.5.6	E-mail	clinicaltrials@biogen.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	Opicinumab
D.3.2	Product code	BIIB033
D.3.4	Pharmaceutical form	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	Opicinumab
D.3.9.3	Other descriptive name	BIIB033 (ANTI-LINGO)
D.3.9.4	EV Substance Code	SUB118957
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	200
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	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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Multiple Sclerosis

E.1.1.1

Medical condition in easily understood language

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	10067063
E.1.2	Term	Progressive relapsing 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	10063399
E.1.2	Term	Relapsing-remitting multiple sclerosis
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 efficacy and safety of BIIB033 used as add-on therapy to DMTs in subjects with relapsing multiple sclerosis (RMS).

E.2.2

Secondary objectives of the trial

Evaluate effects of BIIB033 versus placebo on additional measures of disability improvement
- Proportion of subjects with 12-week confirmed improvement in at least 1 of following assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND
- Proportion of subjects with 12-week confirmed improvement in at least 1 of the following assessments: EDSS, T25FW, 9HPT-D, 9HPT-ND, or 3-Second Paced
Auditory Serial Addition Test (PASAT-3)
- Proportion of subjects with 12-week confirmed improvement in at least 1 of following assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND, and without
confirmed worsening in any of 4 assessments during 72 weeks of study
- Proportion of subjects with 12-week confirmed improvement in at least 1 of the following assessments: EDSS, T25FW, 9HPT-D, 9HPT-ND, and Symbol Digit
Modalities Test (SDMT)
- Proportion of subjects with 12-week confirmed improvement in at least 1 of following assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND (20% thresholds
for T25FW and 9HPT)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Key Inclusion Criteria:
-Baseline Expanded Disability Status Scale (EDSS) of 2.0 to 6.0, have a diagnosis of relapsing-remitting multiple sclerosis (RRMS) per the 2010 McDonald’s criteria or onset of secondary progressive multiple sclerosis (SPMS) per the Lublin and Reingold criteria, and should have experienced their first MS symptom(s) within the previous 20 years.
-Subjects must have experienced at least 1 of the following within 24 months prior to Day 1/Baseline: a clinical relapse (but not within 24 weeks prior to Day 1/Baseline), gadolinium-enhancing lesions on brain or spinal cord magnetic resonance imaging (MRI), or new T2 lesion(s) on brain or spinal cord MRI.
-Subjects must be on a stable dose of a protocolspecified anti-inflammatory disease-modifying therapies
(DMT) (IFNβ [Avonex, Plegridy, Betaferon/Betaseron, or Rebif], dimethyl fumarate (DMF) [Tecfidera], or
natalizumab [Tysabri]) for at least 24 weeks prior to enrollment.
-In addition, subjects must have met protocol-defined MRI characteristics consistent with the presence of demyelination and relatively well-preserved tissue integrity. For enrollment, subjects must meet the following MRI criteria on the Screening/Baseline brain MRI: magnetization transfer ratio (MTR) in T2 lesions ≤-0.17 normalized MTR unit and diffusion tensor imaging (DTI) – radial diffusivity in T2 lesions ≤0.98 × 10-3 mm2/s

E.4

Principal exclusion criteria

Key Exclusion Criteria
-Primary progressive MS
-An MS relapse that has occurred within 24 weeks prior to Day 1/Baseline or the subject has not stabilized from a previous relapse at the time of Screening.
-Treatment with any chemotherapeutic agents (e.g., mitoxantrone, cyclophosphamide, cladribine), celldepleting
monoclonal antibodies (mAbs) (e.g., rituximab, ocrelizumab, alemtuzumab), total lymphoid irradiation, T-cell or T-cell receptor vaccination, or teriflunomide within 1 year prior to Day 1/Baseline.
-Treatment with other anti-inflammatory DMTs (e.g., GA, fingolimod, daclizumab) or plasmapheresis within 24 weeks prior to Day1/Baseline.
-Treatment with Botox for limb spasticity within 24 weeks before Day 1/Baseline.
-Contraindications to MRI, for example, presence of pacemakers or other implanted metal devices (excluding dental braces), an allergy to gadolinium renal impairment, or claustrophobia that cannot be medically managed.
-History of human immunodeficiency virus or other immunodeficient conditions.
-History of malignancy; however, subjects with a history of excised or treated basal cell carcinoma or fewer than 3 squamous cell carcinomas are eligible to participate in this study.

E.5 End points

E.5.1

Primary end point(s)

Overall Response Score
Overall Response Score is a multicomponent score based on 4 components: Expanded Disability Status Scale (EDSS),
Timed 25-Foot Walk (T25FW), 9-Hole Peg Test in the dominant hand (9HPT-D), and 9HPT in the nondominant hand (9HPTND). It assesses overall changes in disability over time. Overall Score ranges from +4 to -4. At each visit, each
component is given a score relative to baseline: -1 if threshold is met for worsening, 0 if no changes meet threshold
criteria, or +1 if threshold is met for improvement. The thresholds for T25FW and 9HPT are defined by a 15%
change from baseline (≥15% decrease from baseline for improvement and ≥15% increase from baseline for worsening). For EDSS, improvement is defined as a ≥1.0-point decrease in EDSS from a baseline score of ≤6.0, and worsening is defined as a ≥1-point increase from a baseline score of ≤5.5 or a ≥0.5-point increase from a baseline score equal to 6.0.

E.5.1.1

Timepoint(s) of evaluation of this end point

Assessed every 12 weeks from Baseline to Week 72

E.5.2

Secondary end point(s)

- Percentage of Participants with 12-week Confirmed Improvement in at least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND
- Percentage of Participants with 12-week Confirmed Improvement in at least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, 9HPT-ND, or 3-Second Paced Auditory Serial Addition Test (PASAT-3)
- Percentage of Participants with 12-week Confirmed Improvement in at least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND, and without confirmed worsening in any of the 4 assessments during the 72 weeks of the study
- Percentage of Participants with 12-week Confirmed Improvement in at least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, 9HPT-ND, and Symbol Digit Modalities Test (SDMT)
- Percentage of Participants with 12-week Confirmed Improvement in at least 1 of the Following Assessments: EDSS, T25FW, 9HPT-D, or 9HPT-ND (20% thresholds for T25FW and 9HPT)

E.5.2.1

Timepoint(s) of evaluation of this end point

Assessed every 12 weeks from Baseline to Week 72

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

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

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

Yes

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

Australia

Belgium

Canada

Czech Republic

France

Germany

Hungary

Israel

Italy

Netherlands

Poland

Spain

Sweden

Switzerland

United Kingdom

United States

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:

240

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

117

F.4.2.2

In the whole clinical trial

240

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)

None

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

2017-10-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-09-27

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2021-02-12

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