Safety and Tolerability Study of MEDI-551, a B-cell Deple... | NCT01585766

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
MEDI-551 30 MG-IV	Experimental	Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.	Drug: MEDI-551 30 MG-IV
MEDI-551 60 MG-SC	Experimental	Participants received SC injection of 60 mg MEDI-551 on Day 1.	Drug: MEDI-551 60 MG-SC
MEDI-551 100 MG-IV	Experimental	Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15.	Drug: MEDI-551 100 MG-IV
MEDI-551 300 MG-SC	Experimental	Participants received SC injection of 300 mg MEDI-551 on Day 1.	Drug: MEDI-551 300 MG-SC
MEDI-551 600 MG-IV	Experimental	Participants received a fixed IV dose of 600 mg MEDI-551 infused on Days 1 and 15.	Drug: MEDI-551 600 MG-IV
PLACEBO-IV-SC	Placebo Comparator

Name	Type	Description	Arm Group Labels	Other Names
MEDI-551 30 MG-IV	Drug	Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.	MEDI-551 30 MG-IV

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A TEAE were the events between administration of study drug (Day 1) and Day 169 that were absent before treatment or that worsened relative to pre-treatment state. The AEs were summarized using Medical Dictionary for Regulatory Activities version 19.0	From study drug administration (Day 1) through the end of treatment period (Day 169)
Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)	A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death, life-threatening, initial or prolonged inpatient hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect in the offspring of a participant who received the study drug. The TESAEs were the events between administration of study drug (Day 1) and long term follow up period (up to 18 months after early discontinuation visit or 24-week treatment period) that were absent before treatment or that worsened relative to pre-treatment state. The AEs were summarized using Medical Dictionary for Regulatory Activities version 19.0	From study drug administration (Day 1) through the long term follow up period (up to 18 months after early discontinuation visit or 24 week treatment period).
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs	Any clinically significant change in laboratory evaluations were recorded as AEs. The following parameters were analyzed for laboratory evaluations: haematology, serum chemistry, and urinalysis. Number of participants with TEAEs related to laboratory evaluations were reported.	From study drug administration (Day 1) through the end of treatment period (Day 169)
Number of Participants With Vital Sign Abnormalities Reported as TEAEs

Secondary Outcomes

Measure	Description	Time Frame
Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-551	The time to reach the maximum observed serum concentration of MEDI-551.	Predose (Day 1) and Postdose (IV Cohorts only), Days 4 (SC Cohorts only), 8, 15 Predose and Postdose (IV Cohorts only), 29, 57, 85, 113, 141, and 169
Maximum Observed Serum Concentration (Cmax) of MEDI-551

Eligibility Module

Name	Affiliation	Role
Armando Flor	MedImmune LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Scottsdale	Arizona		United States
Research Site

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	PLACEBO-IV-SC	Participants received either a fixed IV dose of placebo matching MEDI-551 on Days 1 and 15 or SC injection on Day 1.
FG001	MEDI-551 30 Mg-IV	Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	PLACEBO-IV-SC	Participants received either a fixed IV dose of placebo matching MEDI-551 on Days 1 and 15 or SC injection on Day 1.
BG001	MEDI-551 30 Mg-IV	Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.
BG002	MEDI-551 60 Mg-SC	Participants received SC injection of 60 mg MEDI-551 on Day 1.
BG003	MEDI-551 100 Mg-IV	Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15.
BG004	MEDI-551 300 Mg-SC	Participants received SC injection of 300 mg MEDI-551 on Day 1.
BG005	MEDI-551 600 Mg-IV	Participants received a fixed IV dose of 600 mg MEDI-551 infused on Days 1 and 15.
BG006	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

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A TEAE were the events between administration of study drug (Day 1) and Day 169 that were absent before treatment or that worsened relative to pre-treatment state. The AEs were summarized using Medical Dictionary for Regulatory Activities version 19.0

Safety Population is defined as all participants who received any amount of study drug.

Posted

Count of Participants

Participants

From study drug administration (Day 1) through the end of treatment period (Day 169)

ID	Title	Description
OG000	PLACEBO-IV-SC	Participants received either a fixed IV dose of placebo matching MEDI-551 on Days 1 and 15 or SC injection on Day 1.
OG001	MEDI-551 30 Mg-IV	Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.
OG002	MEDI-551 60 Mg-SC	Participants received SC injection of 60 mg MEDI-551 on Day 1.
OG003	MEDI-551 100 Mg-IV	Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15.
OG004	MEDI-551 300 Mg-SC	Participants received SC injection of 300 mg MEDI-551 on Day 1.
OG005	MEDI-551 600 Mg-IV	Participants received a fixed IV dose of 600 mg MEDI-551 infused on Days 1 and 15.

Units	Counts
Participants	OG0007 OG0015 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0006 OG0015 OG0023 OG003

Primary

Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)

A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death, life-threatening, initial or prolonged inpatient hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect in the offspring of a participant who received the study drug. The TESAEs were the events between administration of study drug (Day 1) and long term follow up period (up to 18 months after early discontinuation visit or 24-week treatment period) that were absent before treatment or that worsened relative to pre-treatment state. The AEs were summarized using Medical Dictionary for Regulatory Activities version 19.0

Safety Population

Posted

Count of Participants

Participants

From study drug administration (Day 1) through the long term follow up period (up to 18 months after early discontinuation visit or 24 week treatment period).

ID	Title	Description
OG000	PLACEBO-IV-SC	Participants received either a fixed IV dose of placebo matching MEDI-551 on Days 1 and 15 or SC injection on Day 1.
OG001	MEDI-551 30 Mg-IV	Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.
OG002	MEDI-551 60 Mg-SC

Primary

Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs

Any clinically significant change in laboratory evaluations were recorded as AEs. The following parameters were analyzed for laboratory evaluations: haematology, serum chemistry, and urinalysis. Number of participants with TEAEs related to laboratory evaluations were reported.

Safety Population

Posted

Count of Participants

Participants

From study drug administration (Day 1) through the end of treatment period (Day 169)

ID	Title	Description
OG000	PLACEBO-IV-SC	Participants received either a fixed IV dose of placebo matching MEDI-551 on Days 1 and 15 or SC injection on Day 1.
OG001	MEDI-551 30 Mg-IV	Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.
OG002	MEDI-551 60 Mg-SC	Participants received SC injection of 60 mg MEDI-551 on Day 1.
OG003	MEDI-551 100 Mg-IV	Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15.

Primary

Number of Participants With Vital Sign Abnormalities Reported as TEAEs

Vital sign parameters included blood pressure, temperature, pulse rate, and respiratory rate. The number of participants with TEAEs related to vital signs in participants were reported.

Safety Population

Posted

Count of Participants

Participants

From study drug administration (Day 1) through the end of treatment period (Day 169)

ID	Title	Description
OG000	PLACEBO-IV-SC	Participants received either a fixed IV dose of placebo matching MEDI-551 on Days 1 and 15 or SC injection on Day 1.
OG001	MEDI-551 30 Mg-IV	Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.
OG002	MEDI-551 60 Mg-SC	Participants received SC injection of 60 mg MEDI-551 on Day 1.
OG003	MEDI-551 100 Mg-IV	Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15.

Secondary

Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-551

The time to reach the maximum observed serum concentration of MEDI-551.

Safety Population

Posted

Median

Full Range

Day

Predose (Day 1) and Postdose (IV Cohorts only), Days 4 (SC Cohorts only), 8, 15 Predose and Postdose (IV Cohorts only), 29, 57, 85, 113, 141, and 169

ID	Title	Description
OG000	MEDI-551 30 Mg-IV	Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.
OG001	MEDI-551 60 Mg-SC	Participants received SC injection of 60 mg MEDI-551 on Day 1.
OG002	MEDI-551 100 Mg-IV	Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15.
OG003	MEDI-551 300 Mg-SC	Participants received SC injection of 300 mg MEDI-551 on Day 1.
OG004	MEDI-551 600 Mg-IV

Secondary

Maximum Observed Serum Concentration (Cmax) of MEDI-551

The maximum observed serum concentration (Cmax) of MEDI-551.

Safety Population

Posted

Mean

Standard Deviation

microgram per milliliter (mcg/mL)

Predose (Day 1) and Postdose (IV Cohorts only), Days 4 (SC Cohorts only), 8, 15 Predose and Postdose (IV Cohorts only), 29, 57, 85, 113, 141, and 169

ID	Title	Description
OG000	MEDI-551 30 Mg-IV	Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.
OG001	MEDI-551 60 Mg-SC	Participants received SC injection of 60 mg MEDI-551 on Day 1.
OG002	MEDI-551 100 Mg-IV	Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15.
OG003	MEDI-551 300 Mg-SC	Participants received SC injection of 300 mg MEDI-551 on Day 1.
OG004

Secondary

Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC 0-last) of MEDI-551

The area under the concentration time curve from time 0 (dosing time) to the last measurable concentration (AUC 0-last) of MEDI-551.

Safety Population

Posted

Mean

Standard Deviation

microgram*day per milliliter(mcg*day/mL)

Predose (Day 1) and Postdose (IV Cohorts only), Days 4 (SC Cohorts only), 8, 15 Predose and Postdose (IV Cohorts only), 29, 57, 85, 113, 141, and 169

ID	Title	Description
OG000	MEDI-551 30 Mg-IV	Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.
OG001	MEDI-551 60 Mg-SC	Participants received SC injection of 60 mg MEDI-551 on Day 1.
OG002	MEDI-551 100 Mg-IV	Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15.
OG003	MEDI-551 300 Mg-SC	Participants received SC injection of 300 mg MEDI-551 on Day 1.

Secondary

Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC 0-infinity) of MEDI-551

The area under the concentration-time curve from dosing extrapolated to infinity (AUC 0-infinity) of MEDI-551.

Safety Population

Posted

Mean

Standard Deviation

mcg*day/mL

Predose (Day 1) and Postdose (IV Cohorts only), Days 4 (SC Cohorts only), 8, 15 Predose and Postdose (IV Cohorts only), 29, 57, 85, 113, 141, and 169

ID	Title	Description
OG000	MEDI-551 30 Mg-IV	Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.
OG001	MEDI-551 60 Mg-SC	Participants received SC injection of 60 mg MEDI-551 on Day 1.
OG002	MEDI-551 100 Mg-IV	Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15.
OG003	MEDI-551 300 Mg-SC	Participants received SC injection of 300 mg MEDI-551 on Day 1.

Secondary

Dose Normalized Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC 0-infinity/D) of MEDI-551

The AUC (0-infinity)/D is the area under concentration-time curve extrapolated to infinity post dose normalized by MEDI-551.

Safety Population

Posted

Mean

Standard Deviation

mcg*day/mL/mg

Predose (Day 1) and Postdose (IV Cohorts only), Days 4 (SC Cohorts only), 8, 15 Predose and Postdose (IV Cohorts only), 29, 57, 85, 113, 141, and 169

ID	Title	Description
OG000	MEDI-551 30 Mg-IV	Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.
OG001	MEDI-551 60 Mg-SC	Participants received SC injection of 60 mg MEDI-551 on Day 1.
OG002	MEDI-551 100 Mg-IV	Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15.
OG003	MEDI-551 300 Mg-SC	Participants received SC injection of 300 mg MEDI-551 on Day 1.

Secondary

Clearance of MEDI-551

Systemic clearance (CL) for MEDI-551 IV cohorts and apparent clearance (CL/F) for MEDI-551 SC cohorts were calculated

Safety Population

Posted

Mean

Standard Deviation

mL/day

Predose (Day 1) and Postdose (IV Cohorts only), Days 4 (SC Cohorts only), 8, 15 Predose and Postdose (IV Cohorts only), 29, 57, 85, 113, 141, and 169

ID	Title	Description
OG000	MEDI-551 30 Mg-IV	Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.
OG001	MEDI-551 60 Mg-SC	Participants received SC injection of 60 mg MEDI-551 on Day 1.
OG002	MEDI-551 100 Mg-IV	Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15.
OG003	MEDI-551 300 Mg-SC	Participants received SC injection of 300 mg MEDI-551 on Day 1.
OG004

Secondary

Terminal Elimination Half-life (t1/2) of MEDI-551

The terminal elimination half-life (t1/2) was estimated based on the plasma concentrations of MEDI-551.

Safety Population

Posted

Mean

Standard Deviation

Day

Predose (Day 1) and Postdose (IV Cohorts only), Days 4 (SC Cohorts only), 8, 15 Predose and Postdose (IV Cohorts only), 29, 57, 85, 113, 141, and 169

ID	Title	Description
OG000	MEDI-551 30 Mg-IV	Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.
OG001	MEDI-551 60 Mg-SC	Participants received SC injection of 60 mg MEDI-551 on Day 1.
OG002	MEDI-551 100 Mg-IV	Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15.
OG003	MEDI-551 300 Mg-SC	Participants received SC injection of 300 mg MEDI-551 on Day 1.
OG004

Secondary

Absolute Subcutaneous Bioavailability (F%) of MEDI-551

Bioavailability (F%) is the fraction of the study drug absorbed through non-intravenous administration compared with the corresponding intravenous administration of the same drug.

Safety Population

Posted

Number

Percentage of bioavailability

Predose (Day 1) and Days 4, 8, 15, 29, 57, 85, 113, 141, and 169

ID	Title	Description
OG000	MEDI-551 60 Mg-SC	Participants received SC injection of 60 mg MEDI-551 on Day 1.
OG001	MEDI-551 300 Mg-SC	Participants received SC injection of 300 mg MEDI-551 on Day 1.

Units	Counts
Participants	OG000

Secondary

Absolute CD20 B-cell Count at Baseline

Baseline absolute CD20 count is measured as the average between screening and predose on Day 1.

Safety Population

Posted

Mean

Standard Deviation

cells/mcL

Baseline (Days -28 to -1)

ID	Title	Description
OG000	PLACEBO-IV-SC	Participants received either a fixed IV dose of placebo matching MEDI-551 on Days 1 and 15 or SC injection on Day 1.
OG001	MEDI-551 30 Mg-IV	Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.
OG002	MEDI-551 60 Mg-SC	Participants received SC injection of 60 mg MEDI-551 on Day 1.
OG003	MEDI-551 100 Mg-IV	Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15.
OG004	MEDI-551 300 Mg-SC

Secondary

Time to 90 Percent (%) CD20 B-cell Depletion

Time in days of first observation where CD20 counts fall to or below 10 percent (%) of baseline.

Safety Population. No participants in placebo-IV-SC group reached 90% CD20 B-cell depletion.

Posted

Median

Full Range

Day

Baseline (Days -28 to -1) to long-term follow-up (LTFU) (Up to 18 months after EDV or 24 Week treatment period)

ID	Title	Description
OG000	PLACEBO-IV-SC	Participants received either a fixed IV dose of placebo matching MEDI-551 on Days 1 and 15 or SC injection on Day 1.
OG001	MEDI-551 30 Mg-IV	Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.
OG002	MEDI-551 60 Mg-SC	Participants received SC injection of 60 mg MEDI-551 on Day 1.
OG003	MEDI-551 100 Mg-IV	Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15.

Secondary

Duration of Suppression Greater Than or Equal to 90 % of CD20 B-cell Count

Time in days of last observation where CD20 counts remain at or below 10% of baseline. Participants whose samples are available were analyzed for this outcome measure.

Safety Population. No participants were included in placebo-IV-SC group since no participant reached 90% depletion.

Posted

Median

Full Range

Day

Baseline (Days -28 to -1) to LTFU (Up to 18 months after EDV or 24 Week treatment period)

ID	Title	Description
OG000	PLACEBO-IV-SC	Participants received either a fixed IV dose of placebo matching MEDI-551 on Days 1 and 15 or SC injection on Day 1.
OG001	MEDI-551 30 Mg-IV	Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.
OG002	MEDI-551 60 Mg-SC	Participants received SC injection of 60 mg MEDI-551 on Day 1.
OG003	MEDI-551 100 Mg-IV	Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15.

Secondary

Maximum Change From Baseline in Absolute CD20 of Peripheral Blood B-cell Count to LTFU

The maximum degree of depletion (intensity) measured during the course of the study for each participant by subtracting 100 from the lowest observed percent of baseline value.

Safety Population

Posted

Mean

Standard Deviation

Percentage of cells

Baseline (Days -28 to -1) to LTFU (Up to 18 months after EDV or 24 Week treatment period)

ID	Title	Description
OG000	PLACEBO-IV-SC	Participants received either a fixed IV dose of placebo matching MEDI-551 on Days 1 and 15 or SC injection on Day 1.
OG001	MEDI-551 30 Mg-IV	Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.
OG002	MEDI-551 60 Mg-SC	Participants received SC injection of 60 mg MEDI-551 on Day 1.
OG003	MEDI-551 100 Mg-IV	Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15.

Secondary

Number of Participants Positive for Anti-Drug Antibodies to MEDI-551

A participant was considered anti-drug antibody positive across the study if they had a positive reading at any time point during the study.

Safety Population

Posted

Count of Participants

Participants

Days 1, 29, 85 and 169

ID	Title	Description
OG000	PLACEBO-IV-SC	Participants received either a fixed IV dose of placebo matching MEDI-551 on Days 1 and 15 or SC injection on Day 1.
OG001	MEDI-551 30 Mg-IV	Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.
OG002	MEDI-551 60 Mg-SC	Participants received SC injection of 60 mg MEDI-551 on Day 1.
OG003	MEDI-551 100 Mg-IV	Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15.
OG004

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	PLACEBO-IV-SC	Participants received either a fixed IV dose of placebo matching MEDI-551 on Days 1 and 15 or SC injection on Day 1.	1	7	5	7
EG001	MEDI-551 60 Mg-SC	Participants received SC injection of 60 mg MEDI-551 on Day 1.	0	3	3	3
EG002	MEDI-551 100 Mg-IV	Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15.	0	4	3	4
EG003	MEDI-551 300 Mg-SC	Participants received SC injection of 300 mg MEDI-551 on Day 1.	1	3	2	3
EG004	MEDI-551 30 Mg-IV	Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.	1	5	4	5
EG005	MEDI-551 600 Mg-IV	Participants received a fixed IV dose of 600 mg MEDI-551 infused on Days 1 and 15.	1	6	6	6

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pyrexia	General disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected4 at risk EG0031 events1 affected3 at risk EG0040 events0 affected5 at risk EG0050 events0 affected6 at risk
Urinary tract infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected4 at risk EG003
Accidental overdose	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected4 at risk EG003
Multiple sclerosis relapse	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected4 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Asthenia	General disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected4 at risk EG0031 events1 affected3 at risk EG0040 events0 affected5 at risk EG0050 events0 affected6 at risk
Gait disturbance	General disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected4 at risk EG003
Pyrexia	General disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected3 at risk EG0021 events1 affected4 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0023 events2 affected4 at risk EG003
Oral herpes	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0025 events2 affected4 at risk EG003
Sinusitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected4 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected3 at risk EG0023 events2 affected4 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected3 at risk EG0020 events0 affected4 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0008 events2 affected7 at risk EG0010 events0 affected3 at risk EG0023 events1 affected4 at risk EG003
Blood pressure increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0002 events1 affected7 at risk EG0011 events1 affected3 at risk EG0020 events0 affected4 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected4 at risk EG003
Headache	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected4 at risk EG003
Multiple sclerosis relapse	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected4 at risk EG003
Urinary tract inflammation	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0022 events1 affected4 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected3 at risk EG0021 events1 affected4 at risk EG003

ID	Term
D009103	Multiple Sclerosis
D009165	Mycobacterium Infections, Nontuberculous

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
D009164	Mycobacterium Infections
D000193	Actinomycetales Infections
D016908	Gram-Positive Bacterial Infections
D001424	Bacterial Infections
D001423	Bacterial Infections and Mycoses
D007239	Infections