Study to Assess the Efficacy, Safety, Tolerability, and P... | NCT01864148

ID	Type	Description	Link
2011-006262-40	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
BIIB033, 3 mg/kg	Experimental	BIIB033 3 mg/kg once every 4 weeks intravenous (IV) infusion up to Week 72. Avonex once-weekly intramuscular (IM) injection up to Week 84.	Drug: BIIB033 Drug: Avonex
BIIB033, 10 mg/kg	Experimental	BIIB033 10 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	Drug: BIIB033 Drug: Avonex
BIIB033, 30 mg/kg	Experimental	BIIB033 30 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	Drug: BIIB033 Drug: Avonex
BIIB033, 100 mg/kg	Experimental	BIIB033 100 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	Drug: BIIB033 Drug: Avonex
Placebo	Placebo Comparator	Placebo once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	Other: Placebo

Name	Type	Description	Arm Group Labels	Other Names
BIIB033	Drug		BIIB033, 10 mg/kg BIIB033, 100 mg/kg BIIB033, 3 mg/kg BIIB033, 30 mg/kg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Proportion of Participants Confirmed as Improvement Responders for Primary Multicomponent Endpoint	Estimated proportion of participants experiencing confirmed improvement in any 1 or more of the following components: a ≥1 point decrease in the Expanded Disability Status Scale (EDSS) score from a baseline score of <=6.0 (decrease sustained for ≥3 months); a ≥15% improvement from baseline in time to complete 9-Hole Peg Test (9HPT) by either hand (improvement sustained for ≥3 months for the same hand), where the time is the average time of 2 trials per hand at the same visit; a ≥15% improvement from baseline in time to complete Timed 25-Foot Walk (T25FW) test (improvement sustained for ≥3 months), where the time is the average time of 2 trials at the same visit; or a ≥15% improvement from baseline 3-Second Paced Auditory Serial Addition Test (PASAT-3) score (improvement sustained for 3 months or greater). Estimated proportion of responders is based on logistic regression adjusted for multiple sclerosis (MS) type, region and baseline component assessments.	72 weeks

Secondary Outcomes

Measure	Description	Time Frame
Proportion of Participants Confirmed as Worsening Responders for Primary Multicomponent Endpoint	Estimated proportion of participants experiencing confirmed clinical worsening in 1 or more components of the multicomponent endpoint (EDSS, T25FW, 9HPT, or PASAT-3) over 72 weeks, defined as: a ≥1.0 point increase in EDSS from a baseline score of ≤5.5 or a ≥0.5 point increase from a baseline score equal to 6.0 (increase sustained for 3 months or greater); a ≥15%worsening from baseline in time to complete T25FW test (worsening sustained for 3 months or greater), where the time is the average of 2 trials at the same visit; a ≥15% worsening from baseline in time to complete 9HPT by either hand (worsening sustained for 3 months or greater for the same hand), where the time is the average of 2 trials for each hand at the same visit; a ≥15% worsening from baseline in PASAT-3 score (worsening sustained for 3 months or greater). Estimated proportion of responders is based on logistic regression adjusted for MS type, region and baseline component assessments.

Eligibility Module

Name	Affiliation	Role
Medical Director	Biogen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
North Central Neurology Assoc PC		Cullman	Alabama	35058	United States
Phoenix Neurological Associates

PubMed Identifier	Type	Citation	Retractions
31285147	Derived	Cadavid D, Mellion M, Hupperts R, Edwards KR, Calabresi PA, Drulovic J, Giovannoni G, Hartung HP, Arnold DL, Fisher E, Rudick R, Mi S, Chai Y, Li J, Zhang Y, Cheng W, Xu L, Zhu B, Green SM, Chang I, Deykin A, Sheikh SI; SYNERGY study investigators. Safety and efficacy of opicinumab in patients with relapsing multiple sclerosis (SYNERGY): a randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2019 Sep;18(9):845-856. doi: 10.1016/S1474-4422(19)30137-1. Epub 2019 Jul 5.
26396053

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Placebo once every 4 weeks intravenous (IV) infusion up to Week 72. Avonex once-weekly intramuscular (IM) injection up to Week 84.
FG001	BIIB033, 3 mg/kg	BIIB033 3 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Placebo	Placebo once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.
BG001	BIIB033, 3 mg/kg	BIIB033 3 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.
BG002	BIIB033, 10 mg/kg	BIIB033 10 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.
BG003	BIIB033, 30 mg/kg	BIIB033 30 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.
BG004	BIIB033, 100 mg/kg	BIIB033 100 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.
BG005	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Proportion of Participants Confirmed as Improvement Responders for Primary Multicomponent Endpoint

Estimated proportion of participants experiencing confirmed improvement in any 1 or more of the following components: a ≥1 point decrease in the Expanded Disability Status Scale (EDSS) score from a baseline score of <=6.0 (decrease sustained for ≥3 months); a ≥15% improvement from baseline in time to complete 9-Hole Peg Test (9HPT) by either hand (improvement sustained for ≥3 months for the same hand), where the time is the average time of 2 trials per hand at the same visit; a ≥15% improvement from baseline in time to complete Timed 25-Foot Walk (T25FW) test (improvement sustained for ≥3 months), where the time is the average time of 2 trials at the same visit; or a ≥15% improvement from baseline 3-Second Paced Auditory Serial Addition Test (PASAT-3) score (improvement sustained for 3 months or greater). Estimated proportion of responders is based on logistic regression adjusted for multiple sclerosis (MS) type, region and baseline component assessments.

Intent-to-treat population: all randomized participants who received at least 1 dose of study treatment and included in the efficacy analysis (6 participants were excluded due to study site Good Clinical Practice deviation).

Posted

Number

proportion of participants

72 weeks

ID	Title	Description
OG000	Placebo	Placebo once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.
OG001	BIIB033, 3 mg/kg	BIIB033 3 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.
OG002	BIIB033, 10 mg/kg	BIIB033 10 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.
OG003	BIIB033, 30 mg/kg	BIIB033 30 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.
OG004	BIIB033, 100 mg/kg	BIIB033 100 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.

Units	Counts
Participants	OG00091 OG00145 OG00294 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000.516 OG0010.511 OG0020.656 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Regression, Logistic	Odds ratios, 95% CI and p-values are based on logistic regression adjusted for MS type, region and baseline component assessments.	0.9584		Odds Ratio (OR)	0.98			2-Sided	95	0.46	2.07					Superiority or Other
OG000 OG002		Regression, Logistic

Secondary

Proportion of Participants Confirmed as Worsening Responders for Primary Multicomponent Endpoint

Estimated proportion of participants experiencing confirmed clinical worsening in 1 or more components of the multicomponent endpoint (EDSS, T25FW, 9HPT, or PASAT-3) over 72 weeks, defined as: a ≥1.0 point increase in EDSS from a baseline score of ≤5.5 or a ≥0.5 point increase from a baseline score equal to 6.0 (increase sustained for 3 months or greater); a ≥15%worsening from baseline in time to complete T25FW test (worsening sustained for 3 months or greater), where the time is the average of 2 trials at the same visit; a ≥15% worsening from baseline in time to complete 9HPT by either hand (worsening sustained for 3 months or greater for the same hand), where the time is the average of 2 trials for each hand at the same visit; a ≥15% worsening from baseline in PASAT-3 score (worsening sustained for 3 months or greater). Estimated proportion of responders is based on logistic regression adjusted for MS type, region and baseline component assessments.

Posted

Number

proportion of participants

72 weeks

ID	Title	Description
OG000	Placebo	Placebo once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.
OG001	BIIB033, 3 mg/kg

Secondary

Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) and Discontinuations Due to AEs

An AE was any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. An SAE was any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigators, placed the participant at immediate risk of death (a life-threatening event); however, this did not include an event that, had it occurred in a more severe form, might have caused death; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigators, could have jeopardized the participant or may have required intervention to prevent one of the other outcomes listed in the definition above.

Safety Population: all participants who received at least 1 dose of study treatment.

Posted

Number

participants

Up to 84 weeks

ID	Title	Description
OG000	Placebo	Placebo once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.
OG001	BIIB033, 3 mg/kg	BIIB033 3 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.
OG002

Secondary

Pharmacokinetics: BIIB033 Plasma Concentrations up to Week 84

PK Population: participants who received at least 1 dose of BIIB033 and had at least 1 serum concentration data point on record.

Posted

Mean

Standard Deviation

µg/mL

Up to 84 weeks

ID	Title	Description
OG000	BIIB033, 3 mg/kg	BIIB033 3 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.
OG001	BIIB033, 10 mg/kg	BIIB033 10 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.
OG002	BIIB033, 30 mg/kg	BIIB033 30 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.
OG003	BIIB033, 100 mg/kg	BIIB033 100 mg/kg once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Placebo once every 4 weeks IV infusion up to Week 72. Avonex once-weekly IM injection up to Week 84.	13	93	74	93
EG001	BIIB033 3 mg/kg	BIIB033 3 mg/kg once every 4 weeks IV infusion	4	45	38	45
EG002	BIIB033 10 mg/kg	BIIB033 10 mg/kg once every 4 weeks IV infusion	11	95	79	95
EG003	BIIB033 30 mg/kg	BIIB033 30 mg/kg once every 4 weeks IV infusion	20	93	70	93
EG004	BIIB033 100 mg/kg	BIIB033 100 mg/kg once every 4 weeks IV infusion	16	92	67	92

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hypochromic anaemia	Blood and lymphatic system disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG0030 affected93 at risk EG0040 affected92 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0021 affected95 at risk EG003
Myocardial ischaemia	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0011 affected45 at risk EG0020 affected95 at risk EG003
Ileus	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0021 affected95 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Bile duct stone	Hepatobiliary disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Cholecystitis acute	Hepatobiliary disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Drug-induced liver injury	Hepatobiliary disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Cystitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0002 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0011 affected45 at risk EG0020 affected95 at risk EG003
Femur fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0011 affected45 at risk EG0020 affected95 at risk EG003
Intentional overdose	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Hepatic enzyme increased	Investigations	MedDRA 18.1	Systematic Assessment	EG0001 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0021 affected95 at risk EG003
Thyroid adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Multiple sclerosis	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0021 affected95 at risk EG003
Multiple sclerosis relapse	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0007 affected93 at risk EG0012 affected45 at risk EG0026 affected95 at risk EG003
Radicular syndrome	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Secondary progressive multiple sclerosis	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Seizure	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Trigeminal neuralgia	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0011 affected45 at risk EG0020 affected95 at risk EG003
Acute psychosis	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Bipolar disorder	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Bipolar I disorder	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Suicidal ideation	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0021 affected95 at risk EG003
Menorrhagia	Reproductive system and breast disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003
Metrorrhagia	Reproductive system and breast disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0021 affected95 at risk EG003
Uterine polyp	Reproductive system and breast disorders	MedDRA 18.1	Systematic Assessment	EG0000 affected93 at risk EG0010 affected45 at risk EG0020 affected95 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0003 affected93 at risk EG0015 affected45 at risk EG0023 affected95 at risk EG0033 affected93 at risk EG0043 affected92 at risk
Asthenia	General disorders	MedDRA 18.1	Systematic Assessment	EG0008 affected93 at risk EG0011 affected45 at risk EG0025 affected95 at risk EG003
Chills	General disorders	MedDRA 18.1	Systematic Assessment	EG0005 affected93 at risk EG0014 affected45 at risk EG0024 affected95 at risk EG003
Fatigue	General disorders	MedDRA 18.1	Systematic Assessment	EG0008 affected93 at risk EG0016 affected45 at risk EG0025 affected95 at risk EG003
Influenza like illness	General disorders	MedDRA 18.1	Systematic Assessment	EG00037 affected93 at risk EG00117 affected45 at risk EG00251 affected95 at risk EG003
Pyrexia	General disorders	MedDRA 18.1	Systematic Assessment	EG0007 affected93 at risk EG0019 affected45 at risk EG0028 affected95 at risk EG003
Influenza	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0004 affected93 at risk EG0013 affected45 at risk EG0026 affected95 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG00016 affected93 at risk EG0013 affected45 at risk EG00212 affected95 at risk EG003
Pharyngitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0002 affected93 at risk EG0015 affected45 at risk EG0024 affected95 at risk EG003
Sinusitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0005 affected93 at risk EG0012 affected45 at risk EG0022 affected95 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG00013 affected93 at risk EG0014 affected45 at risk EG00221 affected95 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG00012 affected93 at risk EG0017 affected45 at risk EG00214 affected95 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG00010 affected93 at risk EG0010 affected45 at risk EG0024 affected95 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 18.1	Systematic Assessment	EG0003 affected93 at risk EG0012 affected45 at risk EG0025 affected95 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0003 affected93 at risk EG0012 affected45 at risk EG0024 affected95 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0009 affected93 at risk EG0013 affected45 at risk EG0029 affected95 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0003 affected93 at risk EG0013 affected45 at risk EG0022 affected95 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected93 at risk EG0013 affected45 at risk EG0021 affected95 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0005 affected93 at risk EG0011 affected45 at risk EG0025 affected95 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0004 affected93 at risk EG0015 affected45 at risk EG0025 affected95 at risk EG003
Headache	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG00023 affected93 at risk EG0018 affected45 at risk EG00219 affected95 at risk EG003
Multiple sclerosis relapse	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG00030 affected93 at risk EG00117 affected45 at risk EG00235 affected95 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0004 affected93 at risk EG0010 affected45 at risk EG0025 affected95 at risk EG003
Depressed mood	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0002 affected93 at risk EG0013 affected45 at risk EG0021 affected95 at risk EG003
Depression	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0006 affected93 at risk EG0012 affected45 at risk EG0026 affected95 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0001 affected93 at risk EG0012 affected45 at risk EG0024 affected95 at risk EG003

ID	Term
D020278	Demyelinating Autoimmune Diseases, CNS
D020274	Autoimmune Diseases of the Nervous System
D009422	Nervous System Diseases
D003711	Demyelinating Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Term
D016899	Interferon-beta
D007370	Interferon Type I
D007372	Interferons
D016207	Cytokines
D036341	Intercellular Signaling Peptides and Proteins
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D011506	Proteins
D001685	Biological Factors