Clinical Trials Register

Summary
EudraCT Number:	2009-015318-23
Sponsor's Protocol Code Number:	205MS203
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-06-08
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

Germany - PEI

A.2

EudraCT number

2009-015318-23

A.3

Full title of the trial

A Multicenter, Open-label, Extension Study to Evaluate the Long-term Safety and Efficacy of Daclizumab High Yield Process (DAC HYP) Monotherapy in Subjects with Multiple Sclerosis Who Have Completed Treatment in Study 205MS202 (SELECTION)

A.3.1

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

A study designed to determine safety and efficacy of Daclizumab High
Yield Process (DAC HYP) in patients with Multiple Sclerosis Who Have
Completed Treatment in a previous study, 205MS202 (SELECTION)

A.4.1

Sponsor's protocol code number

205MS203

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	UK SL64AY
B.5.3.4	Country	United Kingdom
B.5.6	E-mail	selectstudy@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 High Yield Process
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
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.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-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	19.0
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 assess the safety of extended treatment with DAC HYP monotherapy in subjects with RRMS.

E.2.2

Secondary objectives of the trial

To assess the long-term immunogenicity of DAC HYP and to assess the durability of response to DAC HYP in preventing MS relapse, slowing disability progression, and reducing new MS lesion formation in this study population.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Autoinjector Pharmacokinetics (PK) Substudy version 2.1 dated 14 September 2011

Primary Objective:
To compare the systemic exposure of daclizumab following SC administration of 150 mg DAC HYP using the single-use autoinjector to the systemic exposure following manual PFS injection.

Secondary Objective:
To compare local tolerability of SC administration of 150 mg DAC HYP using the single-use autoinjector to local tolerability following manual PFS injection.

2013-2014 Influenza Vaccine Substudy

The objective of the optional administration of the of the 2013-2014 trivalent seasonal influenza vaccine is to assess the effect of DAC HYP treatment on the immune response to licensed trivalent seasonal influenza vaccine, as defined by HI titer.

E.3

Principal inclusion criteria

1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use PHI in accordance with national and local subject privacy regulations.
2. Must be a subject from Study 205MS202 who completed at least 52 weeks and must have been compliant with the 205MS202 protocol in the opinion of the Investigator.
3. Women of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 4 months after their last dose of study treatment.

Autoinjector PK Substudy Inclusion Criteria:
To be eligible for enrollment into the autoinjector substudy, subjects must also meet the following eligibility criteria at the time of randomization into the substudy:
4. Ability to understand the purpose and risks of the substudy and provide signed and dated informed consent.
5. Must have received at least 6 consecutive monthly doses of 150 mg DAC HYP in Study 205MS203. Note: Subjects are allowed to receive both vialed material and PFS material prior to randomization.
6. Must have a Body Mass Index within the range 18 to 32 kg/m2, inclusive.

Inclusion criteria for the 2013-2014 Influenza Vaccine Substudy:
1. Subjects must provide specific informed consent for the 2013-2014 Influenza Vaccine Substudy
2. Subjects must have completed at least 3 months of uninterrupted therapy with DAC HYP prior to entering the 2013-2014 Influenza Vaccine Substudy

E.4

Principal exclusion criteria

1. Subjects with any significant change in their medical status from the previous study that would preclude administration of DAC HYP, including laboratory tests or a current clinically- significant condition that, in the opinion of the Investigator, would have excluded the subject's participation in the 205MS201 or 205MS202 studies. The Investigator must re review the subject's medical fitness for participation and must consider any diseases that would preclude treatment.
2. Any subject who has permanently discontinued study treatment in Study 205MS202 due to an AE.
3. Current enrollment in any investigational drug study other than
205MS202.
4. Ongoing treatment with any approved or experimental diseasemodifying treatment for MS.
5.For subjects currently taking valproic acid, carbamazepine, lamotrigine, or phenytoin: Subjects treated with any of these agents for fewer than 6 months prior to study entry are excluded from study participation unless they discontinue the agent(s) prior to study entry.*
- Subjects treated with 2 or more of these agents for more than 6
months prior to study entry are excluded from study participation unless they reduce to ≤1 agent prior to study entry.*
- Subjects who have had dose escalations of one of these agents within the 6 months prior to study entry are excluded from study participation unless they revert to a previous dose that had been used for at least 6 months prior to study entry or unless they discontinue the agent prior to study entry.*
*Subjects may use an alternative medication allowed by the protocol as needed.
Note: Subjects who have been taking 1 of these medications at a stable dose for at least 6 consecutive months prior to study entry may continue to receive the medication without alteration and are eligible for study participation.
6. Subjects who are currently receiving treatment with isoniazid,
propylthiouracil, or nimesulide at the time of study entry and are not able to discontinue the agent or change to an alternative medication allowed by the protocol prior to initiation of study treatment in this study.

7. 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.

Autoinjector PK Substudy Exclusion Criteria:
Subjects will be excluded from enrollment into the autoinjector substudy if any of the following exclusion criteria exist at the time of randomization into the substudy:
8. Any clinically significant adverse event, in the opinion of the Investigator, that is ongoing at the time of randomization.
9. ALT or AST greater than the upper limit of normal (>ULN). Testing must have been performed within 30 days prior to randomization.
10. Unwillingness or inability to comply with the requirements of the substudy.

Exclusion Criteria for the 2013-2014 Influenza Vaccine Substudy:
1. Subject has had a severe allergic reaction (e.g., anaphylaxis) to eggs, egg proteins (a vaccine component), or any other component of the trivalent seasonal influenza vaccine.
2. Subject has had a serious reaction to previous influenza vaccination.
3. Subject has a known latex allergy.
4. Subject was previously vaccinated for the 2013-2014 influenza season strain.
5. Subject had a respiratory illness in the 2 weeks preceding the planned vaccination with the 2013-2014 trivalent seasonal influenza vaccine.
6. Subject has any ongoing adverse event or laboratory abnormality in SELECTED that has resulted in suspension of DAC HYP treatment at the time of enrollment into the 2013-2014 Influenza Vaccine Substudy.
7. Subject has received in the last 3 months: blood products oral or intravenous corticosteroids intravenous immunoglobulins
8. Subject has received any vaccination in the last 4 weeks.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoints of the study are AEs, including SAEs, discontinuation of DAC HYP due to AEs, and withdrawals due to AEs.

The primary endpoint for the autoinjector PK substudy is: Daclizumab area-under-the-curve over the dosing interval (AUC0-) after substudy Dose 4

E.5.1.1

Timepoint(s) of evaluation of this end point

Clinical Adverse Events:
All treatment-emergent events during 205MS203 will be included in the evaluation of safety. Treatment emergent includes any event that either occurs or worsens in severity after the onset of study treatment in 205MS203.
Clinical Adverse Events over Time:
In order to assess whether the incidence of events changes over time, the incidence will also be summarized by time period.

Autoinjector PK Substudy:
After the first and fourth injection in the substudy at the following timepoints:
Pre-dose (30 minutes before the first injection) and post dose at 8hr, 24hr, 72 hr, 120 hr, 7 days, 10 days, 14 days, 21 days, and 28 days (prior to the next dose).

E.5.2

Secondary end point(s)

• Immunogenicity
• Sustained disability progression defined by at least a 1.0-point increase on the EDSS from a baseline EDSS ≥1.0 that is sustained for 12 weeks, or at least a 1.5-point increase on the EDSS from a baseline EDSS <1.0 that is sustained for 12 weeks
• Annual change in total number and volume of new or newly enlarging T2 hyperintense lesions, Gd-enhancing lesions, T1 hypointense lesions, and brain atrophy on brain MRI
• Annualized Relapse Rate (ARR)

Autoinjector PK Substudy: Additional daclizumab PK parameters for substudy Dose 4 including:
o Observed maximum concentration (Cmax)
o Time to reach maximum concentration (Tmax)
o Observed minimum concentration (Cmin) Local tolerability as assessed by the following:
o subject-reported injection site pain (visual analog scale [VAS])
o clinician injection site assessments

E.5.2.1

Timepoint(s) of evaluation of this end point

Immunogenicity -at baseline, every 12 weeks through week 48, at week 96, at week 144, at week 192, at week 240, at week 288, at final study visit, at relapse assessment if applicable, and at early termination visit if
applicable.
EDSS- at baseline, every 24 weeks, and at early termination visit if applicable
MRI - at baseline, week 48, 96, 192, 240, and 288.
ARR- annually

Autoinjector PK Substudy:
Additional PK parameters: After fourth injection
Injection site assessments: After first and fourth injections

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

Yes

E.6.13.1

Other scope of the trial description

Immunogenicity

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

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

India

Russian Federation

Ukraine

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

As stated in the Protocol

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