Safety and Efficacy Extension Study of Daclizumab High Yield Process (DAC HYP) in Participants With Multiple Sclerosis Who Have Completed Study 205MS201 (NCT00390221) to Treat Relapsing-Remitting Multiple Sclerosis

A Double-Blind, Multicenter, Extension Study to Evaluate the Safety and Efficacy of DAC HYP in Subjects With Multiple Sclerosis Who Have Completed Treatment in Study 205MS201 (SELECT)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00870740

Acronym

SELECTION

Enrollment

517

Registered

2009-03-27

Start date

2009-02-28

Completion date

2012-10-31

Last updated

2016-08-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Relapsing-Remitting Multiple Sclerosis

Keywords

MS, Multiple Sclerosis

Brief summary

The primary objective of the study was to assess the safety and immunogenicity of extended treatment with DAC HYP. This evaluation included the following major components: * An assessment of safety and immunogenicity of extended treatment with DAC HYP when administered to MS subjects who had completed 52 weeks of active therapy with DAC HYP in Study 201. * An assessment of safety and immunogenicity during a 6-month washout period from DAC HYP. * An assessment of safety and immunogenicity during reinitiation of therapy with DAC HYP after a 6-month washout period. * An assessment of safety and immunogenicity of DAC HYP when administered to MS subjects who previously received placebo during Study 201. The secondary objective is to assess the durability of the effect of DAC HYP on multiple sclerosis (MS) disease activity as measured by brain magnetic resonance imaging (MRI) scans and clinical MS relapses.

Detailed description

This study, an extension to Study 205MS201 (NCT00390221), will evaluate the long-term safety, efficacy, and immunogenicity of DAC HYP in MS. In Study 205MS201, study treatment was scheduled to stop at the Week 52 visit. This extension study will provide for the initiation of active therapy with DAC HYP among participants who received placebo during Weeks 0 through 52 in 205MS201. In addition, participants who received active therapy with DAC HYP during Weeks 0 through 52 in Study 205MS201 will continue DAC HYP therapy or resume DAC HYP therapy after a 6-month washout period in this study.

Interventions

BIOLOGICALBIIB019 (Daclizumab High Yield Process)

SC injection

DRUGPlacebo

Placebo SC injection

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Inclusion criteria

Key Inclusion Criteria: * Participated in Study 205MS201 (NCT00390221) for at least 52 weeks and was compliant with the 205MS201 protocol in the opinion of the Investigator. Key

Exclusion criteria

* Subjects with any significant change in their medical status from 205MS201 that would preclude administration of DAC HYP, as determined by the Investigator * Any subject who has permanently discontinued study treatment in Study 205MS201 except subjects who were unblinded during evaluation of an adverse event (AE) and found to be on placebo * Planned ongoing treatment with any approved or experimental treatment for MS except for the protocol-allowed use of concomitant interferon-beta NOTE: Other protocol defined Inclusion/

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Treatment-emergent Adverse Events (AEs)	Up to 72 weeks	Treatment-emergent AE: any untoward medical occurrence after the first dose of study treatment that did not necessarily have a causal relationship with this treatment. Serious AE (SAE): any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigator, placed the subject at immediate risk of death (a life-threatening event); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect. An SAE could also have been a medically significant event that, in the opinion of the Investigator, jeopardized the subject or required intervention to prevent one of the other outcomes listed in the definition above.
Number of Participants With Abnormalities in Vital Signs	Up to Week 72	For participants who took DAC HYP during 205MS201 (NCT00390221) the baseline is defined as the baseline from 205MS201, and for participants who took placebo during 205MS201 the baseline is defined as the baseline from 205MS202 (NCT00870740). All post-baseline data are taken after first dose in 205MS202 only. SBP=systolic blood pressure; DBP=diastolic blood pressure; bpm=beats per minute; ↑ BL=increase from baseline; ↓ BL=decrease from baseline.
Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Up to 72 Weeks	Hematology parameters evaluated include: white blood cells, lymphocytes, neutrophils, red blood cells (RBC), hemoglobin, and platelets.
Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Up to 72 Weeks	For each abnormality a subject can be counted once. If a subject has more than one occurrence of the same abnormality the highest toxicity grade is counted. ALT=alanine aminotransferase; AST=aspartate aminotransferase; ALP=alkaline phosphatase; GGT=gamma-glutamyl transferase; TSH=thyroid stimulating hormone, ULN=upper limit of normal.
Number of Participants With Development of Anti-DAC Antibodies (ADAb) and Neutralizing Antibodies (NAb) Post-baseline	Up to 72 weeks	Number of participants positive and negative for ADAb and NAb, based on all post-baseline immunogenicity assessments during treatment period and follow-up. Participants are stratified differently in this Outcome Measure as per the pre-specified statistical analysis plan.

Secondary

Measure	Time frame	Description
Mean Percentage Change From Baseline in Total Lesion Volume of T2 Hyperintense Lesions	Baseline, Week 52	Lesions detected on T2-weighted sequences represent a range of histopathology related to MS, including edema, inflammation, demyelination, gliosis, and axon loss. Evaluated by MRI by a central reader. Baseline values = baseline for study 205MS202 (NCT00870740). For post-baseline visits, the total volume of T2 lesions may be imputed using the mean value across all subjects within the treatment group. Baseline visits are not imputed.
Adjusted Annualized Relapse Rate	Up to 72 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 Independent Neurology Evaluation Committee (INEC). Relapse rate is calculated as: (Total number of relapses that occurred during the 205MS202 \[NCT00870740\] treatment phase divided by the total number of days followed in the treatment phase for 205MS202), multiplied by 365 days. Participants who received an alternative multiple sclerosis (MS) medication during 205MS201 (NCT00390221; Year 1) are not included in the summary of relapses and relapse rate for this study (Year 2). Participants are stratified differently in this Outcome Measure as per the pre-specified statistical analysis plan.
Rate of Percentage Change From Baseline in Mean Total Brain Volume	Baseline, Week 52	Total brain volume was measured by MRI and analyzed by a central reader. Rate of percentage change from baseline calculated using an analysis of covariance adjusting for baseline normalized brain volume. Baseline values = baseline for study 205MS202 (NCT00870740). Missing values post-baseline were imputed using the average value across subjects in the treatment group.
Mean Percentage Change From Baseline in Total Volume of Non-gadolinium (Gd)-Enhancing T1 Hypointense Lesions	Baseline, Week 52	T1-weighted scans detect areas of hypointensity that represent a greater degree of tissue destruction and axon loss than T2 hyperintense lesions and are more highly correlated with clinical disability measures and neurological deficit. Evaluated by MRI by a central reader. Baseline values = baseline for study 205MS202 (NCT00870740). For post-baseline visits, the total volume of T1 lesions may be imputed using the mean value across all participants within the treatment group. Baseline visits are not imputed.
Estimated Proportion of Participants With a Relapse	Up to 72 weeks	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 INEC. Estimated using Kaplan-Meier analysis where time to first relapse is calculated from date of first dose in the study to date of first confirmed relapse. Participants who received an alternative MS medication before the first relapse were censored at the time of taking the alternative MS medication.
Mean Number of New Gadolinium-enhancing Lesions	Week 20, Week 52	Evaluated by magnetic resonance imaging (MRI) by a central reader. Number of new Gd lesions since the previous scan (the previous scan for Week 20 was Week 52 of study 205MS201 \[NCT00390221\]). The number of Gd lesions may be imputed using last observation carried forward or using the mean value across all subjects within the treatment group. Baseline visits are not imputed. Participants are stratified differently in this Outcome Measure as per the pre-specified statistical analysis plan.
Mean Number of New or Newly-enlarging T2 Hyperintense Lesions	Baseline, Week 20, Week 52	Lesions detected on T2-weighted sequences represent a range of histopathology related to MS, including edema, inflammation, demyelination, gliosis, and axon loss. Evaluated by MRI by a central reader. New or newly enlarging T2 lesions since baseline of study 205MS202 (NCT00870740). For post-baseline visits, the number of T2 lesions may be imputed using the mean value across all participants within the treatment group, if the participant has non-missing baseline data. Baseline visits are not imputed. Participants are stratified differently in this Outcome Measure as per the pre-specified statistical analysis plan.
Mean Volume of New T1 Hypointense Lesions	Baseline, Week 20, Week 52	T1-weighted scans detect areas of hypointensity that represent a greater degree of tissue destruction and axon loss than T2 hyperintense lesions and are more highly correlated with clinical disability measures and neurological deficit. Evaluated by MRI by a central reader. Baseline is volume of new T1 hypointense lesions since baseline in study 205MS201 (NCT00390221). Scans at Week 20 and Week 52 in 205MS202 are relative to baseline in 205MS202 (NCT00870740). For post-baseline visits, the total volume of T1 lesions may be imputed using the mean value across all subjects within the treatment group. Baseline visits are not imputed.

Countries

Czechia, Germany, Hungary, India, Poland, Russia, Ukraine, United Kingdom

Participant flow

Participants by arm

Arm	Count
Placebo + DAC HYP 150 mg Participants who previously received placebo in study 205MS201 (NCT00390221) received DAC HYP 150 mg subcutaneous (SC) injection every 4 weeks for a total of 13 doses.	86
Placebo + DAC HYP 300 mg Participants who previously received placebo in study 205MS201 received DAC HYP 300 mg SC injection every 4 weeks for a total of 13 doses.	84
DAC HYP 150 mg + Washout Participants who previously received DAC HYP 150 mg SC injection in study 205MS201 underwent a washout period (placebo SC every 4 weeks for a total of 5 doses) and then received DAC HYP 150 mg SC every 4 weeks for a total of 8 doses.	86
DAC HYP 150 mg for 2 Years Participants who previously received DAC HYP 150 mg SC injection in study 205MS201 received DAC HYP 150 mg SC every 4 weeks for a total of 13 doses.	86
DAC HYP 300 mg + Washout Participants who previously received DAC HYP 300 mg SC in study 205MS201 underwent a washout period (placebo SC every 4 weeks for a total of 5 doses) and then received DAC HYP 300 mg SC every 4 weeks for a total of 8 doses.	88
DAC HYP 300 mg for 2 Years Participants who previously received DAC HYP 300 mg SC in study 205MS201 received DAC HYP 300 mg SC every 4 weeks for a total of 13 doses.	87
Total	517

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005
Overall Study	Adverse Event	2	1	3	2	1	6
Overall Study	Consent Withdrawn	6	3	4	6	6	5
Overall Study	Death	0	0	0	0	1	0
Overall Study	Investigator Decision	2	0	1	0	0	0
Overall Study	Other	2	5	2	4	3	5
Overall Study	Subject Non-compliance	0	0	0	0	0	1

Baseline characteristics

Characteristic	Placebo + DAC HYP 150 mg	Placebo + DAC HYP 300 mg	DAC HYP 150 mg + Washout	DAC HYP 150 mg for 2 Years	DAC HYP 300 mg + Washout	DAC HYP 300 mg for 2 Years	Total
Age, Continuous	38.2 years STANDARD_DEVIATION 9.78	37.8 years STANDARD_DEVIATION 7.98	36.8 years STANDARD_DEVIATION 8.76	36.2 years STANDARD_DEVIATION 9.3	36.2 years STANDARD_DEVIATION 9.03	36.0 years STANDARD_DEVIATION 7.6	36.9 years STANDARD_DEVIATION 8.77
Age, Customized 18 to 19 years	0 participants	0 participants	0 participants	0 participants	1 participants	1 participants	2 participants
Age, Customized 20 to 29 years	19 participants	13 participants	19 participants	25 participants	20 participants	16 participants	112 participants
Age, Customized 30 to 39 years	26 participants	37 participants	29 participants	28 participants	35 participants	41 participants	196 participants
Age, Customized 40 to 49 years	29 participants	28 participants	33 participants	27 participants	24 participants	25 participants	166 participants
Age, Customized 50 to 55 years	11 participants	6 participants	5 participants	6 participants	7 participants	3 participants	38 participants
Age, Customized > 55 years	1 participants	0 participants	0 participants	0 participants	1 participants	1 participants	3 participants
Sex: Female, Male Female	53 Participants	54 Participants	59 Participants	53 Participants	59 Participants	48 Participants	326 Participants
Sex: Female, Male Male	33 Participants	30 Participants	27 Participants	33 Participants	29 Participants	39 Participants	191 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	43 / 86	37 / 84	47 / 86	38 / 86	45 / 88	43 / 87
serious Total, serious adverse events	15 / 86	11 / 84	18 / 86	15 / 86	14 / 88	11 / 87

Outcome results

Primary

Number of Participants With Abnormalities in Blood Chemistry Laboratory Data

For each abnormality a subject can be counted once. If a subject has more than one occurrence of the same abnormality the highest toxicity grade is counted. ALT=alanine aminotransferase; AST=aspartate aminotransferase; ALP=alkaline phosphatase; GGT=gamma-glutamyl transferase; TSH=thyroid stimulating hormone, ULN=upper limit of normal.

Time frame: Up to 72 Weeks

Population: Safety Population: all randomized participants who received study treatment; n=number of participants whose baseline value for 205MS202 (NCT00870740) was normal (i.e. not high or low) and who had at least one post-baseline value during the study.

Arm	Measure	Group	Value (NUMBER)
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP >5 to 20 ULN; n=84,84,84,84,86,86	0 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP >2.5 to 5 ULN; n=84,84,84,84,86,86	0 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST >20 ULN; n=85,81,81,84,85,84	0 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	TSH-3rd Gen Abnormal; n=79,79,74,77,79,79	2 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP >1 to 2.5 ULN; n=84,84,84,84,86,86	8 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP ≤ULN; n=84,84,84,84,86,86	76 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT 3 to 5 ULN; n=84,81,78,81,83,79	0 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin >10 ULN; n=81,79,83,81,85,80	0 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT >5 to 10 ULN; n=84,81,78,81,83,79	1 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Thyroxine (T4) Abnormal; n=76,80,74,72,80,79	3 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin >3 to 10 ULN; n=81,79,83,81,85,80	0 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin >1.5 to 3 ULN; n=81,79,83,81,85,80	2 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT >10 to 20 ULN; n=84,81,78,81,83,79	0 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin >1 to 1.5 ULN; n=81,79,83,81,85,80	5 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT >20 ULN; n=84,81,78,81,83,79	0 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT >1 to <3 ULN; n=84,81,78,81,83,79	18 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin ≤ULN; n=81,79,83,81,85,80	74 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT >20 ULN; n=81,79,81,82,84,82	0 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST ≤ULN; n=85,81,81,84,85,84	72 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT >5 to 20 ULN; n=81,79,81,82,84,82	0 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST >1 to <3 ULN; n=85,81,81,84,85,84	13 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT ≤ULN; n=84,81,78,81,83,79	65 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT >2.5 to 5 ULN; n=81,79,81,82,84,82	2 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT >1 to 2.5 ULN; n=81,79,81,82,84,82	5 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST 3 to 5 ULN; n=85,81,81,84,85,84	0 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT ≤ULN; n=81,79,81,82,84,82	74 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST >5 to 10 ULN; n=85,81,81,84,85,84	0 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Free Thyroxine (T4) Abnormal; n=78,80,73,73,80,79	4 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP >20 ULN; n=84,84,84,84,86,86	0 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST >10 to 20 ULN; n=85,81,81,84,85,84	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT ≤ULN; n=81,79,81,82,84,82	71 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST >10 to 20 ULN; n=85,81,81,84,85,84	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	TSH-3rd Gen Abnormal; n=79,79,74,77,79,79	1 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP >2.5 to 5 ULN; n=84,84,84,84,86,86	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT >20 ULN; n=84,81,78,81,83,79	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP >1 to 2.5 ULN; n=84,84,84,84,86,86	1 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST >5 to 10 ULN; n=85,81,81,84,85,84	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST >20 ULN; n=85,81,81,84,85,84	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT >1 to 2.5 ULN; n=81,79,81,82,84,82	8 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT >20 ULN; n=81,79,81,82,84,82	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP ≤ULN; n=84,84,84,84,86,86	83 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP >20 ULN; n=84,84,84,84,86,86	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP >5 to 20 ULN; n=84,84,84,84,86,86	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT 3 to 5 ULN; n=84,81,78,81,83,79	1 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Thyroxine (T4) Abnormal; n=76,80,74,72,80,79	10 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin >10 ULN; n=81,79,83,81,85,80	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST ≤ULN; n=85,81,81,84,85,84	66 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin >3 to 10 ULN; n=81,79,83,81,85,80	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT >1 to <3 ULN; n=84,81,78,81,83,79	17 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT >5 to 10 ULN; n=84,81,78,81,83,79	1 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT >5 to 20 ULN; n=81,79,81,82,84,82	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST 3 to 5 ULN; n=85,81,81,84,85,84	1 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin >1.5 to 3 ULN; n=81,79,83,81,85,80	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT >2.5 to 5 ULN; n=81,79,81,82,84,82	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT ≤ULN; n=84,81,78,81,83,79	62 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT >10 to 20 ULN; n=84,81,78,81,83,79	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Free Thyroxine (T4) Abnormal; n=78,80,73,73,80,79	4 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin >1 to 1.5 ULN; n=81,79,83,81,85,80	6 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST >1 to <3 ULN; n=85,81,81,84,85,84	14 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin ≤ULN; n=81,79,83,81,85,80	73 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST >1 to <3 ULN; n=85,81,81,84,85,84	9 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT ≤ULN; n=84,81,78,81,83,79	61 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT >1 to <3 ULN; n=84,81,78,81,83,79	16 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT 3 to 5 ULN; n=84,81,78,81,83,79	0 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT >5 to 10 ULN; n=84,81,78,81,83,79	1 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT >10 to 20 ULN; n=84,81,78,81,83,79	0 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT >20 ULN; n=84,81,78,81,83,79	0 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST ≤ULN; n=85,81,81,84,85,84	71 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST 3 to 5 ULN; n=85,81,81,84,85,84	1 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST >5 to 10 ULN; n=85,81,81,84,85,84	0 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST >10 to 20 ULN; n=85,81,81,84,85,84	0 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST >20 ULN; n=85,81,81,84,85,84	0 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP ≤ULN; n=84,84,84,84,86,86	80 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP >1 to 2.5 ULN; n=84,84,84,84,86,86	4 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP >2.5 to 5 ULN; n=84,84,84,84,86,86	0 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP >5 to 20 ULN; n=84,84,84,84,86,86	0 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP >20 ULN; n=84,84,84,84,86,86	0 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT ≤ULN; n=81,79,81,82,84,82	74 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT >1 to 2.5 ULN; n=81,79,81,82,84,82	5 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT >2.5 to 5 ULN; n=81,79,81,82,84,82	2 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT >5 to 20 ULN; n=81,79,81,82,84,82	0 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT >20 ULN; n=81,79,81,82,84,82	0 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin ≤ULN; n=81,79,83,81,85,80	81 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin >1 to 1.5 ULN; n=81,79,83,81,85,80	2 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin >1.5 to 3 ULN; n=81,79,83,81,85,80	0 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin >3 to 10 ULN; n=81,79,83,81,85,80	0 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin >10 ULN; n=81,79,83,81,85,80	0 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	TSH-3rd Gen Abnormal; n=79,79,74,77,79,79	2 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Free Thyroxine (T4) Abnormal; n=78,80,73,73,80,79	5 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Thyroxine (T4) Abnormal; n=76,80,74,72,80,79	6 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	TSH-3rd Gen Abnormal; n=79,79,74,77,79,79	2 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST ≤ULN; n=85,81,81,84,85,84	63 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST >10 to 20 ULN; n=85,81,81,84,85,84	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT >5 to 20 ULN; n=81,79,81,82,84,82	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP >2.5 to 5 ULN; n=84,84,84,84,86,86	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT >5 to 10 ULN; n=84,81,78,81,83,79	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin >1.5 to 3 ULN; n=81,79,83,81,85,80	1 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST 3 to 5 ULN; n=85,81,81,84,85,84	1 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Free Thyroxine (T4) Abnormal; n=78,80,73,73,80,79	4 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT >20 ULN; n=81,79,81,82,84,82	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP >1 to 2.5 ULN; n=84,84,84,84,86,86	4 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin >1 to 1.5 ULN; n=81,79,83,81,85,80	4 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT >20 ULN; n=84,81,78,81,83,79	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT >10 to 20 ULN; n=84,81,78,81,83,79	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT ≤ULN; n=81,79,81,82,84,82	74 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin ≤ULN; n=81,79,83,81,85,80	76 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST >5 to 10 ULN; n=85,81,81,84,85,84	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST >20 ULN; n=85,81,81,84,85,84	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP ≤ULN; n=84,84,84,84,86,86	80 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Thyroxine (T4) Abnormal; n=76,80,74,72,80,79	4 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT >1 to <3 ULN; n=84,81,78,81,83,79	19 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT >1 to 2.5 ULN; n=81,79,81,82,84,82	6 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP >5 to 20 ULN; n=84,84,84,84,86,86	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin >10 ULN; n=81,79,83,81,85,80	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST >1 to <3 ULN; n=85,81,81,84,85,84	20 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT 3 to 5 ULN; n=84,81,78,81,83,79	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin >3 to 10 ULN; n=81,79,83,81,85,80	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT >2.5 to 5 ULN; n=81,79,81,82,84,82	2 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP >20 ULN; n=84,84,84,84,86,86	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT ≤ULN; n=84,81,78,81,83,79	62 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT ≤ULN; n=84,81,78,81,83,79	60 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST >5 to 10 ULN; n=85,81,81,84,85,84	0 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP >5 to 20 ULN; n=84,84,84,84,86,86	0 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	TSH-3rd Gen Abnormal; n=79,79,74,77,79,79	2 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP >20 ULN; n=84,84,84,84,86,86	0 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST 3 to 5 ULN; n=85,81,81,84,85,84	2 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT ≤ULN; n=81,79,81,82,84,82	73 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST >1 to <3 ULN; n=85,81,81,84,85,84	14 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT >1 to 2.5 ULN; n=81,79,81,82,84,82	8 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT >2.5 to 5 ULN; n=81,79,81,82,84,82	2 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST ≤ULN; n=85,81,81,84,85,84	68 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Thyroxine (T4) Abnormal; n=76,80,74,72,80,79	9 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT >5 to 20 ULN; n=81,79,81,82,84,82	1 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT >20 ULN; n=84,81,78,81,83,79	0 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT >20 ULN; n=81,79,81,82,84,82	0 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Free Thyroxine (T4) Abnormal; n=78,80,73,73,80,79	4 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin ≤ULN; n=81,79,83,81,85,80	78 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT >10 to 20 ULN; n=84,81,78,81,83,79	1 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin >1 to 1.5 ULN; n=81,79,83,81,85,80	4 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT >5 to 10 ULN; n=84,81,78,81,83,79	2 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin >1.5 to 3 ULN; n=81,79,83,81,85,80	2 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin >3 to 10 ULN; n=81,79,83,81,85,80	0 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT 3 to 5 ULN; n=84,81,78,81,83,79	0 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin >10 ULN; n=81,79,83,81,85,80	1 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST >20 ULN; n=85,81,81,84,85,84	1 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP ≤ULN; n=84,84,84,84,86,86	81 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT >1 to <3 ULN; n=84,81,78,81,83,79	20 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP >1 to 2.5 ULN; n=84,84,84,84,86,86	5 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST >10 to 20 ULN; n=85,81,81,84,85,84	0 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP >2.5 to 5 ULN; n=84,84,84,84,86,86	0 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT >5 to 20 ULN; n=81,79,81,82,84,82	0 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT 3 to 5 ULN; n=84,81,78,81,83,79	3 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT >2.5 to 5 ULN; n=81,79,81,82,84,82	0 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT ≤ULN; n=84,81,78,81,83,79	55 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	TSH-3rd Gen Abnormal; n=79,79,74,77,79,79	2 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin >3 to 10 ULN; n=81,79,83,81,85,80	0 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP >5 to 20 ULN; n=84,84,84,84,86,86	0 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST ≤ULN; n=85,81,81,84,85,84	62 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Thyroxine (T4) Abnormal; n=76,80,74,72,80,79	9 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT >1 to 2.5 ULN; n=81,79,81,82,84,82	9 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP >1 to 2.5 ULN; n=84,84,84,84,86,86	4 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin >10 ULN; n=81,79,83,81,85,80	0 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST >20 ULN; n=85,81,81,84,85,84	0 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP >2.5 to 5 ULN; n=84,84,84,84,86,86	0 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT >1 to <3 ULN; n=84,81,78,81,83,79	20 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST >1 to <3 ULN; n=85,81,81,84,85,84	18 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP >20 ULN; n=84,84,84,84,86,86	0 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin ≤ULN; n=81,79,83,81,85,80	75 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALP ≤ULN; n=84,84,84,84,86,86	82 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT >10 to 20 ULN; n=84,81,78,81,83,79	1 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Free Thyroxine (T4) Abnormal; n=78,80,73,73,80,79	3 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT >20 ULN; n=81,79,81,82,84,82	0 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	GGT ≤ULN; n=81,79,81,82,84,82	73 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin >1 to 1.5 ULN; n=81,79,83,81,85,80	5 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT >5 to 10 ULN; n=84,81,78,81,83,79	0 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST >10 to 20 ULN; n=85,81,81,84,85,84	0 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST >5 to 10 ULN; n=85,81,81,84,85,84	2 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	ALT >20 ULN; n=84,81,78,81,83,79	0 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	AST 3 to 5 ULN; n=85,81,81,84,85,84	2 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Blood Chemistry Laboratory Data	Total Bilirubin >1.5 to 3 ULN; n=81,79,83,81,85,80	0 participants

Primary

Number of Participants With Abnormalities in Vital Signs

For participants who took DAC HYP during 205MS201 (NCT00390221) the baseline is defined as the baseline from 205MS201, and for participants who took placebo during 205MS201 the baseline is defined as the baseline from 205MS202 (NCT00870740). All post-baseline data are taken after first dose in 205MS202 only. SBP=systolic blood pressure; DBP=diastolic blood pressure; bpm=beats per minute; ↑ BL=increase from baseline; ↓ BL=decrease from baseline.

Time frame: Up to Week 72

Population: Safety population: all randomized participants who received study treatment; n=number of subjects who had a baseline assessment and at least one post-baseline assessment for that vital sign.

Arm	Measure	Group	Value (NUMBER)
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Vital Signs	SBP >180 mmHg w/>40 mmHg ↑ BL; n=86,84,85,85,88,87	0 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Vital Signs	Pulse >120 bpm w/>20 bpm ↑ BL; n=86,84,85,85,88,87	0 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Vital Signs	SBP <90 mmHg w/>30 mmHg ↓ BL; n=86,84,85,85,88,87	1 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Vital Signs	Temperature >38C w/≥1C ↑ BL; n=86,84,85,84,88,87	0 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Vital Signs	DBP >120 mmHg w/>20 mmHg ↑ BL; n=86,84,85,85,88,87	0 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Vital Signs	Pulse <50 bpm w/>20 bpm ↓ BL; n=86,84,85,85,88,87	0 participants
Placebo + DAC HYP 150 mg	Number of Participants With Abnormalities in Vital Signs	DBP <50 mmHg w/>20 mmHg ↓ BL; n=86,84,85,85,88,87	1 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Vital Signs	SBP <90 mmHg w/>30 mmHg ↓ BL; n=86,84,85,85,88,87	1 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Vital Signs	DBP <50 mmHg w/>20 mmHg ↓ BL; n=86,84,85,85,88,87	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Vital Signs	DBP >120 mmHg w/>20 mmHg ↑ BL; n=86,84,85,85,88,87	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Vital Signs	Pulse >120 bpm w/>20 bpm ↑ BL; n=86,84,85,85,88,87	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Vital Signs	SBP >180 mmHg w/>40 mmHg ↑ BL; n=86,84,85,85,88,87	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Vital Signs	Temperature >38C w/≥1C ↑ BL; n=86,84,85,84,88,87	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Abnormalities in Vital Signs	Pulse <50 bpm w/>20 bpm ↓ BL; n=86,84,85,85,88,87	1 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Vital Signs	DBP >120 mmHg w/>20 mmHg ↑ BL; n=86,84,85,85,88,87	0 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Vital Signs	SBP <90 mmHg w/>30 mmHg ↓ BL; n=86,84,85,85,88,87	0 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Vital Signs	SBP >180 mmHg w/>40 mmHg ↑ BL; n=86,84,85,85,88,87	0 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Vital Signs	Pulse >120 bpm w/>20 bpm ↑ BL; n=86,84,85,85,88,87	0 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Vital Signs	Pulse <50 bpm w/>20 bpm ↓ BL; n=86,84,85,85,88,87	1 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Vital Signs	DBP <50 mmHg w/>20 mmHg ↓ BL; n=86,84,85,85,88,87	0 participants
DAC HYP 150 mg + Washout	Number of Participants With Abnormalities in Vital Signs	Temperature >38C w/≥1C ↑ BL; n=86,84,85,84,88,87	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Vital Signs	DBP <50 mmHg w/>20 mmHg ↓ BL; n=86,84,85,85,88,87	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Vital Signs	SBP >180 mmHg w/>40 mmHg ↑ BL; n=86,84,85,85,88,87	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Vital Signs	SBP <90 mmHg w/>30 mmHg ↓ BL; n=86,84,85,85,88,87	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Vital Signs	DBP >120 mmHg w/>20 mmHg ↑ BL; n=86,84,85,85,88,87	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Vital Signs	Pulse >120 bpm w/>20 bpm ↑ BL; n=86,84,85,85,88,87	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Vital Signs	Pulse <50 bpm w/>20 bpm ↓ BL; n=86,84,85,85,88,87	1 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Abnormalities in Vital Signs	Temperature >38C w/≥1C ↑ BL; n=86,84,85,84,88,87	0 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Vital Signs	DBP >120 mmHg w/>20 mmHg ↑ BL; n=86,84,85,85,88,87	0 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Vital Signs	SBP <90 mmHg w/>30 mmHg ↓ BL; n=86,84,85,85,88,87	1 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Vital Signs	Temperature >38C w/≥1C ↑ BL; n=86,84,85,84,88,87	0 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Vital Signs	SBP >180 mmHg w/>40 mmHg ↑ BL; n=86,84,85,85,88,87	0 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Vital Signs	Pulse <50 bpm w/>20 bpm ↓ BL; n=86,84,85,85,88,87	1 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Vital Signs	DBP <50 mmHg w/>20 mmHg ↓ BL; n=86,84,85,85,88,87	0 participants
DAC HYP 300 mg + Washout	Number of Participants With Abnormalities in Vital Signs	Pulse >120 bpm w/>20 bpm ↑ BL; n=86,84,85,85,88,87	0 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Vital Signs	Temperature >38C w/≥1C ↑ BL; n=86,84,85,84,88,87	0 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Vital Signs	Pulse >120 bpm w/>20 bpm ↑ BL; n=86,84,85,85,88,87	0 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Vital Signs	DBP >120 mmHg w/>20 mmHg ↑ BL; n=86,84,85,85,88,87	0 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Vital Signs	SBP <90 mmHg w/>30 mmHg ↓ BL; n=86,84,85,85,88,87	0 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Vital Signs	Pulse <50 bpm w/>20 bpm ↓ BL; n=86,84,85,85,88,87	0 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Vital Signs	SBP >180 mmHg w/>40 mmHg ↑ BL; n=86,84,85,85,88,87	0 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Abnormalities in Vital Signs	DBP <50 mmHg w/>20 mmHg ↓ BL; n=86,84,85,85,88,87	0 participants

Primary

Number of Participants With Development of Anti-DAC Antibodies (ADAb) and Neutralizing Antibodies (NAb) Post-baseline

Number of participants positive and negative for ADAb and NAb, based on all post-baseline immunogenicity assessments during treatment period and follow-up. Participants are stratified differently in this Outcome Measure as per the pre-specified statistical analysis plan.

Time frame: Up to 72 weeks

Population: All participants in the Safety Population (all randomized participants who received study treatment) with a post-baseline ADAb assessment.

Arm	Measure	Group	Value (NUMBER)
Placebo + DAC HYP 150 mg	Number of Participants With Development of Anti-DAC Antibodies (ADAb) and Neutralizing Antibodies (NAb) Post-baseline	ADAb Positive	7 participants
Placebo + DAC HYP 150 mg	Number of Participants With Development of Anti-DAC Antibodies (ADAb) and Neutralizing Antibodies (NAb) Post-baseline	ADAb Negative	162 participants
Placebo + DAC HYP 150 mg	Number of Participants With Development of Anti-DAC Antibodies (ADAb) and Neutralizing Antibodies (NAb) Post-baseline	NAb Positive	4 participants
Placebo + DAC HYP 150 mg	Number of Participants With Development of Anti-DAC Antibodies (ADAb) and Neutralizing Antibodies (NAb) Post-baseline	NAb Negative	165 participants
Placebo + DAC HYP 300 mg	Number of Participants With Development of Anti-DAC Antibodies (ADAb) and Neutralizing Antibodies (NAb) Post-baseline	NAb Negative	167 participants
Placebo + DAC HYP 300 mg	Number of Participants With Development of Anti-DAC Antibodies (ADAb) and Neutralizing Antibodies (NAb) Post-baseline	ADAb Positive	21 participants
Placebo + DAC HYP 300 mg	Number of Participants With Development of Anti-DAC Antibodies (ADAb) and Neutralizing Antibodies (NAb) Post-baseline	NAb Positive	4 participants
Placebo + DAC HYP 300 mg	Number of Participants With Development of Anti-DAC Antibodies (ADAb) and Neutralizing Antibodies (NAb) Post-baseline	ADAb Negative	150 participants
DAC HYP 150 mg + Washout	Number of Participants With Development of Anti-DAC Antibodies (ADAb) and Neutralizing Antibodies (NAb) Post-baseline	NAb Negative	169 participants
DAC HYP 150 mg + Washout	Number of Participants With Development of Anti-DAC Antibodies (ADAb) and Neutralizing Antibodies (NAb) Post-baseline	ADAb Negative	167 participants
DAC HYP 150 mg + Washout	Number of Participants With Development of Anti-DAC Antibodies (ADAb) and Neutralizing Antibodies (NAb) Post-baseline	NAb Positive	1 participants
DAC HYP 150 mg + Washout	Number of Participants With Development of Anti-DAC Antibodies (ADAb) and Neutralizing Antibodies (NAb) Post-baseline	ADAb Positive	3 participants

Primary

Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities

Hematology parameters evaluated include: white blood cells, lymphocytes, neutrophils, red blood cells (RBC), hemoglobin, and platelets.

Time frame: Up to 72 Weeks

Population: Number of participants in the safety population (all randomized participants who received study treatment) with at least one post-baseline value.

Arm	Measure	Group	Value (NUMBER)
Placebo + DAC HYP 150 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	White Blood Cell Count <3.0*10^9 cells/L	0 participants
Placebo + DAC HYP 150 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	White Blood Cell Count ≥16.0*10^9 cells/L	4 participants
Placebo + DAC HYP 150 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Lymphocytes <0.8*10^9 cells/L	5 participants
Placebo + DAC HYP 150 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Lymphocytes <0.5*10^9 cells/L	1 participants
Placebo + DAC HYP 150 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Lymphocytes >12*10^9 cells/L	0 participants
Placebo + DAC HYP 150 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Neutrophils ≤1.0*10^9 cells/L	0 participants
Placebo + DAC HYP 150 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Neutrophils <1.5*10^9 cells/L	0 participants
Placebo + DAC HYP 150 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Neutrophils ≥12*10^9 cells/L	4 participants
Placebo + DAC HYP 150 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	RBC Count ≤3.3*10^12 cells/L	0 participants
Placebo + DAC HYP 150 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	RBC Count ≥6.8*10^12 cells/L	0 participants
Placebo + DAC HYP 150 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Hemoglobin ≤100 g/L	1 participants
Placebo + DAC HYP 150 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Platelet Count ≤100*10^9 cells/L	0 participants
Placebo + DAC HYP 150 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Platelet Count ≥600*10^9 cells/L	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Lymphocytes <0.8*10^9 cells/L	4 participants
Placebo + DAC HYP 300 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Platelet Count ≥600*10^9 cells/L	2 participants
Placebo + DAC HYP 300 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	White Blood Cell Count <3.0*10^9 cells/L	3 participants
Placebo + DAC HYP 300 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Neutrophils ≥12*10^9 cells/L	3 participants
Placebo + DAC HYP 300 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Hemoglobin ≤100 g/L	5 participants
Placebo + DAC HYP 300 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Neutrophils ≤1.0*10^9 cells/L	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	White Blood Cell Count ≥16.0*10^9 cells/L	2 participants
Placebo + DAC HYP 300 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	RBC Count ≤3.3*10^12 cells/L	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Platelet Count ≤100*10^9 cells/L	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	RBC Count ≥6.8*10^12 cells/L	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Lymphocytes >12*10^9 cells/L	0 participants
Placebo + DAC HYP 300 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Neutrophils <1.5*10^9 cells/L	4 participants
Placebo + DAC HYP 300 mg	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Lymphocytes <0.5*10^9 cells/L	0 participants
DAC HYP 150 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Neutrophils <1.5*10^9 cells/L	2 participants
DAC HYP 150 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	RBC Count ≤3.3*10^12 cells/L	0 participants
DAC HYP 150 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Neutrophils ≥12*10^9 cells/L	2 participants
DAC HYP 150 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Lymphocytes <0.5*10^9 cells/L	1 participants
DAC HYP 150 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Lymphocytes <0.8*10^9 cells/L	6 participants
DAC HYP 150 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	White Blood Cell Count <3.0*10^9 cells/L	3 participants
DAC HYP 150 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Lymphocytes >12*10^9 cells/L	0 participants
DAC HYP 150 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	White Blood Cell Count ≥16.0*10^9 cells/L	1 participants
DAC HYP 150 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Hemoglobin ≤100 g/L	3 participants
DAC HYP 150 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Neutrophils ≤1.0*10^9 cells/L	1 participants
DAC HYP 150 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Platelet Count ≤100*10^9 cells/L	0 participants
DAC HYP 150 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	RBC Count ≥6.8*10^12 cells/L	0 participants
DAC HYP 150 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Platelet Count ≥600*10^9 cells/L	1 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Neutrophils ≥12*10^9 cells/L	1 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Lymphocytes <0.8*10^9 cells/L	3 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Lymphocytes <0.5*10^9 cells/L	1 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Platelet Count ≤100*10^9 cells/L	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Lymphocytes >12*10^9 cells/L	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Neutrophils ≤1.0*10^9 cells/L	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Neutrophils <1.5*10^9 cells/L	2 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	RBC Count ≤3.3*10^12 cells/L	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	RBC Count ≥6.8*10^12 cells/L	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Platelet Count ≥600*10^9 cells/L	0 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Hemoglobin ≤100 g/L	3 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	White Blood Cell Count <3.0*10^9 cells/L	4 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	White Blood Cell Count ≥16.0*10^9 cells/L	1 participants
DAC HYP 300 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	RBC Count ≤3.3*10^12 cells/L	0 participants
DAC HYP 300 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Neutrophils ≤1.0*10^9 cells/L	0 participants
DAC HYP 300 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	RBC Count ≥6.8*10^12 cells/L	0 participants
DAC HYP 300 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Lymphocytes <0.8*10^9 cells/L	2 participants
DAC HYP 300 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Platelet Count ≤100*10^9 cells/L	0 participants
DAC HYP 300 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	White Blood Cell Count ≥16.0*10^9 cells/L	3 participants
DAC HYP 300 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Hemoglobin ≤100 g/L	3 participants
DAC HYP 300 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Lymphocytes >12*10^9 cells/L	0 participants
DAC HYP 300 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	White Blood Cell Count <3.0*10^9 cells/L	3 participants
DAC HYP 300 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Platelet Count ≥600*10^9 cells/L	1 participants
DAC HYP 300 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Neutrophils ≥12*10^9 cells/L	4 participants
DAC HYP 300 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Neutrophils <1.5*10^9 cells/L	5 participants
DAC HYP 300 mg + Washout	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Lymphocytes <0.5*10^9 cells/L	1 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Hemoglobin ≤100 g/L	3 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	RBC Count ≤3.3*10^12 cells/L	0 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Platelet Count ≤100*10^9 cells/L	1 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Neutrophils ≤1.0*10^9 cells/L	1 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Neutrophils <1.5*10^9 cells/L	2 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Lymphocytes <0.8*10^9 cells/L	5 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Lymphocytes <0.5*10^9 cells/L	0 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	RBC Count ≥6.8*10^12 cells/L	0 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	White Blood Cell Count ≥16.0*10^9 cells/L	1 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Neutrophils ≥12*10^9 cells/L	2 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Lymphocytes >12*10^9 cells/L	0 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	White Blood Cell Count <3.0*10^9 cells/L	2 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities	Platelet Count ≥600*10^9 cells/L	0 participants

Primary

Number of Participants With Treatment-emergent Adverse Events (AEs)

Treatment-emergent AE: any untoward medical occurrence after the first dose of study treatment that did not necessarily have a causal relationship with this treatment. Serious AE (SAE): any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigator, placed the subject at immediate risk of death (a life-threatening event); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect. An SAE could also have been a medically significant event that, in the opinion of the Investigator, jeopardized the subject or required intervention to prevent one of the other outcomes listed in the definition above.

Time frame: Up to 72 weeks

Population: Safety population: all randomized participants who received study treatment. Participants who discontinued study treatment due to an AE and/or withdrew from the study due to an AE that started prior to 205MS202 (NCT00870740) and that was treatment-emergent under 205MS201 (NCT00390221) are included in this summary.

Arm	Measure	Group	Value (NUMBER)
Placebo + DAC HYP 150 mg	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with an SAE	15 participants
Placebo + DAC HYP 150 mg	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with an AE	61 participants
Placebo + DAC HYP 150 mg	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with a moderate or severe AE	37 participants
Placebo + DAC HYP 150 mg	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with a severe AE	1 participants
Placebo + DAC HYP 150 mg	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with a possibly/definitely related AE	18 participants
Placebo + DAC HYP 300 mg	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with an AE	57 participants
Placebo + DAC HYP 300 mg	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with an SAE	11 participants
Placebo + DAC HYP 300 mg	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with a possibly/definitely related AE	12 participants
Placebo + DAC HYP 300 mg	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with a severe AE	3 participants
Placebo + DAC HYP 300 mg	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with a moderate or severe AE	33 participants
DAC HYP 150 mg + Washout	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with a severe AE	3 participants
DAC HYP 150 mg + Washout	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with a moderate or severe AE	45 participants
DAC HYP 150 mg + Washout	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with an SAE	18 participants
DAC HYP 150 mg + Washout	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with a possibly/definitely related AE	24 participants
DAC HYP 150 mg + Washout	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with an AE	70 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with an AE	57 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with a possibly/definitely related AE	13 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with a moderate or severe AE	41 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with a severe AE	2 participants
DAC HYP 150 mg for 2 Years	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with an SAE	15 participants
DAC HYP 300 mg + Washout	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with a moderate or severe AE	35 participants
DAC HYP 300 mg + Washout	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with a possibly/definitely related AE	22 participants
DAC HYP 300 mg + Washout	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with an AE	61 participants
DAC HYP 300 mg + Washout	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with an SAE	15 participants
DAC HYP 300 mg + Washout	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with a severe AE	4 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with an SAE	11 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with an AE	62 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with a severe AE	4 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with a possibly/definitely related AE	22 participants
DAC HYP 300 mg for 2 Years	Number of Participants With Treatment-emergent Adverse Events (AEs)	Participants with a moderate or severe AE	35 participants

Secondary

Adjusted Annualized Relapse Rate

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 Independent Neurology Evaluation Committee (INEC). Relapse rate is calculated as: (Total number of relapses that occurred during the 205MS202 \[NCT00870740\] treatment phase divided by the total number of days followed in the treatment phase for 205MS202), multiplied by 365 days. Participants who received an alternative multiple sclerosis (MS) medication during 205MS201 (NCT00390221; Year 1) are not included in the summary of relapses and relapse rate for this study (Year 2). Participants are stratified differently in this Outcome Measure as per the pre-specified statistical analysis plan.

Time frame: Up to 72 weeks

Population: Per-protocol population: all randomized participants who received study treatment, excluding 18 participants from a single site (protocol violation) plus 75 participants for whom the time between the last dose of study treatment in 205MS201 (NCT00390221) and the first dose in 205MS202 (NCT00870740) was 56 days or longer.

Arm	Measure	Value (NUMBER)
Placebo + DAC HYP 150 mg	Adjusted Annualized Relapse Rate	0.179 relapses per person-years
Placebo + DAC HYP 300 mg	Adjusted Annualized Relapse Rate	0.302 relapses per person-years
DAC HYP 150 mg + Washout	Adjusted Annualized Relapse Rate	0.165 relapses per person-years

Secondary

Estimated Proportion of Participants With a Relapse

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 INEC. Estimated using Kaplan-Meier analysis where time to first relapse is calculated from date of first dose in the study to date of first confirmed relapse. Participants who received an alternative MS medication before the first relapse were censored at the time of taking the alternative MS medication.

Time frame: Up to 72 weeks

Arm	Measure	Value (NUMBER)
Placebo + DAC HYP 150 mg	Estimated Proportion of Participants With a Relapse	0.186 proportion of participants
Placebo + DAC HYP 300 mg	Estimated Proportion of Participants With a Relapse	0.166 proportion of participants
DAC HYP 150 mg + Washout	Estimated Proportion of Participants With a Relapse	0.249 proportion of participants
DAC HYP 150 mg for 2 Years	Estimated Proportion of Participants With a Relapse	0.160 proportion of participants
DAC HYP 300 mg + Washout	Estimated Proportion of Participants With a Relapse	0.235 proportion of participants
DAC HYP 300 mg for 2 Years	Estimated Proportion of Participants With a Relapse	0.111 proportion of participants

Secondary

Mean Number of New Gadolinium-enhancing Lesions

Evaluated by magnetic resonance imaging (MRI) by a central reader. Number of new Gd lesions since the previous scan (the previous scan for Week 20 was Week 52 of study 205MS201 \[NCT00390221\]). The number of Gd lesions may be imputed using last observation carried forward or using the mean value across all subjects within the treatment group. Baseline visits are not imputed. Participants are stratified differently in this Outcome Measure as per the pre-specified statistical analysis plan.

Time frame: Week 20, Week 52

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo + DAC HYP 150 mg	Mean Number of New Gadolinium-enhancing Lesions	Week 20	0.3 lesions	Standard Deviation 1.01
Placebo + DAC HYP 150 mg	Mean Number of New Gadolinium-enhancing Lesions	Week 52	0.2 lesions	Standard Deviation 0.8
Placebo + DAC HYP 300 mg	Mean Number of New Gadolinium-enhancing Lesions	Week 20	1.1 lesions	Standard Deviation 2.34
Placebo + DAC HYP 300 mg	Mean Number of New Gadolinium-enhancing Lesions	Week 52	0.2 lesions	Standard Deviation 0.64
DAC HYP 150 mg + Washout	Mean Number of New Gadolinium-enhancing Lesions	Week 20	0.2 lesions	Standard Deviation 0.51
DAC HYP 150 mg + Washout	Mean Number of New Gadolinium-enhancing Lesions	Week 52	0.2 lesions	Standard Deviation 1.21

Secondary

Mean Number of New or Newly-enlarging T2 Hyperintense Lesions

Lesions detected on T2-weighted sequences represent a range of histopathology related to MS, including edema, inflammation, demyelination, gliosis, and axon loss. Evaluated by MRI by a central reader. New or newly enlarging T2 lesions since baseline of study 205MS202 (NCT00870740). For post-baseline visits, the number of T2 lesions may be imputed using the mean value across all participants within the treatment group, if the participant has non-missing baseline data. Baseline visits are not imputed. Participants are stratified differently in this Outcome Measure as per the pre-specified statistical analysis plan.

Time frame: Baseline, Week 20, Week 52

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo + DAC HYP 150 mg	Mean Number of New or Newly-enlarging T2 Hyperintense Lesions	Week 20	1.1 lesions	Standard Deviation 2.26
Placebo + DAC HYP 150 mg	Mean Number of New or Newly-enlarging T2 Hyperintense Lesions	Baseline	46.0 lesions	Standard Deviation 36.48
Placebo + DAC HYP 150 mg	Mean Number of New or Newly-enlarging T2 Hyperintense Lesions	Week 52	2.1 lesions	Standard Deviation 3.68
Placebo + DAC HYP 300 mg	Mean Number of New or Newly-enlarging T2 Hyperintense Lesions	Week 20	2.6 lesions	Standard Deviation 6.33
Placebo + DAC HYP 300 mg	Mean Number of New or Newly-enlarging T2 Hyperintense Lesions	Baseline	41.1 lesions	Standard Deviation 36.36
Placebo + DAC HYP 300 mg	Mean Number of New or Newly-enlarging T2 Hyperintense Lesions	Week 52	3.3 lesions	Standard Deviation 6.95
DAC HYP 150 mg + Washout	Mean Number of New or Newly-enlarging T2 Hyperintense Lesions	Baseline	39.8 lesions	Standard Deviation 32.63
DAC HYP 150 mg + Washout	Mean Number of New or Newly-enlarging T2 Hyperintense Lesions	Week 52	1.2 lesions	Standard Deviation 4.33
DAC HYP 150 mg + Washout	Mean Number of New or Newly-enlarging T2 Hyperintense Lesions	Week 20	0.5 lesions	Standard Deviation 1.28

Secondary

Mean Percentage Change From Baseline in Total Lesion Volume of T2 Hyperintense Lesions

Lesions detected on T2-weighted sequences represent a range of histopathology related to MS, including edema, inflammation, demyelination, gliosis, and axon loss. Evaluated by MRI by a central reader. Baseline values = baseline for study 205MS202 (NCT00870740). For post-baseline visits, the total volume of T2 lesions may be imputed using the mean value across all subjects within the treatment group. Baseline visits are not imputed.

Time frame: Baseline, Week 52

Population: Per-protocol population (with a baseline and post-baseline assessment): randomized participants who received study treatment, excluding 18 participants from a single site (protocol violation) plus 75 for whom the time between the last dose of study treatment in 205MS201 (NCT00390221) and the first dose in 205MS202 (NCT00870740) was ≥ 56 days.

Arm	Measure	Value (MEAN)	Dispersion
Placebo + DAC HYP 150 mg	Mean Percentage Change From Baseline in Total Lesion Volume of T2 Hyperintense Lesions	-7.75 percentage change in volume	Standard Deviation 21.952
Placebo + DAC HYP 300 mg	Mean Percentage Change From Baseline in Total Lesion Volume of T2 Hyperintense Lesions	-8.44 percentage change in volume	Standard Deviation 13.942
DAC HYP 150 mg + Washout	Mean Percentage Change From Baseline in Total Lesion Volume of T2 Hyperintense Lesions	-0.78 percentage change in volume	Standard Deviation 22.243
DAC HYP 150 mg for 2 Years	Mean Percentage Change From Baseline in Total Lesion Volume of T2 Hyperintense Lesions	-4.90 percentage change in volume	Standard Deviation 25.935
DAC HYP 300 mg + Washout	Mean Percentage Change From Baseline in Total Lesion Volume of T2 Hyperintense Lesions	-5.40 percentage change in volume	Standard Deviation 16.672
DAC HYP 300 mg for 2 Years	Mean Percentage Change From Baseline in Total Lesion Volume of T2 Hyperintense Lesions	-8.98 percentage change in volume	Standard Deviation 11.673

Secondary

Mean Percentage Change From Baseline in Total Volume of Non-gadolinium (Gd)-Enhancing T1 Hypointense Lesions

T1-weighted scans detect areas of hypointensity that represent a greater degree of tissue destruction and axon loss than T2 hyperintense lesions and are more highly correlated with clinical disability measures and neurological deficit. Evaluated by MRI by a central reader. Baseline values = baseline for study 205MS202 (NCT00870740). For post-baseline visits, the total volume of T1 lesions may be imputed using the mean value across all participants within the treatment group. Baseline visits are not imputed.

Time frame: Baseline, Week 52

Arm	Measure	Value (MEAN)	Dispersion
Placebo + DAC HYP 150 mg	Mean Percentage Change From Baseline in Total Volume of Non-gadolinium (Gd)-Enhancing T1 Hypointense Lesions	-3.99 percentage change in volume	Standard Deviation 35.543
Placebo + DAC HYP 300 mg	Mean Percentage Change From Baseline in Total Volume of Non-gadolinium (Gd)-Enhancing T1 Hypointense Lesions	-7.15 percentage change in volume	Standard Deviation 39.932
DAC HYP 150 mg + Washout	Mean Percentage Change From Baseline in Total Volume of Non-gadolinium (Gd)-Enhancing T1 Hypointense Lesions	-5.51 percentage change in volume	Standard Deviation 49.97
DAC HYP 150 mg for 2 Years	Mean Percentage Change From Baseline in Total Volume of Non-gadolinium (Gd)-Enhancing T1 Hypointense Lesions	-13.89 percentage change in volume	Standard Deviation 18.089
DAC HYP 300 mg + Washout	Mean Percentage Change From Baseline in Total Volume of Non-gadolinium (Gd)-Enhancing T1 Hypointense Lesions	-6.72 percentage change in volume	Standard Deviation 22.721
DAC HYP 300 mg for 2 Years	Mean Percentage Change From Baseline in Total Volume of Non-gadolinium (Gd)-Enhancing T1 Hypointense Lesions	-16.59 percentage change in volume	Standard Deviation 17.436

Secondary

Mean Volume of New T1 Hypointense Lesions

T1-weighted scans detect areas of hypointensity that represent a greater degree of tissue destruction and axon loss than T2 hyperintense lesions and are more highly correlated with clinical disability measures and neurological deficit. Evaluated by MRI by a central reader. Baseline is volume of new T1 hypointense lesions since baseline in study 205MS201 (NCT00390221). Scans at Week 20 and Week 52 in 205MS202 are relative to baseline in 205MS202 (NCT00870740). For post-baseline visits, the total volume of T1 lesions may be imputed using the mean value across all subjects within the treatment group. Baseline visits are not imputed.

Time frame: Baseline, Week 20, Week 52

Population: Per-protocol population: randomized participants who received study treatment, excluding 18 participants from a single site (protocol violation) plus 75 for whom the time between the last dose of study treatment in 205MS201 (NCT00390221) and the first dose in 205MS202 (NCT00870740) was ≥ 56 days; n=participants with measurement at given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo + DAC HYP 150 mg	Mean Volume of New T1 Hypointense Lesions	Week 20; n=81, 74, 62, 65, 63, 63	36.17 mm^3	Standard Deviation 114.019
Placebo + DAC HYP 150 mg	Mean Volume of New T1 Hypointense Lesions	Baseline; n=83, 79, 63, 64, 66, 64	232.13 mm^3	Standard Deviation 467.811
Placebo + DAC HYP 150 mg	Mean Volume of New T1 Hypointense Lesions	Week 52; n=81, 74, 62, 65, 63, 63	88.46 mm^3	Standard Deviation 239.741
Placebo + DAC HYP 300 mg	Mean Volume of New T1 Hypointense Lesions	Week 20; n=81, 74, 62, 65, 63, 63	62.76 mm^3	Standard Deviation 143.28
Placebo + DAC HYP 300 mg	Mean Volume of New T1 Hypointense Lesions	Baseline; n=83, 79, 63, 64, 66, 64	228.90 mm^3	Standard Deviation 390.587
Placebo + DAC HYP 300 mg	Mean Volume of New T1 Hypointense Lesions	Week 52; n=81, 74, 62, 65, 63, 63	109.42 mm^3	Standard Deviation 231.734
DAC HYP 150 mg + Washout	Mean Volume of New T1 Hypointense Lesions	Week 20; n=81, 74, 62, 65, 63, 63	161.98 mm^3	Standard Deviation 829.086
DAC HYP 150 mg + Washout	Mean Volume of New T1 Hypointense Lesions	Baseline; n=83, 79, 63, 64, 66, 64	126.50 mm^3	Standard Deviation 288.58
DAC HYP 150 mg + Washout	Mean Volume of New T1 Hypointense Lesions	Week 52; n=81, 74, 62, 65, 63, 63	142.31 mm^3	Standard Deviation 628.5
DAC HYP 150 mg for 2 Years	Mean Volume of New T1 Hypointense Lesions	Week 20; n=81, 74, 62, 65, 63, 63	6.29 mm^3	Standard Deviation 24.095
DAC HYP 150 mg for 2 Years	Mean Volume of New T1 Hypointense Lesions	Baseline; n=83, 79, 63, 64, 66, 64	94.20 mm^3	Standard Deviation 281.45
DAC HYP 150 mg for 2 Years	Mean Volume of New T1 Hypointense Lesions	Week 52; n=81, 74, 62, 65, 63, 63	17.18 mm^3	Standard Deviation 39.881
DAC HYP 300 mg + Washout	Mean Volume of New T1 Hypointense Lesions	Week 20; n=81, 74, 62, 65, 63, 63	12.37 mm^3	Standard Deviation 32.361
DAC HYP 300 mg + Washout	Mean Volume of New T1 Hypointense Lesions	Baseline; n=83, 79, 63, 64, 66, 64	52.26 mm^3	Standard Deviation 184.17
DAC HYP 300 mg + Washout	Mean Volume of New T1 Hypointense Lesions	Week 52; n=81, 74, 62, 65, 63, 63	43.60 mm^3	Standard Deviation 88.084
DAC HYP 300 mg for 2 Years	Mean Volume of New T1 Hypointense Lesions	Baseline; n=83, 79, 63, 64, 66, 64	44.92 mm^3	Standard Deviation 150.363
DAC HYP 300 mg for 2 Years	Mean Volume of New T1 Hypointense Lesions	Week 52; n=81, 74, 62, 65, 63, 63	21.42 mm^3	Standard Deviation 82.566
DAC HYP 300 mg for 2 Years	Mean Volume of New T1 Hypointense Lesions	Week 20; n=81, 74, 62, 65, 63, 63	4.66 mm^3	Standard Deviation 19.386

Secondary

Rate of Percentage Change From Baseline in Mean Total Brain Volume

Total brain volume was measured by MRI and analyzed by a central reader. Rate of percentage change from baseline calculated using an analysis of covariance adjusting for baseline normalized brain volume. Baseline values = baseline for study 205MS202 (NCT00870740). Missing values post-baseline were imputed using the average value across subjects in the treatment group.

Time frame: Baseline, Week 52

Arm	Measure	Value (NUMBER)
Placebo + DAC HYP 150 mg	Rate of Percentage Change From Baseline in Mean Total Brain Volume	-0.772 rate of percentage change
Placebo + DAC HYP 300 mg	Rate of Percentage Change From Baseline in Mean Total Brain Volume	-0.930 rate of percentage change
DAC HYP 150 mg + Washout	Rate of Percentage Change From Baseline in Mean Total Brain Volume	-0.622 rate of percentage change
DAC HYP 150 mg for 2 Years	Rate of Percentage Change From Baseline in Mean Total Brain Volume	-0.528 rate of percentage change
DAC HYP 300 mg + Washout	Rate of Percentage Change From Baseline in Mean Total Brain Volume	-0.505 rate of percentage change
DAC HYP 300 mg for 2 Years	Rate of Percentage Change From Baseline in Mean Total Brain Volume	-0.452 rate of percentage change

Source: ClinicalTrials.gov · Data processed: Mar 21, 2026

Safety and Efficacy Extension Study of Daclizumab High Yield Process (DAC HYP) in Participants With Multiple Sclerosis Who Have Completed Study 205MS201 (NCT00390221) to Treat Relapsing-Remitting Multiple Sclerosis

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Number of Participants With Abnormalities in Blood Chemistry Laboratory Data

Number of Participants With Abnormalities in Vital Signs

Number of Participants With Development of Anti-DAC Antibodies (ADAb) and Neutralizing Antibodies (NAb) Post-baseline

Number of Participants With Potentially Clinically Significant Hematology Laboratory Abnormalities

Number of Participants With Treatment-emergent Adverse Events (AEs)

Adjusted Annualized Relapse Rate

Estimated Proportion of Participants With a Relapse

Mean Number of New Gadolinium-enhancing Lesions

Mean Number of New or Newly-enlarging T2 Hyperintense Lesions

Mean Percentage Change From Baseline in Total Lesion Volume of T2 Hyperintense Lesions

Mean Percentage Change From Baseline in Total Volume of Non-gadolinium (Gd)-Enhancing T1 Hypointense Lesions

Mean Volume of New T1 Hypointense Lesions

Rate of Percentage Change From Baseline in Mean Total Brain Volume