SELECTED: Safety and Efficacy Extension Study of Daclizumab High Yield Process (DAC HYP) (BIIB019) in Participants Who Have Completed Study 205MS202 (NCT00870740) to Treat Relapsing Remitting Multiple Sclerosis

• Sponsor: Biogen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01051349
• Collaborator: AbbVie (Industry)
• Enrollment: 410
• Locations: 65
• Arm: 1
• Actual Duration (Months): 76.8
• Patients Per Site: 6.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Primary Objective is to assess the safety of extended treatment with Daclizumab High Yield Process (DAC HYP, BIIB019) monotherapy in participants with relapsing remitting multiple sclerosis (RRMS). Secondary Objective is to assess the long-term immunogenicity of DAC HYP and to assess the durability of response to DAC HYP in preventing multiple sclerosis (MS) relapse, slowing disability progression, and reducing new MS lesion formation in this study population.

Condition or Disease	Intervention/Treatment	Phase
Relapsing-Remitting Multiple Sclerosis	Biological: BIIB019 (Daclizumab); Biological: trivalent seasonal influenza vaccine	Phase 2

Detailed Description

This study will provide participants who complete Study 205MS202 (NCT00870740) with the option to receive continued open-label Daclizumab High Yield Process (DAC HYP) monotherapy and to evaluate the long-term safety, efficacy, and immunogenicity of DAC HYP monotherapy in participants with relapsing remitting multiple sclerosis (RRMS). Approximately 60 to 100 participants will be enrolled into an optional open-label, 16-week autoinjector substudy at a selected subset of sites which will run concurrently during the main study, and will evaluate the systemic exposure and local tolerability of subcutaneous administration of DAC HYP by autoinjector. The 2013-2014 trivalent influenza vaccine will be offered to all eligible participants as an optional substudy to assess the effect of DAC-HYP treatment on the immune response to vaccination,

Study Design

• Study Type: Interventional
• Actual Enrollment: 410 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: Mar 31, 2010
• Actual Primary Completion Date: Aug 25, 2016
• Actual Study Completion Date: Aug 25, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BIIB019 Participants received BIIB019, 150 mg subcutaneous injection every 4 weeks up to Week 288.	Biological: BIIB019 (Daclizumab); Administered as specified in the treatment arm.; Other Names: Daclizumab High Yield Process DAC HYP ; Biological: trivalent seasonal influenza vaccine; All participants who participate in the 2013-2014 influenza vaccine substudy will receive the vaccine at the study site

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, Withdrawals Due to AEs [Baseline up to 24 weeks after last dose of treatment (Up to 300 weeks)]

   An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A SAE is any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important due to other reasons than the above mentioned criteria.

2. Area Under the Concentration-Time Curve Over the Dosing Interval (AUC0-t) After Dose 4 for Daclizumab [Day 90 (Week 12) at predose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14, 21 and 28 days post-dose]

Secondary Outcome Measures

1. Number of Participants With New or Newly Enlarging T2 Hyperintense Lesions Compared to Baseline [From Baseline through 288 weeks]

   New or newly enlarging T2 hyperintense lesions evaluated by magnetic resonance imaging (MRI) and analyzed by a central reader.

2. Annual Change in Volume of New or Newly Enlarging T2 Hyperintense Lesions Compared to Baseline [From Baseline through 288 weeks]

   New or newly enlarging T2 hyperintense lesions evaluated by MRI and analyzed by a central reader.

3. Number of Participants With Total Number of New Gadolinium-enhancing Lesions [From Baseline through 288 weeks]

   New Gadolinium-enhancing lesions was evaluated by MRI and analyzed by a central reader.

4. Annual Change in Number of T1 Hypointense Lesions [From Baseline through 288 weeks]

5. Annual Change in Volume of New Gadolinium-Enhancing Lesions [From Baseline through 288 weeks]

6. Annual Change in Volume of T1 Hypointense Lesions [From Baseline through 288 weeks]

   Volume of T1 hypointense lesions was evaluated by MRI and analyzed by a central reader.

7. Percent Change in Total Brain Volume [From Baseline through 288 weeks]

   To assess brain atrophy, total brain volume was be measured by MRI and analyzed by a central reader.

8. Number of Participants With Antibodies to DAC HYP [Up to Week 288]

9. Annualized Relapse Rate (ARR) [Week 288]

   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 ARR was calculated by tabulating the total number of relapses experienced in the group divided by the number of days up to the end of study, and the ratio then multiplied by 365. Adjusted ARR was reported.

10. Number of Participants With Sustained Disability Progression for 12 Weeks [Week 48 up to Week 288]

    Sustained disability progression defined by at least a 1.0-point increase on the Expanded Disability Status Scale (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. 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.

11. Number of Participants With Sustained Disability Progression for 24 Weeks [Week 48 up to Week 288]

    Sustained disability progression defined by at least a 1.0-point increase on the Expanded Disability Status Scale (EDSS) from a baseline EDSS ≥1.0 that is sustained for 24 weeks, or at least a 1.5-point increase on the EDSS from a baseline EDSS <1.0 that is sustained for 24 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.

12. Observed Maximum Concentration (Cmax) After Dose 4 for Daclizumab [Day 90 (Week 12) at predose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14, 21 and 28 days post-dose]

13. Time to Reach Maximum Concentration (Tmax) for Daclizumab After Dose 4 [Day 90 (Week 12) at predose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14, 21 and 28 days post-dose]

14. Observed Minimum Concentration (Cmin) for Daclizumab After Dose 4 [Day 90 (Week 12) at predose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14, 21 and 28 days post-dose]

15. Participant-Reported Pain Visual Analog Scale (VAS) Score [First injection (Day 1) and fourth injection (Day 90) 0 hour, 30 minutes, 60 minutes and 8 hours post-dose]

    The VAS is a 10 cm-long horizontal line labeled with 2 extremes of pain at either end ("0 [no pain]" on the left and "100 [very painful]" on the right). The participant rates their perceived pain of each injection by placing a vertical mark on the line to indicate the level of pain.

16. Summary of Injection Site Assessment Performed by Clinician [First injection (Day 1) and fourth injection (Day 90) 30 minutes; 8, 24, 72, and 120 hours; and 7, 10, and 14 days post-dose]

    Injection site assessment was performed by clinician and are defined as erythema (redness) rated on a 4 point scale ranging from 0-3, where 0=none, 1=mild, 2=moderate and 3=severe; pigmentation changes (skin discoloration other than redness) rated on a 3 point scale from 0-2, where 0=none, 1=hypopigmentation and 2=hyperpigmentation; induration (swelling) rated on a 4 point scale ranging from 0-3, where 0=none, 1=mild, 2=moderate and 3=severe; tenderness to pressure rated on a 4 point scale ranging from 0-3, where 0=none, 1=mild, 2=moderate and 3=severe; and local temperature changes of injection sites rated on a 3 point scale where 0=normal, 1=warm and 1=hot. Only those score categories for which there was at least 1 participant are reported. Here, Injection=Inj, post-dose=PD

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Main Study Eligibility:

Key Inclusion Criteria:

• 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.

• Subjects who have completed 52 weeks in Study 205MS202 (NCT00870740) and were compliant with the 205MS202 protocol in the opinion of the Investigator.

• 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.

Key Exclusion Criteria:

• Subjects with any significant change in their medical status from the previous study that would prelude administration of Daclizumab High Yield Process (DAC HYP) as determined by the Investigator 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 (NCT00390221) or 205MS202 (NCT00870740) studies. The Investigator must re-review the subject's medical fitness for participation and must consider any diseases that would preclude treatment.

• Any subject who has permanently discontinued study treatment in Study 205MS202 (NCT00870740) due to an adverse event.

• Current enrollment in any investigational drug study other than Study 205MS202 (NCT00870740).

• Ongoing treatment with any approved or experimental disease-modifying treatment for multiple sclerosis.

• 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 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.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Brno		Czechia	625 00
2	Research Site	Brno		Czechia	656 91
3	Research Site	Hradec Kralove		Czechia	500 02
4	Research Site	Prague		Czechia	100 34
5	Research Site	Teplice		Czechia	415 29
6	Research Site	Bayreuth		Germany	95445
7	Research Site	Erlangen		Germany	91054
8	Research Site	Marburg		Germany	35043
9	Research Site	Rostock		Germany	18147
10	Research Site	Budapest		Hungary	1076
11	Research Site	Budapest		Hungary	1083
12	Research Site	Budapest		Hungary	1115
13	Research Site	Budapest		Hungary	1125
14	Research Site	Budapest		Hungary	1134
15	Research Site	Debrecen		Hungary	4032
16	Research Site	Esztergom		Hungary	2500
17	Research Site	Gyor		Hungary	9024
18	Research Site	Kecskemet		Hungary	6000
19	Research Site	Miskolc		Hungary	3526
20	Research Site	Miskolc		Hungary	3533
21	Research Site	Nyiregyhaza		Hungary	4400
22	Research Site	Siofok		Hungary	8600
23	Research Site	Bangalore		India	560034
24	Research Site	Hyderabad		India	500082
25	Research Site	Kolkata		India	700068
26	Research Site	Mumbai		India	400012
27	Research Site	Rajasthan		India	302021
28	Research Site	Bialystok		Poland	15-276
29	Research Site	Bialystok		Poland	15-420
30	Research Site	Gdansk		Poland	80-803
31	Research Site	Katowice		Poland	40-749
32	Research Site	Katowice		Poland	40-752
33	Research Site	Krakow		Poland	31-505
34	Research Site	Lodz		Poland	93-121
35	Research Site	Lublin		Poland	20954
36	Research Site	Warsaw		Poland	02-957
37	Research Site	Warszawa		Poland	02-097
38	Research Site	Kazan		Russian Federation	420021
39	Research Site	Krasnoyarsk		Russian Federation	660049
40	Research Site	Moscow		Russian Federation	107150
41	Research Site	Moscow		Russian Federation	115682
42	Research Site	Moscow		Russian Federation	6127018
43	Research Site	Nizhniy Novgorod		Russian Federation	603076
44	Research Site	Novosibirsk		Russian Federation	630087
45	Research Site	Omsk		Russian Federation	644033
46	Research Site	Samara		Russian Federation	443095
47	Research Site	Smolensk		Russian Federation	214018
48	Research Site	St Petersburg		Russian Federation	194291
49	Research Site	Ufa		Russian Federation	450005
50	Research Site	Yaroskavi		Russian Federation	150030
51	Research Site	Chernivtsi		Ukraine	58018
52	Research Site	Dnipropetrovsk		Ukraine	49027
53	Research Site	Donetsk		Ukraine	83003
54	Research Site	Kharkiv		Ukraine	61068
55	Research Site	Kiev		Ukraine	03110
56	Research Site	Kiev		Ukraine	2125
57	Research Site	Kyiv		Ukraine	03110
58	Research Site	Poltava		Ukraine	36024
59	Research Site	Zaporizhia		Ukraine	69035
60	Research Site	Zaporizhia		Ukraine	69600
61	Research Site	London		United Kingdom	SE59RF
62	Research Site	Nottingham		United Kingdom	NG72UH
63	Research Site	Plymouth		United Kingdom	PL68DH
64	Research Site	Sheffield		United Kingdom	S102JF
65	Research Site	Stoke-on-Trent		United Kingdom	ST47LN

Sponsors and Collaborators

• Biogen
• AbbVie

Investigators

• Study Director: Medical Director, Biogen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• The website of the National Multiple Sclerosis Society, an organization dedicated to providing information to individuals with MS their families and healthcare providers

Publications

None provided.

• Responsible Party: Biogen
• ClinicalTrials.gov Identifier: NCT01051349
• Other Study ID Numbers: 205-MS-203; 2009-015318-23
• First Posted: Jan 18, 2010
• Last Update Posted: Nov 9, 2018
• Last Verified: Apr 1, 2018

• Keywords provided by Biogen: MS; Multiple Sclerosis
• Additional relevant MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis; Daclizumab

Study Results

Participant Flow

Recruitment Details	Out of 410 enrolled participants, 60 participants who received at least 6 consecutive monthly doses of DAC HYP in this study and had provided written informed consent were enrolled in to the autoinjector substudy and 91 participants who received seasonal trivalent influenza vaccine were enrolled in vaccine substudy (exploratory analyses).

Arm/Group Title	BIIB019
Arm/Group Description	Participants received BIIB019, 150 mg subcutaneous injection every 4 weeks up to Week 276.
Period Title: Overall Study
STARTED	410
COMPLETED	237
NOT COMPLETED	173

Baseline Characteristics

Arm/Group Title	BIIB019
Arm/Group Description	Participants received BIIB019, 150 mg subcutaneous injection every 4 weeks up to Week 276.
Overall Participants	410
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.4 (8.74)
Sex: Female, Male (Count of Participants)
Female	254 62%
Male	156 38%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuation Due to AEs, Withdrawals Due to AEs
Description	An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A SAE is any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important due to other reasons than the above mentioned criteria.
Time Frame	Baseline up to 24 weeks after last dose of treatment (Up to 300 weeks)

Outcome Measure Data

Analysis Population Description

Safety population included participants who provided informed consent and received at least 1 dose of DAC HYP during the study.

Arm/Group Title	BIIB019
Arm/Group Description	Participants received BIIB019, 150 mg subcutaneous injection every 4 weeks up to Week 276.
Measure Participants	410
Number of participants with an AEs	358 87.3%
Number of participants with SAEs	148 36.1%
Participants discontinuing treatment due to AE	91 22.2%
Participants withdrawing from study due to AE	90 22%

2. Primary Outcome

Title	Area Under the Concentration-Time Curve Over the Dosing Interval (AUC0-t) After Dose 4 for Daclizumab
Time Frame	Day 90 (Week 12) at predose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14, 21 and 28 days post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis population included all participants in the Autoinjector Substudy with a sufficient number of samples available for analysis by randomized treatment group.

Arm/Group Title	BIIB019 (Prefilled Syringe [PFS])	BIIB019 (Autoinjector [AI])
Arm/Group Description	Participants received BIIB019, 150 mg subcutaneous injection in a prefilled syringe every 4 weeks up to Week 276.	Participants received BIIB019, 150 mg subcutaneous injection using an autoinjector every 4 weeks up to Week 276.
Measure Participants	30	30
Mean (Standard Deviation) [hr*mg/mL]	610.5 (253.89)	666.8 (253.19)

3. Secondary Outcome

Title	Number of Participants With New or Newly Enlarging T2 Hyperintense Lesions Compared to Baseline
Description	New or newly enlarging T2 hyperintense lesions evaluated by magnetic resonance imaging (MRI) and analyzed by a central reader.
Time Frame	From Baseline through 288 weeks

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population included participants who provided informed consent and received at least 1 dose of DAC HYP during the study. Here 'n' indicates number of participants who were evaluable at specific time points.

Arm/Group Title	BIIB019
Arm/Group Description	Participants received BIIB019, 150 mg subcutaneous injection every 4 weeks up to Week 276.
Measure Participants	410
Week 48 New or newly enlarging T2 lesions=0	255 62.2%
Week 48 New or newly enlarging T2 lesions=1	39 9.5%
Week 48 New or newly enlarging T2 lesions=2	27 6.6%
Week 48 New or newly enlarging T2 lesions=3	12 2.9%
Week 48 New or newly enlarging T2 lesions=4	5 1.2%
Week 48 New/newly enlarging T2 lesions=5-6	6 1.5%
Week 48 New/newly enlarging T2 lesions=7-10	8 2%
Week 48 New/newly enlarging T2 lesions>=11	11 2.7%
Week 96 New/newly enlarging T2 lesions=0	213 52%
Week 96 New/newly enlarging T2 lesions=1	41 10%
Week 96 New/newly enlarging T2 lesions=2	17 4.1%
Week 96 New/newly enlarging T2 lesions=3	17 4.1%
Week 96 New/newly enlarging T2 lesions=4	11 2.7%
Week 96 New/newly enlarging T2 lesions=5-6	6 1.5%
Week 96 New/newly enlarging T2 lesions=7-10	10 2.4%
Week 96 New/newly enlarging T2 lesions>=11	18 4.4%
Week 144 New/newly enlarging T2 lesions=0	33 8%
Week 144 New/newly enlarging T2 lesions=1	5 1.2%
Week 144 New/newly enlarging T2 lesions=2	1 0.2%
Week 144 New/newly enlarging T2 lesions=3	2 0.5%
Week 144 New/newly enlarging T2 lesions=4	1 0.2%
Week 144 New/newly enlarging T2 lesions=5-6	4 1%
Week 144 New/newly enlarging T2 lesions=7-10	1 0.2%
Week 144 New/newly enlarging T2 lesions>=11	6 1.5%
Week 192 New/newly enlarging T2 lesions=0	144 35.1%
Week 192 New/newly enlarging T2 lesions=1	30 7.3%
Week 192 New/newly enlarging T2 lesions=2	24 5.9%
Week 192 New/newly enlarging T2 lesions=3	13 3.2%
Week 192 New/newly enlarging T2 lesions=4	9 2.2%
Week 192 Ne/newly enlarging T2 lesions=5-6	11 2.7%
Week 192 New/newly enlarging T2lesions=7-10	11 2.7%
Week 192 New/newly enlarging T2 lesions>=11	20 4.9%
Week 240 New/newly enlarging T2 lesions=0	60 14.6%
Week 240 New/newly enlarging T2 lesions=1	10 2.4%
Week 240 New/newly enlarging T2 lesions=2	14 3.4%
Week 240 New/newly enlarging T2 lesions=3	9 2.2%
Week 240 New/newly enlarging T2 lesions=4	7 1.7%
Week 240 New/newly enlarging T2 lesions=5-6	7 1.7%
Week 240 New/newly enlarging T2lesions=7-10	3 0.7%
Week 240 New/newly enlarging T2 lesions>=11	11 2.7%
Week 288 New/newly enlarging T2 lesions=0	14 3.4%
Week 288 New/newly enlarging T2 lesions=1	1 0.2%
Week 288 New/newly enlarging T2 lesions=2	4 1%
Week 288 New/ newly enlarging T2 lesions=3	1 0.2%
Week 288 New/newly enlarging T2 lesions=4	0 0%
Week 288 New/newly enlarging T2 lesions=5-6	1 0.2%
Week 288 New/newly enlarging T2 lesions=7-10	3 0.7%
Week 288 New/newly enlarging T2 lesions>=11	3 0.7%

4. Secondary Outcome

Title	Annual Change in Volume of New or Newly Enlarging T2 Hyperintense Lesions Compared to Baseline
Description	New or newly enlarging T2 hyperintense lesions evaluated by MRI and analyzed by a central reader.
Time Frame	From Baseline through 288 weeks

Outcome Measure Data

Analysis Population Description

ITT population included participants who provided informed consent and received at least 1 dose of DAC HYP during the study. Here 'n' indicates number of participants who were evaluable at specific time points.

Arm/Group Title	BIIB019
Arm/Group Description	Participants received BIIB019, 150 mg subcutaneous injection every 4 weeks up to Week 276.
Measure Participants	410
Change from Baseline at Week 48	-340.8 (1237.64)
Change from Baseline at Week 96	-237.7 (1382.86)
Change from Baseline at Week 144	38.2 (1825.06)
Change from Baseline at Week 192	-251.2 (2326.41)
Change from Baseline at Week 240	-269.7 (1188.82)
Change from Baseline at Week 288	31.9 (1008.87)

5. Secondary Outcome

Title	Number of Participants With Total Number of New Gadolinium-enhancing Lesions
Description	New Gadolinium-enhancing lesions was evaluated by MRI and analyzed by a central reader.
Time Frame	From Baseline through 288 weeks

Outcome Measure Data

Analysis Population Description

ITT population included participants who provided informed consent and received at least 1 dose of DAC HYP during the study. Here 'n' indicates number of participants who were evaluable at specific time points.

Arm/Group Title	BIIB019
Arm/Group Description	Participants received BIIB019, 150 mg subcutaneous injection every 4 weeks up to Week 276.
Measure Participants	410
Week 48 new Gd-enhancing lesions=1	22 5.4%
Week 48 new Gd-enhancing lesions=2	3 0.7%
Week 48 new Gd-enhancing lesions=3	6 1.5%
Week 48 new Gd-enhancing lesions=>4	11 2.7%
Week 96 new Gd-enhancing lesions=1	14 3.4%
Week 96 new Gd-enhancing lesions=2	7 1.7%
Week 96 new Gd-enhancing lesions=3	4 1%
Week 96 new Gd-enhancing lesions=>4	5 1.2%
Week 144 new Gd-enhancing lesions=1	1 0.2%
Week 144 new Gd-enhancing lesions=2	0 0%
Week 144 new Gd-enhancing lesions=3	1 0.2%
Week 144 new Gd-enhancing lesions=>4	2 0.5%
Week 192 new Gd-enhancing lesions=1	13 3.2%
Week 192 new Gd-enhancing lesions=2	5 1.2%
Week 192 new Gd-enhancing lesions=3	1 0.2%
Week 192 new Gd-enhancing lesions=>4	0 0%
Week 240 new Gd-enhancing lesions=1	5 1.2%
Week 240 new Gd-enhancing lesions=2	0 0%
Week 240 new Gd-enhancing lesions=3	0 0%
Week 240 new Gd-enhancing lesions=>4	0 0%
Week 288 new Gd-enhancing lesions=1	2 0.5%
Week 288 new Gd-enhancing lesions=2	0 0%
Week 288 new Gd-enhancing lesions=3	0 0%
Week 288 new Gd-enhancing lesions=>4	0 0%

6. Secondary Outcome

Title	Annual Change in Number of T1 Hypointense Lesions
Time Frame	From Baseline through 288 weeks

Outcome Measure Data

Analysis Population Description

T1 hypointense lesions changes reflect tissue destruction. Volume of T1 hypointense lesions is deemed a more valuable assessment. Hence number of T1 hypointense lesions were not assessed and reported.

Arm/Group Title	BIIB019
Arm/Group Description	Participants received BIIB019, 150 mg subcutaneous injection every 4 weeks up to Week 276.
Measure Participants	0

7. Secondary Outcome

Title	Annual Change in Volume of New Gadolinium-Enhancing Lesions
Time Frame	From Baseline through 288 weeks

Outcome Measure Data

Analysis Population Description

Gd enhancing lesion volume reflects acute inflammatory activity. The number of Gd lesions is a more valuable outcome measure. Hence the volume of Gd enhancing lesions was not assessed and reported.

Arm/Group Title	BIIB019
Arm/Group Description	Participants received BIIB019, 150 mg subcutaneous injection every 4 weeks up to Week 276.
Measure Participants	0

8. Secondary Outcome

Title	Annual Change in Volume of T1 Hypointense Lesions
Description	Volume of T1 hypointense lesions was evaluated by MRI and analyzed by a central reader.
Time Frame	From Baseline through 288 weeks

Outcome Measure Data

Analysis Population Description

ITT population included participants who provided informed consent and received at least 1 dose of DAC HYP during the study. Here 'n' indicates number of participants who were evaluable at specific time points.

Arm/Group Title	BIIB019
Arm/Group Description	Participants received BIIB019, 150 mg subcutaneous injection every 4 weeks up to Week 276.
Measure Participants	410
Change from Baseline at Week 48	-183.5 (370.66)
Change from Baseline at Week 96	-160.6 (443.78)
Change from Baseline at Week 144	-142.4 (432.57)
Change from Baseline at Week 192	-115.2 (826.84)
Change from Baseline at Week 240	-140.8 (514.38)
Change from Baseline at Week 288	-148.4 (500.07)

9. Secondary Outcome

Title	Percent Change in Total Brain Volume
Description	To assess brain atrophy, total brain volume was be measured by MRI and analyzed by a central reader.
Time Frame	From Baseline through 288 weeks

Outcome Measure Data

Analysis Population Description

ITT population included participants who provided informed consent and received at least 1 dose of DAC HYP during the study. Here 'n' indicates number of participants who were evaluable at specific time points.

Arm/Group Title	BIIB019
Arm/Group Description	Participants received BIIB019, 150 mg subcutaneous injection every 4 weeks up to Week 276.
Measure Participants	410
Change from Week 0 to Week 48	-0.4 (1.00)
Change from Week 48 to Week 96	-0.4 (0.78)
Change from Week 96 to Week 144	-0.2 (1.00)
Change from Week 144 to Week 192	-0.5 (0.59)
Change from Week 192 to Week 240	-0.2 (0.83)
Change from Week 240 to Week 288	0.1 (0.73)

10. Secondary Outcome

Title	Number of Participants With Antibodies to DAC HYP
Time Frame	Up to Week 288

Outcome Measure Data

Analysis Population Description

Safety population included participants who provided informed consent and received at least 1 dose of DAC HYP during the study. Here number of participants analyzed is the participants who were evaluated for this outcome measure.

Arm/Group Title	BIIB019
Arm/Group Description	Participants received BIIB019, 150 mg subcutaneous injection every 4 weeks up to Week 276.
Measure Participants	407
Count of Participants [Participants]	43 10.5%

11. Secondary Outcome

Title	Annualized Relapse Rate (ARR)
Description	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 ARR was calculated by tabulating the total number of relapses experienced in the group divided by the number of days up to the end of study, and the ratio then multiplied by 365. Adjusted ARR was reported.
Time Frame	Week 288

Outcome Measure Data

Analysis Population Description

ITT population included participants who provided informed consent and received at least 1 dose of DAC HYP during the study.

Arm/Group Title	BIIB019
Arm/Group Description	Participants received BIIB019, 150 mg subcutaneous injection every 4 weeks up to Week 276.
Measure Participants	410
Number (95% Confidence Interval) [relapses per person-year]	0.124

12. Secondary Outcome

Title	Number of Participants With Sustained Disability Progression for 12 Weeks
Description	Sustained disability progression defined by at least a 1.0-point increase on the Expanded Disability Status Scale (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. 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.
Time Frame	Week 48 up to Week 288

Outcome Measure Data

Analysis Population Description

ITT population included participants who provided informed consent and received at least 1 dose of DAC HYP during the study.

Arm/Group Title	BIIB019
Arm/Group Description	Participants received BIIB019, 150 mg subcutaneous injection every 4 weeks up to Week 276.
Measure Participants	410
Weeks 0 - 48	22 5.4%
Weeks 49 - 96	17 4.1%
Weeks 97 - 144	13 3.2%
Weeks 145 -192	7 1.7%
Week 193 - 288	2 0.5%

13. Secondary Outcome

Title	Number of Participants With Sustained Disability Progression for 24 Weeks
Description	Sustained disability progression defined by at least a 1.0-point increase on the Expanded Disability Status Scale (EDSS) from a baseline EDSS ≥1.0 that is sustained for 24 weeks, or at least a 1.5-point increase on the EDSS from a baseline EDSS <1.0 that is sustained for 24 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.
Time Frame	Week 48 up to Week 288

Outcome Measure Data

Analysis Population Description

ITT population included participants who provided informed consent and received at least 1 dose of DAC HYP during the study.

Arm/Group Title	BIIB019
Arm/Group Description	Participants received BIIB019, 150 mg subcutaneous injection every 4 weeks up to Week 276.
Measure Participants	410
Weeks 0 - 48	19 4.6%
Weeks 49 - 96	18 4.4%
Weeks 97 - 144	11 2.7%
Weeks 145 -192	7 1.7%
Week 193 - 288	3 0.7%

14. Secondary Outcome

Title	Observed Maximum Concentration (Cmax) After Dose 4 for Daclizumab
Time Frame	Day 90 (Week 12) at predose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14, 21 and 28 days post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis population included all participants with a sufficient number of samples available for analysis.

Arm/Group Title	BIIB019 (Prefilled Syringe [PFS])	BIIB019 (Autoinjector [AI])
Arm/Group Description	Participants received BIIB019, 150 mg subcutaneous injection in a prefilled syringe every 4 weeks up to Week 288.	Participants received BIIB019, 150 mg subcutaneous injection using an autoinjector every 4 weeks up to Week 276.
Measure Participants	30	30
Mean (Standard Deviation) [mg/mL]	31.8 (13.11)	33.6 (14.79)

15. Secondary Outcome

Title	Time to Reach Maximum Concentration (Tmax) for Daclizumab After Dose 4
Time Frame	Day 90 (Week 12) at predose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14, 21 and 28 days post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis population included all participants with a sufficient number of samples available for analysis.

Arm/Group Title	BIIB019 (Prefilled Syringe [PFS])	BIIB019 (Autoinjector [AI])
Arm/Group Description	Participants received BIIB019, 150 mg subcutaneous injection in a prefilled syringe every 4 weeks up to Week 288.	Participants received BIIB019, 150 mg subcutaneous injection using an autoinjector every 4 weeks up to Week 276.
Measure Participants	30	30
Median (Full Range) [hour]	5.0	6.0

16. Secondary Outcome

Title	Observed Minimum Concentration (Cmin) for Daclizumab After Dose 4
Time Frame	Day 90 (Week 12) at predose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14, 21 and 28 days post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic analysis population included all participants with a sufficient number of samples available for analysis.

Arm/Group Title	BIIB019 (Prefilled Syringe [PFS])	BIIB019 (Autoinjector [AI])
Arm/Group Description	Participants received BIIB019, 150 mg subcutaneous injection in a prefilled syringe every 4 weeks up to Week 288.	Participants received BIIB019, 150 mg subcutaneous injection using an autoinjector every 4 weeks up to Week 276.
Measure Participants	30	30
Mean (Standard Deviation) [mg/mL]	13.8 (7.13)	15.7 (7.31)

17. Secondary Outcome

Title	Participant-Reported Pain Visual Analog Scale (VAS) Score
Description	The VAS is a 10 cm-long horizontal line labeled with 2 extremes of pain at either end ("0 [no pain]" on the left and "100 [very painful]" on the right). The participant rates their perceived pain of each injection by placing a vertical mark on the line to indicate the level of pain.
Time Frame	First injection (Day 1) and fourth injection (Day 90) 0 hour, 30 minutes, 60 minutes and 8 hours post-dose

Outcome Measure Data

Analysis Population Description

The participants who were enrolled in auto-injector sub study were evaluated in this outcome measure. Here 'n' indicates number of participants who were evaluable at specific time points.

Arm/Group Title	BIIB019 (Prefilled Syringe [PFS])	BIIB019 (Autoinjector [AI])
Arm/Group Description	Participants received BIIB019, 150 mg subcutaneous injection in a prefilled syringe every 4 weeks up to Week 288.	Participants received BIIB019, 150 mg subcutaneous injection using an autoinjector every 4 weeks up to Week 276.
Measure Participants	30	30
First injection, 0 hour post-dose	12.7 (17.45)	14.5 (19.47)
First injection, 30 minutes post-dose	0.1 (0.31)	0.4 (1.01)
First injection, 60 minutes post-dose	0.1 (0.25)	0.3 (0.60)
First injection, 8 hours post-dose	0.1 (0.25)	0.2 (0.50)
Fourth injection, 0 hour post-dose	14.5 (21.7)	15.6 (24.70)
Fourth injection, 30 minutes post-dose	0.9 (3.51)	1.3 (3.42)
Fourth injection, 60 minutes post-dose	0.0 (0.18)	0.1 (0.31)
Fourth injection, 8 hours post-dose	0.1 (0.40)	0.1 (0.31)

18. Secondary Outcome

Title	Summary of Injection Site Assessment Performed by Clinician
Description	Injection site assessment was performed by clinician and are defined as erythema (redness) rated on a 4 point scale ranging from 0-3, where 0=none, 1=mild, 2=moderate and 3=severe; pigmentation changes (skin discoloration other than redness) rated on a 3 point scale from 0-2, where 0=none, 1=hypopigmentation and 2=hyperpigmentation; induration (swelling) rated on a 4 point scale ranging from 0-3, where 0=none, 1=mild, 2=moderate and 3=severe; tenderness to pressure rated on a 4 point scale ranging from 0-3, where 0=none, 1=mild, 2=moderate and 3=severe; and local temperature changes of injection sites rated on a 3 point scale where 0=normal, 1=warm and 1=hot. Only those score categories for which there was at least 1 participant are reported. Here, Injection=Inj, post-dose=PD
Time Frame	First injection (Day 1) and fourth injection (Day 90) 30 minutes; 8, 24, 72, and 120 hours; and 7, 10, and 14 days post-dose

Outcome Measure Data

Analysis Population Description

The participants who were enrolled in auto-injector sub study were evaluated in this outcome measure. Here 'n' indicates number of participants who were evaluable at specific time points.

Arm/Group Title	BIIB019 (Prefilled Syringe [PFS])	BIIB019 (Autoinjector [AI])
Arm/Group Description	Participants received BIIB019, 150 mg subcutaneous injection in a prefilled syringe every 4 weeks up to Week 288.	Participants received BIIB019, 150 mg subcutaneous injection using an autoinjector every 4 weeks up to Week 276.
Measure Participants	30	30
Erythema: Ist Inj 30 min PD: None	29 7.1%	29 NaN
Erythema:Ist Inj 30 min PD: Mild	1 0.2%	1 NaN
Erythema: Ist Inj 8 h PD: None	30 7.3%	29 NaN
Erythema:Ist Inj 8 h PD: MIld	0 0%	1 NaN
Erythema: Ist Inj 24 h PD: None	28 6.8%	27 NaN
Erythema: Ist Inj 72 h PD: None	26 6.3%	26 NaN
Erythema: Ist Inj 120 h PD: None	26 6.3%	26 NaN
Erythema: Ist Inj 7 days PD: None	26 6.3%	26 NaN
Erythema: Ist Inj 10 days PD: None	26 6.3%	26 NaN
Erythema: Ist Inj 14 days PD: None	26 6.3%	26 NaN
Erythema: 4th Inj 30 min PD: None	30 7.3%	28 NaN
Erythema: 4th Inj 30 min PD: Mild	0 0%	1 NaN
Erythema: 4th Inj 8 h PD: None	30 7.3%	28 NaN
Erythema: 4th Inj 24 h PD: None	30 7.3%	27 NaN
Erythema: 4th Inj 72 h PD: None	29 7.1%	26 NaN
Erythema: 4th Inj 120 h PD: None	30 7.3%	27 NaN
Erythema: 4th Inj 7 days PD: None	30 7.3%	28 NaN
Erythema: 4th Inj 10 days PD: None	30 7.3%	28 NaN
Erythema: 4th Inj 14 days PD: None	30 7.3%	28 NaN
Pigmentation: 1st Inj, 30 min PD: None	30 7.3%	30 NaN
Pigmentation: 1st Inj, 8 h PD: None	30 7.3%	30 NaN
Pigmentation: 1st Inj, 24 h PD: None	28 6.8%	27 NaN
Pigmentation: 1st Inj, 72 h PD: None	26 6.3%	26 NaN
Pigmentation: 1st Inj, 120 h PD: None	26 6.3%	26 NaN
Pigmentation: 1st Inj, 7 days PD: None	26 6.3%	26 NaN
Pigmentation: 1st Inj, 10 days PD: None	26 6.3%	26 NaN
Pigmentation: 1st Inj, 14 days PD: None	26 6.3%	26 NaN
Pigmentation: 4th Inj, 30 min PD: None	30 7.3%	28 NaN
Pigmentation: 4th Inj, 8 h PD: None	30 7.3%	28 NaN
Pigmentation: 4th Inj, 24 h PD: None	30 7.3%	27 NaN
Pigmentation: 4th Inj, 72 h PD: None	28 6.8%	26 NaN
Pigmentation: 4th Inj, 72 h PD: Hyper-	1 0.2%	0 NaN
Pigmentation: 4th Inj, 120 h PD: None	29 7.1%	27 NaN
Pigmentation: 4th Inj, 120 h PD: Hyper-	1 0.2%	0 NaN
Pigmentation: 4th Inj, 7 days PD: None	30 7.3%	28 NaN
Pigmentation: 4th Inj, 10 days PD: None	30 7.3%	28 NaN
Pigmentation: 4th Inj, 14 days PD: None	30 7.3%	28 NaN
Induration: 1st Inj, 30 min PD: None	30 7.3%	30 NaN
Induration: 1st Inj, 8 h PD: None	30 7.3%	30 NaN
Induration: 1st Inj, 24 h PD: None	28 6.8%	27 NaN
Induration: 1st Inj, 72 h PD: None	26 6.3%	26 NaN
Induration: 1st Inj, 120 h PD: None	26 6.3%	26 NaN
Induration: 1st Inj, 7 days PD: None	26 6.3%	26 NaN
Induration: 1st Inj, 10 days PD: None	26 6.3%	26 NaN
Induration: 1st Inj, 14 days PD: None	26 6.3%	26 NaN
Induration: 4th Inj, 30 min PD: None (n=30, 28)	30 7.3%	28 NaN
Induration: 4th Inj, 8 h PD: None	30 7.3%	28 NaN
Induration: 4th Inj, 24 h PD: None	30 7.3%	27 NaN
Induration: 4th Inj, 72 h PD: None	29 7.1%	26 NaN
Induration: 4th Inj, 120 h PD: None	30 7.3%	27 NaN
Induration: 4th Inj, 7 days PD: None	30 7.3%	28 NaN
Induration: 4th Inj, 10 days PD: None	30 7.3%	28 NaN
Induration: 4th Inj, 14 days PD: None	30 7.3%	28 NaN
Tenderness: 1st Inj, 30 min PD: None	30 7.3%	29 NaN
Tenderness: 1st Inj, 30 min PD: Mild	0 0%	1 NaN
Tenderness: 1st Inj, 8 h PD: None	30 7.3%	30 NaN
Tenderness: 1st Inj, 24 h PD: None	28 6.8%	27 NaN
Tenderness: 1st Inj, 72 h PD: None	26 6.3%	26 NaN
Tenderness: 1st Inj, 120 h PD: None	26 6.3%	26 NaN
Tenderness: 1st Inj, 7 days PD: None	26 6.3%	26 NaN
Tenderness: 1st Inj, 10 days PD: None	26 6.3%	26 NaN
Tenderness: 1st Inj, 14 days PD: None	26 6.3%	26 NaN
Tenderness: 4th Inj, 30 min PD: None	30 7.3%	27 NaN
Tenderness: 4th Inj, 30 min PD: Mild	0 0%	1 NaN
Tenderness: 4th Inj, 8 h PD: None	30 7.3%	27 NaN
Tenderness: 4th Inj, 8 h PD: Mild	0 0%	1 NaN
Tenderness: 4th Inj, 24 h PD: None	30 7.3%	27 NaN
Tenderness: 4th Inj, 72 h PD: None	29 7.1%	26 NaN
Tenderness: 4th Inj, 120 h PD: None	30 7.3%	27 NaN
Tenderness: 4th Inj, 7 days PD: None	30 7.3%	28 NaN
Tenderness: 4th Inj, 10 days PD: None	30 7.3%	28 NaN
Tenderness: 4th Inj, 14 days PD: None	30 7.3%	28 NaN
Temperature: 1st Inj, 30 min PD: Normal	30 7.3%	30 NaN
Temperature: 1st Inj, 8 h PD: Normal	30 7.3%	30 NaN
Temperature: 1st Inj, 24 h PD: Normal	28 6.8%	27 NaN
Temperature: 1st Inj, 72 h PD: Normal	26 6.3%	26 NaN
Temperature: 1st Inj, 120 h PD: Normal	26 6.3%	26 NaN
Temperature: 1st Inj, 7 days PD: Normal	26 6.3%	26 NaN
Temperature: 1st Inj,10 days PD: Normal	26 6.3%	26 NaN
Temperature: 1st Inj,14 days PD: Normal	26 6.3%	26 NaN
Temperature: 4th Inj, 30 min PD: Normal	30 7.3%	28 NaN
Temperature: 4th Inj, 8 h PD: Normal	30 7.3%	28 NaN
Temperature: 4th Inj, 24 h PD: Normal	30 7.3%	27 NaN
Temperature: 4th Inj, 72 h PD: Normal	29 7.1%	26 NaN
Temperature: 4th Inj, 120 h PD: Normal	30 7.3%	27 NaN
Temperature: 4th Inj, 7 days PD: Normal	30 7.3%	28 NaN
Temperature: 4th Inj,10 days PD: Normal	30 7.3%	28 NaN
Temperature: 4th Inj,14 days PD: Normal	30 7.3%	28 NaN

Adverse Events

Time Frame	Baseline up to 24 weeks after last dose of treatment (Up to 300 weeks)
Adverse Event Reporting Description	Treatment emergent AEs are presented regardless of seriousness or relationship to investigational product.
Arm/Group Title	BIIB019
Arm/Group Description	Participants received BIIB019, 150 mg subcutaneous injection every 4 weeks up to Week 276.
All Cause Mortality
	BIIB019
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	BIIB019
	Affected / at Risk (%)	# Events
Total	148/410 (36.1%)
Blood and lymphatic system disorders
Febrile neutropenia	1/410 (0.2%)
Haemolytic anaemia	1/410 (0.2%)
Haemorrhagic anaemia	1/410 (0.2%)
Histiocytosis haematophagic	1/410 (0.2%)
Iron deficiency anaemia	1/410 (0.2%)
Lymphadenitis	2/410 (0.5%)
Lymphadenopathy	6/410 (1.5%)
Lymphoid tissue hyperplasia	1/410 (0.2%)
Pancytopenia	1/410 (0.2%)
Thrombocytopenic purpura	1/410 (0.2%)
Cardiac disorders
Myocardial infarction	1/410 (0.2%)
Congenital, familial and genetic disorders
Dermoid cyst	1/410 (0.2%)
Ear and labyrinth disorders
Vertigo	1/410 (0.2%)
Endocrine disorders
Goitre	1/410 (0.2%)
Eye disorders
Choroiditis	1/410 (0.2%)
Gastrointestinal disorders
Abdominal hernia	1/410 (0.2%)
Colitis	1/410 (0.2%)
Colitis ulcerative	3/410 (0.7%)
Crohn's disease	1/410 (0.2%)
Diarrhoea	1/410 (0.2%)
Enterocolitis haemorrhagic	1/410 (0.2%)
Gastritis	2/410 (0.5%)
Ileus	1/410 (0.2%)
Ileus paralytic	1/410 (0.2%)
Lip oedema	1/410 (0.2%)
Obstruction gastric	1/410 (0.2%)
General disorders
Impaired healing	1/410 (0.2%)
Hepatobiliary disorders
Autoimmune hepatitis	2/410 (0.5%)
Cholecystitis acute	1/410 (0.2%)
Cholelithiasis	2/410 (0.5%)
Hepatitis	1/410 (0.2%)
Jaundice hepatocellular	1/410 (0.2%)
Liver disorder	1/410 (0.2%)
Immune system disorders
Anaphylactic reaction	1/410 (0.2%)
Drug hypersensitivity	1/410 (0.2%)
Infections and infestations
Acute sinusitis	1/410 (0.2%)
Appendicitis	1/410 (0.2%)
Bronchitis	2/410 (0.5%)
Clostridium difficile colitis	1/410 (0.2%)
Diverticulitis	1/410 (0.2%)
Erysipelas	1/410 (0.2%)
Furuncle	1/410 (0.2%)
Gastrointestinal infection	1/410 (0.2%)
Hepatitis c	1/410 (0.2%)
Herpes zoster	2/410 (0.5%)
Hiv infection	1/410 (0.2%)
Infectious mononucleosis	1/410 (0.2%)
Peritonsillar abscess	1/410 (0.2%)
Pneumonia	2/410 (0.5%)
Pyelonephritis acute	1/410 (0.2%)
Tonsillitis	1/410 (0.2%)
Upper respiratory tract infection	1/410 (0.2%)
Urinary tract infection	5/410 (1.2%)
Wound infection	2/410 (0.5%)
Injury, poisoning and procedural complications
Cervical vertebral fracture	1/410 (0.2%)
Concussion	2/410 (0.5%)
Foot fracture	2/410 (0.5%)
Lower limb fracture	2/410 (0.5%)
Pubis fracture	1/410 (0.2%)
Road traffic accident	2/410 (0.5%)
Spinal column injury	1/410 (0.2%)
Upper limb fracture	2/410 (0.5%)
Wound	1/410 (0.2%)
Investigations
Alanine aminotransferase increased	1/410 (0.2%)
Aspartate aminotransferase increased	1/410 (0.2%)
Gamma-glutamyltransferase increased	1/410 (0.2%)
Hepatic enzyme increased	2/410 (0.5%)
Liver function test abnormal	1/410 (0.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/410 (0.2%)
Arthritis reactive	1/410 (0.2%)
Back pain	1/410 (0.2%)
Intervertebral disc disorder	2/410 (0.5%)
Osteoarthritis	1/410 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anal cancer	1/410 (0.2%)
Benign neoplasm of bladder	1/410 (0.2%)
Breast cancer	3/410 (0.7%)
Carcinoid tumour pulmonary	1/410 (0.2%)
Clear cell renal cell carcinoma	1/410 (0.2%)
Intraductal papilloma of breast	1/410 (0.2%)
Prolactinoma	1/410 (0.2%)
T-cell lymphoma	1/410 (0.2%)
Uterine leiomyoma	1/410 (0.2%)
Nervous system disorders
Grand mal convulsion	1/410 (0.2%)
Headache	1/410 (0.2%)
Ischaemic stroke	1/410 (0.2%)
Multiple sclerosis	1/410 (0.2%)
Multiple sclerosis relapse	62/410 (15.1%)
Neurological decompensation	1/410 (0.2%)
Vascular encephalopathy	1/410 (0.2%)
Pregnancy, puerperium and perinatal conditions
Ectopic pregnancy	1/410 (0.2%)
Psychiatric disorders
Depression	1/410 (0.2%)
Suicide attempt	1/410 (0.2%)
Renal and urinary disorders
Glomerulonephritis	1/410 (0.2%)
Haematuria	1/410 (0.2%)
Nephroptosis	1/410 (0.2%)
Renal colic	1/410 (0.2%)
Reproductive system and breast disorders
Adenomyosis	1/410 (0.2%)
Ovarian cyst	1/410 (0.2%)
Postmenopausal haemorrhage	1/410 (0.2%)
Uterine inflammation	1/410 (0.2%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/410 (0.2%)
Idiopathic pulmonary fibrosis	1/410 (0.2%)
Interstitial lung disease	1/410 (0.2%)
Skin and subcutaneous tissue disorders
Angioedema	1/410 (0.2%)
Dermatitis	1/410 (0.2%)
Dermatitis allergic	2/410 (0.5%)
Drug eruption	1/410 (0.2%)
Eczema	1/410 (0.2%)
Erythema nodosum	1/410 (0.2%)
Erythrodermic psoriasis	1/410 (0.2%)
Photodermatosis	1/410 (0.2%)
Psoriasis	2/410 (0.5%)
Seborrhoeic dermatitis	1/410 (0.2%)
Stevens-johnson syndrome	1/410 (0.2%)
Toxic skin eruption	3/410 (0.7%)
Urticaria	3/410 (0.7%)
Surgical and medical procedures
Drug detoxification	1/410 (0.2%)
Eyelid operation	1/410 (0.2%)
Mammoplasty	1/410 (0.2%)
Other (Not Including Serious) Adverse Events
	BIIB019
	Affected / at Risk (%)	# Events
Total	296/410 (72.2%)
Blood and lymphatic system disorders
Lymphadenopathy	23/410 (5.6%)
Gastrointestinal disorders
Diarrhoea	25/410 (6.1%)
Infections and infestations
Bronchitis	28/410 (6.8%)
Nasopharyngitis	68/410 (16.6%)
Pharyngitis	42/410 (10.2%)
Respiratory tract infection viral	35/410 (8.5%)
Upper respiratory tract infection	60/410 (14.6%)
Urinary tract infection	42/410 (10.2%)
Viral infection	23/410 (5.6%)
Injury, poisoning and procedural complications
Fall	21/410 (5.1%)
Investigations
Alanine aminotransferase increased	61/410 (14.9%)
Aspartate aminotransferase increased	49/410 (12%)
Musculoskeletal and connective tissue disorders
Arthralgia	21/410 (5.1%)
Back pain	39/410 (9.5%)
Nervous system disorders
Headache	44/410 (10.7%)
Multiple sclerosis relapse	110/410 (26.8%)
Skin and subcutaneous tissue disorders
Dermatitis allergic	32/410 (7.8%)
Rash	31/410 (7.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.