Trial Outcomes & Findings for Safety and Efficacy Study of Daclizumab High Yield Process (DAC HYP) to Treat Relapsing-Remitting Multiple Sclerosis (NCT NCT00390221)

Last Updated: 2016-07-11

Results Overview

Relapses are defined as new or recurrent neurologic 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. The annualized relapse rate was calculated as the total number of relapses that occurred during the study divided by the total number of subject-years followed in the study.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

621 participants

Primary outcome timeframe

Baseline through Week 52

Results posted on

2016-07-11

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Placebo administered as 3 subcutaneous (SC) injections every 4 weeks for up to 52 weeks	150 mg DAC HYP 150 mg Daclizumab High Yield Process (DAC HYP) administered as 3 SC injections every 4 weeks for up to 52 weeks	300 mg DAC HYP 300 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks
Overall Study STARTED	204	208	209
Overall Study COMPLETED	186	188	194
Overall Study NOT COMPLETED	18	20	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo administered as 3 subcutaneous (SC) injections every 4 weeks for up to 52 weeks	150 mg DAC HYP 150 mg Daclizumab High Yield Process (DAC HYP) administered as 3 SC injections every 4 weeks for up to 52 weeks	300 mg DAC HYP 300 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks
Overall Study Lost to Follow-up	0	3	0
Overall Study Adverse Event	1	4	3
Overall Study Investigator Decision	0	0	1
Overall Study Withdrawal by Subject	13	9	7
Overall Study Subject Non-compliance	1	0	2
Overall Study Other	3	4	2

Baseline Characteristics

Safety and Efficacy Study of Daclizumab High Yield Process (DAC HYP) to Treat Relapsing-Remitting Multiple Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=204 Participants Placebo administered as 3 SC injections every 4 weeks for up to 52 weeks	150 mg DAC HYP n=208 Participants 150 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks	300 mg DAC HYP n=209 Participants 300 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks	Total n=621 Participants Total of all reporting groups
Age, Continuous	36.6 years STANDARD_DEVIATION 9.02 • n=5 Participants	35.3 years STANDARD_DEVIATION 8.94 • n=7 Participants	35.2 years STANDARD_DEVIATION 8.67 • n=5 Participants	35.7 years STANDARD_DEVIATION 8.88 • n=4 Participants
Age, Customized 18 to 19 years	1 participants n=5 Participants	4 participants n=7 Participants	5 participants n=5 Participants	10 participants n=4 Participants
Age, Customized 20 to 29 years	46 participants n=5 Participants	55 participants n=7 Participants	53 participants n=5 Participants	154 participants n=4 Participants
Age, Customized 30 to 39 years	79 participants n=5 Participants	73 participants n=7 Participants	90 participants n=5 Participants	242 participants n=4 Participants
Age, Customized 40 to 49 years	60 participants n=5 Participants	67 participants n=7 Participants	49 participants n=5 Participants	176 participants n=4 Participants
Age, Customized 50 to 55 years	18 participants n=5 Participants	9 participants n=7 Participants	12 participants n=5 Participants	39 participants n=4 Participants
Sex: Female, Male Female	128 Participants n=5 Participants	140 Participants n=7 Participants	134 Participants n=5 Participants	402 Participants n=4 Participants
Sex: Female, Male Male	76 Participants n=5 Participants	68 Participants n=7 Participants	75 Participants n=5 Participants	219 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline through Week 52

Population: Intent to treat population: all randomized participants who received at least 1 dose of study medication (excluding 21 participants from a single site due to a protocol violation in dosing).

Outcome measures

Outcome measures
Measure	Placebo n=196 Participants Placebo administered as 3 SC injections every 4 weeks for up to 52 weeks	150 mg DAC HYP n=201 Participants 150 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks	300 mg DAC HYP n=203 Participants 300 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks
Adjusted Annualized Relapse Rate Between Baseline and Week 52	0.458 relapses per person-years Interval 0.37 to 0.566	0.211 relapses per person-years Interval 0.155 to 0.287	0.230 relapses per person-years Interval 0.172 to 0.308

SECONDARY outcome

Timeframe: Week 8 through Week 24

Population: Magnetic Resonance Imaging (MRI) Intensive Population: a protocol-defined subset of participants consisting of the first 307 participants enrolled in the study with non-missing baseline values.

Gd-enhancing lesions are detected when Gd leaks into a perivascular space due to local breakdown of the blood-brain barrier, indicating the presence of active inflammation. For participants with missing data the last valid nonbaseline measurement was carried forward if the participant was missing only 1 or 2 consecutive postbaseline scans. Otherwise the mean based on treatment group and visit was used as the imputed value. Estimated from a negative binomial model adjusted for the baseline number of Gd-enhancing lesions.

Outcome measures

Outcome measures
Measure	Placebo n=104 Participants Placebo administered as 3 SC injections every 4 weeks for up to 52 weeks	150 mg DAC HYP n=101 Participants 150 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks	300 mg DAC HYP n=102 Participants 300 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks
Adjusted Mean Number of New Gadolinium (Gd)-Enhancing Lesions Between Week 8 and Week 24	4.79 lesions Interval 3.56 to 6.43	1.46 lesions Interval 1.05 to 2.03	1.03 lesions Interval 0.73 to 1.46

SECONDARY outcome

Timeframe: Week 52

Population: Intent to treat population: all randomized subjects who received at least 1 dose of study medication (excluding 21 subjects from a single site due to a protocol violation in dosing) with a non-missing value at baseline.

Lesions detected on T2-weighted sequences represent a range of histopathology related to MS, including edema, inflammation, demyelination, gliosis, and axon loss.

Outcome measures

Outcome measures
Measure	Placebo n=195 Participants Placebo administered as 3 SC injections every 4 weeks for up to 52 weeks	150 mg DAC HYP n=199 Participants 150 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks	300 mg DAC HYP n=200 Participants 300 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks
Adjusted Mean Number of New or Newly-enlarging T2 Hyperintense Lesions at Week 52	8.13 lesions Interval 6.65 to 9.94	2.42 lesions Interval 1.96 to 2.99	1.73 lesions Interval 1.39 to 2.15

SECONDARY outcome

Timeframe: Week 52

Estimated cumulative proportion of participants relapsed at Week 52, based on the Kaplan-Meier product limit method. Only relapses confirmed by the Independent Neurology Evaluation Committee were included in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=196 Participants Placebo administered as 3 SC injections every 4 weeks for up to 52 weeks	150 mg DAC HYP n=201 Participants 150 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks	300 mg DAC HYP n=203 Participants 300 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks
Proportion of Participants Who Relapsed at Week 52	0.36 proportion of participants	0.19 proportion of participants	0.20 proportion of participants

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: Intent to treat population: all randomized subjects who received at least 1 dose of study medication (excluding 21 subjects from a single site due to a protocol violation in dosing).

The 29-item Multiple Sclerosis Impact Scale (MSIS-29) is a 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 20 physical items and 9 psychological items. Responses use a 5 point Likert scale range from 1 to 5. All questions are to be answered. The total score is the sum of points for all 29 questions, with a minimum score of 29, and a maximum score of 145. A lower total score indicates less physically-related impact while a higher total score indicates greater physically-related impact on a subject's functioning.

Outcome measures

Outcome measures
Measure	Placebo n=196 Participants Placebo administered as 3 SC injections every 4 weeks for up to 52 weeks	150 mg DAC HYP n=201 Participants 150 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks	300 mg DAC HYP n=203 Participants 300 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks
Mean Change From Baseline in Multiple Sclerosis Impact Scale (MSIS)-29 Physical Impact Score at Week 52	3.0 units on a scale Standard Deviation 13.52	-1.0 units on a scale Standard Deviation 11.80	1.4 units on a scale Standard Deviation 13.53

Adverse Events

Placebo

Serious events: 53 serious events

Other events: 128 other events

Deaths: 0 deaths

150 mg DAC HYP

Serious events: 32 serious events

Other events: 109 other events

Deaths: 0 deaths

300 mg DAC HYP

Serious events: 36 serious events

Other events: 111 other events

Deaths: 0 deaths

Total Active

Serious events: 68 serious events

Other events: 220 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=204 participants at risk Placebo administered as 3 SC injections every 4 weeks for up to 52 weeks	150 mg DAC HYP n=208 participants at risk 150 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks	300 mg DAC HYP n=209 participants at risk 300 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks	Total Active n=417 participants at risk 150 mg or 300 mg DAC HYP administered as 3 SC injections every 4 weeks for up to 52 weeks
General disorders Pyrexia	0.98% 2/204 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	3.4% 7/208 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	7.2% 15/209 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	5.3% 22/417 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.
Infections and infestations Influenza	5.4% 11/204 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	2.4% 5/208 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	5.7% 12/209 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	4.1% 17/417 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.
Infections and infestations Nasopharyngitis	15.2% 31/204 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	14.4% 30/208 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	14.4% 30/209 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	14.4% 60/417 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.
Infections and infestations Oral herpes	4.9% 10/204 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	4.8% 10/208 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	6.2% 13/209 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	5.5% 23/417 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.
Infections and infestations Pharyngitis	4.4% 9/204 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	6.2% 13/208 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	6.2% 13/209 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	6.2% 26/417 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.
Infections and infestations Respiratory tract infection	5.4% 11/204 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	3.4% 7/208 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	6.2% 13/209 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	4.8% 20/417 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.
Infections and infestations Upper respiratory tract infection	6.9% 14/204 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	8.7% 18/208 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	10.5% 22/209 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	9.6% 40/417 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.
Investigations Alanine aminotransferase increased	2.0% 4/204 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	4.3% 9/208 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	5.7% 12/209 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	5.0% 21/417 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.
Nervous system disorders Headache	10.3% 21/204 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	9.6% 20/208 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	9.6% 20/209 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	9.6% 40/417 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.
Nervous system disorders Multiple sclerosis relapse	35.8% 73/204 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	21.6% 45/208 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	18.2% 38/209 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	19.9% 83/417 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.
Psychiatric disorders Depression	1.5% 3/204 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	4.8% 10/208 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	5.7% 12/209 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	5.3% 22/417 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.
Skin and subcutaneous tissue disorders Rash	2.9% 6/204 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	5.3% 11/208 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	5.3% 11/209 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.	5.3% 22/417 • AEs and SAEs were collected from the Screening Visit (≤ 21 Days prior to Baseline) through the Follow-Up Visit (Week 72 ± 5 days) or early discontinuation.

Additional Information

Biogen Study Medical Director

Biogen

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
Publication restrictions are in place

Restriction type: OTHER