205MS301

Biogen

225 Binney Street, Cambridge, United States, 02142

Biogen Study Medical Director, Biogen, clinicaltrials@biogen.com

Biogen Study Medical Director, Biogen, clinicaltrials@biogen.com

No

No

No

Final

28 Jul 2014

No

Yes

28 Jul 2014

No

The primary study objective is to test the superiority of Daclizumab High Yield Process (DAC HYP) compared with interferon β-1a (IFN β-1a) in preventing multiple sclerosis (MS) relapse in participants with relapsing remitting multiple sclerosis. The secondary study objectives are to test the superiority of DAC HYP compared with IFN β-1a in slowing functional decline and disability progression and maintaining quality of life in this participant population.

Written informed consent was obtained from each subject prior to evaluations being performed for eligibility. Subjects were given adequate time to review the information in the informed consent and were allowed to ask, and have answered, questions concerning all portions of the conduct of the study. Through the informed consent process each subject was made aware of the purpose of the study, the procedures, the benefits and risks of the study, the discomforts and the precautions taken. Any side effects or other health issues occurring during the study were followed up by the study doctor. Subjects were able to stop taking part in the study at any time without giving any reason.

11 May 2010

No

Yes

Poland: 451

United States: 217

Russian Federation: 198

Ukraine: 129

Serbia: 111

Italy: 97

Czech Republic: 85

United Kingdom: 70

France: 54

India: 50

Spain: 46

Germany: 40

Hungary: 36

Brazil: 34

Romania: 33

Sweden: 31

Greece: 26

Argentina: 24

Canada: 19

Moldova, Republic of: 17

Mexico: 15

Israel: 14

Denmark: 12

Ireland: 10

Australia: 8

Switzerland: 6

Georgia: 5

Finland: 3

1841

994

0

0

0

0

0

0

1841

0

0

Overall Study (overall period)

Randomised - controlled

Yes

Interferon beta-1A

Avonex

Solution for injection

Intramuscular use

Avonex was supplied in treatment kits that were dispensed to subjects at each visit and contained a sufficient supply of Avonex prefilled syringes and IM needles for each dosing interval. Subjects were instructed on how to perform injections at home.

Placebo to DAC HYP

Solution for injection

Subcutaneous use

Placebo to DAC HYP was prepared and administered in an identical manner to DAC HYP.

Daclizumab HYP

BIIB019

DAC HYP

Solution for injection

Subcutaneous use

The individual preparing the DAC HYP carefully reviewed the instructions provided in the Directions for Handling and Administration, which superseded all other references (e.g., the DAC HYP Investigator Brochure), and DAC HYP was administered by staff in the clinic at the monthly visits. Subjects received SC injections of DAC HYP in one or more of the following locations: the back of the upper arm, the thigh, or the abdomen.

Placebo to Avonex

Solution for injection

Intramuscular use

Placebo to Avonex was supplied in treatment kits, which was dispensed to subjects at each visit and contained a sufficient supply of Avonex placebo prefilled syringes and IM needles for each dosing interval. Subjects were instructed on how to perform injections at home.

Interferon beta-1a

Daclizumab High Yield Process

Interferon beta-1a

Daclizumab High Yield Process

Relapses are defined as new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the examining neurologist. Only relapses confirmed by Independent Neurology Evaluation Committee (INEC) are included in this analysis. Adjusted ARR was estimated from a negative binomial regression model adjusted for the baseline relapse rate, history of prior IFN beta use, baseline Expanded Disability Status Scale (EDSS; ≤ 2.5 vs > 2.5) and baseline age (≤ 35 vs > 35). Data after subjects switched to alternative MS medications are excluded.

Primary

Up to 144 weeks

Daclizumab High Yield Process v Interferon beta-1a

652

Pre-specified

0.55

2-sided

Interferon beta-1a v Daclizumab High Yield Process

652

Pre-specified

45

2-sided

Assessed by brain magnetic resonance imaging (MRI). Estimated from a negative binomial regression model, adjusted for baseline volume of T2 hyperintense lesions, history of prior IFN beta use and baseline age (≤ 35 vs > 35). To account for the timing of the MRI measurement, the logarithmic transformation of the scan number of the MRI assessment was included in the model as the 'offset' parameter. Observed data after subjects switched to alternative MS medications are excluded. Missing data are not imputed. Only observed new or newly enlarging T2 lesions at the last visit of the subject up to Week 96 visit are used in this analysis.

Secondary

up to 96 weeks

Sustained disability progression is defined as: 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 = 0 that is sustained for 12 weeks. The EDSS measures the disability status of people with multiple sclerosis on a scale that ranges from 0 to 10, with higher scores indicating more disability. Estimated proportion of subjects with progression is based on the Kaplan-Meier product limit method. Subjects were censored at the time of withdrawal/switch if they withdrew from study or switched to alternative MS medication without a progression. Subjects with a tentative progression at the End of Treatment Period Visit (or the last EDSS assessment prior to alternative MS start date) and no confirmation assessment were censored at their last EDSS assessment.

Secondary

Baseline through 144 weeks

Relapses are defined as new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the Examining Neurologist. Only relapses confirmed by INEC are included in this analysis. Data after subjects switched to alternative MS medications are excluded. The estimated proportion of subjects relapse-free at Week 144 is based on the Kaplan-Meier product limit method.

Secondary

144 weeks

The MSIS-29 is a 29-item disease-specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient’s perspective; it measures physical and psychological items. Worsening in the MSIS-29 physical score is defined as an increase of ≥ 7.5 points in the MSIS-29 physical score at 96 weeks compared to baseline. If a subject was missing data for less than 10 of the 20 items that make up the physical score, then the mean of the non-missing items were used for the missing items. If a subject was missing 10 or more of the 20 items that make up the physical score, or missing the questionnaire entirely, or if the questionnaire was completed after the subject switched to alternative MS medication, a random effects model was used to estimate the MSIS-29 physical score.

Secondary

Baseline and 96 weeks

All events were collected from Baseline through Week 164 (end of Post-dosing period).

Treatment emergent events are reported. Events are considered treatment emergent if they occurred on or after the first dosing date and up to 180 days after the last dosing date.

16.1

IFN beta-1a 30 mcg

DAC HYP 150 mg