Clinical Trials Register

Summary
EudraCT Number:	2009-012500-11
Sponsor's Protocol Code Number:	205MS301
National Competent Authority:	Slovenia - JAZMP
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-01-10
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

Slovenia - JAZMP

A.2

EudraCT number

2009-012500-11

A.3

Full title of the trial

Multicenter, Double-blind, Randomized, Parallel-group, Monotherapy, Active-control Study to Determine the Efficacy and Safety of Daclizumab High Yield Process (DAC HYP) versus Avonex® (Interferon β 1a) in Patients with Relapsing-Remitting Multiple Sclerosis

A.3.1

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

Comparison of Daclizumab HYP and Avonex® in Multiple Sclerosis

A.3.2

Name or abbreviated title of the trial where available

DECIDE

A.4.1

Sponsor's protocol code number

205MS301

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 Ltd
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 Ltd
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
B.5.2	Functional name of contact point	Clinical trial information desk
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	decidestudy@biogenidec.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	DACLIZUMAB HYP
D.3.2	Product code	BIIB019
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Daclizumab wih Greek suffix
D.3.9.2	Current sponsor code	BIIB019
D.3.9.3	Other descriptive name	Daclizumab HYP (DAC HYP)
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	150
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	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	AVONEX
D.2.1.1.2	Name of the Marketing Authorisation holder	BIOGEN IDEC
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.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	INTERFERON BETA-1A
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
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	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 injection
D.8.4	Route of administration of the placebo	Subcutaneous use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Intramuscular use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Relapsing-remitting 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	14.1
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.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary study objective is to test the superiority of DAC HYP
compared to IFN β-1a in preventing MS relapse in subjects with
relapsing remitting MS (RRMS).

E.2.2

Secondary objectives of the trial

The secondary study objectives are to test the superiority of DAC HYP
compared to IFN β-1a in slowing functional decline and disability
progression and maintaining quality of life in this subject population.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

To be eligible for this study, candidates must meet the following
eligibility criteria prior to randomization or at the timepoint specified in
the individual criteria listed below:
1. Ability to understand the purpose and risks of the study and provide
signed and dated informed consent and authorization to use protected
health information (PHI) in accordance with national and local subject
privacy regulations.
2. Must be 18 to 55 years of age, inclusive, at the time of consent.
3. Must have a confirmed diagnosis of RRMS according to McDonald
criteria, numbers 1 through 4 (Polman et al, 2005), and a cranial MRI
demonstrating lesion(s) consistent with MS (it is not necessary to obtain a current scan if a scan performed previously is available; if a previous scan is not available, then the baseline scan may be used).
4. Must have a baseline EDSS between 0.0 and 5.0, inclusive.
5. Must meet one of the following disease activity-related criteria:
a) Two or more clinical relapses within the previous 3 years with at least
1 clinical relapse in the 12 months prior to randomization.
OR
b) One or more clinical relapses and 1 or more new MRI lesions (Gd+
and/or T2 hyperintense lesion) within the previous 2 years with at least
one of these events in the 12 months prior to randomization. The new
MRI lesion must be distinct from one associated with the clinical relapse.
The baseline MRI may be used to satisfy this criterion.
Note: For inclusion purposes, a clinical relapse is defined as neurologic
signs and/or symptoms documented in the medical record of at least 24 hours duration that are determined by the Investigator or the Treating Neurologist as consistent with an MS relapse. Time since relapse should be measured from the time of relapse onset. When inclusion is based on a new MRI lesion, activity must be verified by the central MRI reading center.
6. Women of childbearing potential must be willing to practice effective
contraception during the study and be willing and able to continue
contraception for 4 months after their last dose of study treatment.

E.4

Principal exclusion criteria

Medical History:
1. Diagnosis of primary progressive, secondary progressive, or
progressive relapsing MS (as defined by Lublin and Reingold, 1996).
2. Known intolerance, contraindication to, or history of non compliance
with Avonex 30 mcg.
3. 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.
4. History of severe allergic or anaphylactic reactions.
5. Known hypersensitivity to study drugs or their excipients.
6. History of abnormal laboratory results that, in the opinion of the
Investigator, are indicative of any significant cardiac, endocrine,
hematological, hepatic, immunologic, metabolic, urologic, pulmonary,
gastrointestinal, dermatologic, psychiatric, renal, neurological (other
than MS), and/or other major disease that would preclude
administration of DAC HYP or Avonex.
7. History of human immunodeficiency virus (HIV) or other
immunodeficient conditions.
8. History of drug or alcohol abuse (as defined by the Investigator)
within the 2 years prior to randomization.
9. History of seizure disorder or unexplained blackouts OR history of a
seizure within 6 months prior to Baseline.
10. History of suicidal ideation or an episode of clinically severe
depression (as determined by the Investigator) within 3 months prior to Day 1. Subjects receiving ongoing antidepressant therapy will not be
excluded from the study unless the medication has been increased
within the 6 months prior to Baseline.
11. An MS relapse that has occurred within the 50 days prior to
randomization AND/OR the subject has not stabilized from a previous
relapse prior to randomization.
12. Known history of, or positive screening test result for hepatitis C
virus or hepatitis B virus.
13. Varicella or herpes zoster virus infection or any severe viral infection
within 6 weeks before screening.
14. Exposure to varicella zoster virus within 21 days before screening.
15. Any of the following abnormal blood tests at screening:
• hemoglobin ≤9.0 g/dL
• platelets ≤100 x 10^9/L
• lymphocytes ≤1.0 x 10^9/L
• neutrophils ≤1.5 x 10^9/L
• alanine aminotransferase/serum glutamate pyruvate transaminase
(ALT/SGPT), aspartate aminotransferase/serum glutamic oxaloacetic
transaminase (AST/SGOT), or gamma glutamyl-transferase ≥2 times the upper limit of normal (ULN)
• serum creatinine ≥ULN
Treatment History:
16. Any previous treatment with daclizumab or other anti-CD25
monoclonal antibody.
17. Any type of live virus vaccine from 4 weeks before randomization,
including but not limited to, measles/mumps/rubella vaccine, varicella
zoster virus vaccine, oral polio vaccine, and nasal influenza vaccine.
18. Infection (viral, fungal, bacterial) requiring hospitalization or
intravenous (IV) antibiotics within 8 weeks before randomization.
19. Elective surgery performed from 2 weeks prior to randomization or
scheduled through the end of the study.
20. Treatment with another investigational drug or approved therapy for investigational use within the 6 months prior to randomization.
21. Prior treatment with the any of the following:
• total lymphoid irradiation
• cladribine
• T cell or T cell receptor vaccination
• any therapeutic monoclonal antibody, except natalizumab
22. Prior treatment with mitoxantrone, cyclophosphamide, fingolimod, or natalizumab within 1 year prior to randomization.
23. Prior treatment with any of the following medications or procedures
within the 6 months prior to randomization:
• cyclosporine
• azathioprine
• methotrexate
• mycophenolate mofetil
• intravenous immunoglobulin
• plasmapheresis or cytapheresis.
24. Treatment with any of the following medications within the 30 days
prior to randomization:
• IV corticosteroid treatment
• oral corticosteroid treatment
• glatiramer acetate
25. Initiation of treatment or dose adjustment of commercially-available
Fampridine-SR within the last 90 days.
Note: Subject who have been on a stable dose of commercially-available
Fampridine-SR for longer than 90 days are not excluded. Use of
compounded or other formulations of 4 - aminiopyridine is excluded.
Miscellaneous:
26. Female subjects who are currently pregnant or breastfeeding.
27. Female subjects considering becoming pregnant while in the study.
28. Previous participation in this study.
29. Subjects for whom MRI is contraindicated, i.e., have pacemakers or
other contraindicated implanted metal devices, are allergic to
gadolinium, or have claustrophobia that cannot be medically managed.
30. Unwillingness or inability to comply with the requirements of the
protocol, including the presence of any condition (physical, mental, or
social) that is likely to affect the subject's ability to comply with the
protocol.
31. Other medical reasons that, in the opinion of the Investigator and/or Biogen Idec, make the subject unsuitable for enrollment.

E.5 End points

E.5.1

Primary end point(s)

• Annualized relapse rate (ARR)

E.5.1.1

Timepoint(s) of evaluation of this end point

Any relapses and time on study that occur up to Week 144

E.5.2

Secondary end point(s)

a) Number of new or newly-enlarging T2 hyperintense lesions on brain
magnetic resonance imaging (MRI) over 96 weeks
b) Change in Multiple Sclerosis Functional Composite (MSFC) score
c) Sustained disability progression defined by at least a 1.0-point
increase on the Expanded Disability Status Scale (EDSS) from baseline
EDSS ≥1.0 that is sustained for 12 weeks or at least a 1.5-point increase on the EDSS from baseline EDSS <1.0 that is sustained for 12 weeks
d) Change in Multiple Sclerosis Impact Scale-29 (MSIS-29) physical
score
e) The proportion of subjects who are relapse-free

E.5.2.1

Timepoint(s) of evaluation of this end point

a) Weeks 0, 24, 96, (and also 144/early termination)
b) Screening, weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132,
144/early termination.
c) Screening, weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132,
144/early termination (and also follow up visits 1 and 2, and
unscheduled relapse assessment
d) Weeks 0, 24, 48, 72, 96, 120, 144
e) up to week 144 (end of study visit)

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

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

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

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)

Yes

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

123

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

Australia

Brazil

Canada

Czech Republic

Denmark

Finland

France

Germany

Greece

Hungary

India

Ireland

Israel

Italy

Mexico

Poland

Romania

Russian Federation

Serbia

Spain

Sweden

Switzerland

Ukraine

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

Last Visit Last Subject

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