Clinical Trials Register

Summary
EudraCT Number:	2010-023856-97
Sponsor's Protocol Code Number:	205MS302
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-07-15
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2010-023856-97

A.3

Full title of the trial

A Multicenter, Single-Arm, Open-Label, Study to Evaluate
the Immunogenicity and Pharmacokinetics of BIIB019,
Daclizumab High Yield Process (DAC HYP), Prefilled
Syringe Administered by Subcutaneous Injection in
Subjects With Relapsing-Remitting Multiple Sclerosis

A.3.1

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

Study to Evaluate BIIB019, Daclizumab High Yield Process (DAC HYP), when administered by Pre-filled Syringe

A.3.2

Name or abbreviated title of the trial where available

OBSERVE

A.4.1

Sponsor's protocol code number

205MS302

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 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 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
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	neurologyclinicaltrials@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.3.9.2	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	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 objective of the study is to assess the
immunogenicity of DAC HYP 150 mg administered every
4 weeks by an SC injection using the pre-filled syringe (PFS) in subjects with RRMS.

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are
- to characterize the PK of DAC HYP (using intensive PK data ) following single and multiple doses of DAC HYP administered by the PFS in a subset of subjects with RRMS.
- to evaluate the effect of DAC HYP on the PK of probe drugs for CYP isoenzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A).

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

Intensive PK Sub-Study

The following daclizumab PK parameters will be
determined for subjects in the Intensive PK Sub-Study,
following DAC HYP administration at Day 1 (Week 0)
and at Week 20:
o maximum concentration (Cmax)
o time to reach maximum concentration (Tmax)
o area-under-the-curve from start to end of the
dosing interval (AUCτ)
o trough concentrations (Ctrough)
o apparent volume of distribution (V/F)
o elimination half-life (t½)
o apparent clearance (CL/F)
Additional PK parameters may be calculated as
appropriate during data analysis

TP-DI Sub-Study
• The following PK parameters for individual probe drugs will be determined for subjects in the TP-DI Sub Study:
Primary:
o area-under-the-curve from zero to infinity (AUC0–∞). If the extrapolated AUC >20%, AUC0-t where t is the time of last point with quantifiable data (tlast) may be considered if appropriate.
o dextromethorphan to dextrorphan urine concentration ratio
Secondary:
o Cmax
o CL/F
o omeprazole/hydroxyomeprazole concentration ratio at 2 hours postomeprazole dosing.
Additional PK parameters may be calculated as appropriate during data analysis.

E.3

Principal inclusion criteria

Main Inclusion Criteria
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. Aged 18 to 65 years old, inclusive, at the time of informed consent.
3. Must have a confirmed diagnosis of RRMS according to McDonald criteria, and a previous cranial MRI demonstrating lesion(s) consistent with MS.
4. Must have a baseline EDSS between 0.0 and 5.0.
5. Must have had 1 or more clinical relapses within the previous 2 years.
Inclusion Criteria for 3-Year Treatment Extension
1. Must have been compliant with the 205MS302 protocol during the initial 24-week treatment period and the 20-week washout period.
2. Must resume DAC HYP treatment ≤12 weeks after completion of the washout period
Inclusion Criteria for the TP-DI Sub-Study
1. Compliance with the 205MS302 protocol during the initial 24-week treatment period and through Week 40 of the 20-week washout period.
2. Must agree to resume DAC HYP treatment ≤12 weeks after completion of the washout period
3. Must have normal LFT results (total bilirubin ≤1.5 × ULN, ALT/AST ≤ 2 × ULN, and prothrombin time/partial thromboplastin time ≤1.2 × ULN).
4. Must have estimated creatinine clearance >60 mL/min.

E.4

Principal exclusion criteria

Exclusion Criteria
1. Diagnosis of primary progressive, secondary progressive, or
progressive relapsing MS
2. History of malignancy.
3. History of severe allergic or anaphylactic reactions.
4. History of abnormal laboratory results that is indicative of any significant major disease that would preclude administration of DAC HYP.
5. History of human immunodeficiency virus or other immunodeficient conditions.
6. MS relapse that has occurred within the 30 days prior to Day 1 AND/OR the subject has not stabilized from a previous relapse prior to Day 1.
7. History of, or positive screening test for hepatitis C or hepatitis B infection.
8. Varicella or herpes zoster virus infection within 6 weeks before screening.
9. Exposure to varicella zoster virus within 21 days before screening.
10. Any of the following abnormal blood tests at screening:
• hemoglobin ≤9.0 g/dL, platelets ≤100 x 109/L ,lymphocytes ≤1.0 x109/L, neutrophils ≤1.5 x 109/L
• (ALT)/(ALT/SGPT), (AST)/ (AST/SGOT), or (GGT) ≥2 ×ULN)
• serum creatinine ≥ULN
Treatment History
Any previous treatment with daclizumab or other anti-CD25 monoclonal antibody, total lymphoid irradiation, cladribine, T-cell or T-cell receptor vaccination or any therapeutic monoclonal antibody, except natalizumab.
Any live virus vaccine within the 4 weeks prior to Day 1.
12. Infections requiring hospitalization or IV antibiotics within the 8 weeks prior to Day 1.
13. Elective surgery performed within the 2 weeks prior to Day 1 or scheduled through the end of the study.
14. Treatment with another investigational drug or approved therapy for investigational use within the 6 months prior to Day 1.
15. Treatment with mitoxantrone, cyclophosphamide, fingolimod, or natalizumab within 1 year prior to Day 1.
16. Treatment with any of the following medications or procedures within the 6 months prior to Day 1:
• cyclosporine
• azathioprine
• methotrexate
• mycophenolate mofetil
• IV immunoglobulin (IVIg)
• Plasmapheresis/ cytapheresis
17. Treatment with any of the following medications within the 30 days prior to Day 1:
• IV or oral corticosteroid treatment
• glatiramer acetate
18. For subjects currently taking valproic acid, carbamazepine, lamotrigine, or phenytoin:
• Treatment with any of these agents ≤ 6 months prior to study entry
• Treatment with 2 or more of these agents for more than 6 months prior to study entry are excluded unless they reduce to ≤1 agent prior to study entry.
• Dose escalations of one of these agents within the 6 months prior to study entry are excluded
Current treatment with isoniazid, propylthiouracil, or nimesulide at the time of study entry .
Exclusion Criteria for 3-Year Treatment Extension
1. Subjects who permanently discontinued DAC HYP treatment in Study 205MS302 for any reason prior to the 20 week washout period.
2. ALT/SGPT, (AST/SGOT), or GGT ≥2xULN within 7 days prior to reinitiation of DAC HYP.
Additional Exclusion Criteria for Specific TP-DI Sub-Study
Subject permanently discontinued DAC HYP treatment in Study 205MS302 for any reason prior to Week 40.
Subject is positive for NAbs at Week 36.
Subject is on a regimen of therapeutic anticoagulation.
Subject has narrow angle glaucoma.
Use of any drug or supplement that inhibits or induces CYP1A2, CYP2C9, CYP2C19, CYP2D6, or CYP3A activity within 14 days or 5 halflives (whichever is longer) before the first dose of probe-drug cocktail.
Consumption of grapefruit or grapefruit-containing products within 3 days before the first dose of probe-drug cocktail. History of gastrointestinal malabsorption conditions or bleeding. History of hypersensitivity to midazolam, caffeine, warfarin, vitamin K, dextromethorphan, or omeprazole.

E.5 End points

E.5.1

Primary end point(s)

• Incidence of anti-DAC HYP binding antibodies
(ADAbs) through week 44
• Incidence of anti-DAC HYP neutralizing antibodies
(NAbs) through week 44

E.5.1.1

Timepoint(s) of evaluation of this end point

At every study visit as indicated in the Study Events section of the protocol

E.5.2

Secondary end point(s)

• Daclizumab population PK parameters including apparent clearance
(CL/F) and apparent volume of distribution (V/F)
• PK parameters for subjects in the intensive PK Sub-Study:
• maximum concentration (Cmax)
• time to reach maximum concentration (Tmax)
• area-under-the-curve from start to end of the dosing interval (AUC)
• trough concentrations (Ctrough)
• apparent volume of distribution (V/F)
• elimination half-life (t½)
• apparent clearance (CL/F)
• The following PK parameters for individual probe drugs will be determined for subjects in the TP-DI Sub Study:
Primary:
o area-under-the-curve from zero to infinity (AUC0–∞). If the extrapolated AUC >20%, AUC0-t where t is the time of last point with quantifiable data (tlast) may be considered if appropriate.
o dextromethorphan to dextrorphan urine concentration ratio
Secondary:
o Cmax
o CL/F
o omeprazole/hydroxyomeprazole concentration ratio at 2 hours post-omeprazole dosing

E.5.2.1

Timepoint(s) of evaluation of this end point

Daclizumab PK parameters: Weeks 0, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36,
44, 48, 52, 56, 68, 80, 92, 104, 116, 128, 140, 152, 164, 176, 188

Sub-study parameters: Weeks 0 and 20

TP-DI Sub-Study paramaters: Weeks 43, 48, 52, and 53

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

E.6.5

Efficacy

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

Yes

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

Yes

E.7.1.3.1

Other trial type description

Immunogenicity

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

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.8.3

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

Hungary

Poland

Russian Federation

Czech Republic

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:

120

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

F.4.2.2

In the whole clinical trial

120

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)

As per protocol.

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

2011-09-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-09-06

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-01-26

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials