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Clinical Trial Results:
A Randomized, Blinded, Parallel-Group, Phase 2 Study Exploring the Safety, Tolerability, and Efficacy of Multiple Regimens of Natalizumab in Adult Subjects With Relapsing Multiple Sclerosis

Summary
EudraCT number	2010-024000-10
Trial protocol	BE DE ES IT
Global end of trial date	03 Oct 2014

Results information
Results version number	v1(current)
This version publication date	04 Feb 2016
First version publication date	15 Jul 2015
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

101MS206

ISRCTN number

US NCT number

NCT01405820

WHO universal trial number (UTN)

Sponsor organisation name

Biogen

Sponsor organisation address

225 Binney Street, Cambridge, United States, 02142

Public contact

Biogen Study Medical Director, Biogen, clinicaltrials@biogen.com

Scientific contact

Biogen Study Medical Director, Biogen, clinicaltrials@biogen.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

03 Oct 2014

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

03 Oct 2014

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this study was to explore the effects of multiple regimens of natalizumab on disease activity and safety in participants with relapsing-remitting Multiple Sclerosis (RRMS).

Protection of trial subjects

Written informed consent was obtained from each subject prior to evaluations being performed for eligibility. Subjects were given adequate time to review the information in the informed consent and were allowed to ask, and have answered, questions concerning all portions of the conduct of the study. Through the informed consent process each participant was made aware of the purpose of the study, the procedures, the benefits and risks of the study, the discomforts and the precautions taken. Any side effects or other health issues occurring during the study were followed up by the study doctor. Participants were able to stop taking part in the study at any time without giving any reason.

Background therapy

Evidence for comparator

Actual start date of recruitment

01 Aug 2011

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Germany: 71

Country: Number of subjects enrolled

France: 57

Country: Number of subjects enrolled

Spain: 45

Country: Number of subjects enrolled

Belgium: 8

Country: Number of subjects enrolled

Italy: 109

Worldwide total number of subjects

290

EEA total number of subjects

290

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

290

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Subject eligibility for the study was determined within approximately 4 weeks prior to study entry.

Period 1 title

Randomized Treatment Period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Natalizumab 300 mg IV every 4 weeks

Arm description

Natalizumab 300 mg intravenous (IV) every 4 weeks for 60 weeks.

Arm type

Active comparator

Investigational medicinal product name

Natalizumab for IV Infusion

Investigational medicinal product code

BG00002

Other name

Tysabri

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

All subjects received study treatment every 4 weeks. Subjects receiving natalizumab every 12 weeks received matching placebo during the intervening 4-week periods.

Natalizumab 300 mg SC every 4 weeks

Arm description

Natalizumab 300 mg subcutaneous (SC) every 4 weeks for 60 weeks.

Arm type

Experimental

Investigational medicinal product name

Natalizumab for SC Injection

Investigational medicinal product code

BG00002

Other name

Tysabri

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

All subjects received study treatment every 4 weeks. Subjects receiving natalizumab every 12 weeks received matching placebo during the intervening 4-week periods.

Natalizumab 300 mg IV every 12 weeks

Arm description

Natalizumab 300 mg IV every 12 weeks for 60 weeks with matching IV placebo administered during the intervening 4-week periods.

Arm type

Experimental

Investigational medicinal product name

Natalizumab for IV Infusion

Investigational medicinal product code

BG00002

Other name

Tysabri

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

All subjects received study treatment every 4 weeks. Subjects receiving natalizumab every 12 weeks received matching placebo during the intervening 4-week periods.

Investigational medicinal product name

IV Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

All subjects received study treatment every 4 weeks. Subjects receiving natalizumab every 12 weeks received matching placebo during the intervening 4-week periods.

Natalizumab 300 mg SC every 12 weeks

Arm description

Natalizumab 300 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods.

Arm type

Experimental

Investigational medicinal product name

SC Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

All subjects received study treatment every 4 weeks. Subjects receiving natalizumab every 12 weeks received matching placebo during the intervening 4-week periods.

Investigational medicinal product name

Natalizumab for SC Injection

Investigational medicinal product code

BG00002

Other name

Tysabri

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

All subjects received study treatment every 4 weeks. Subjects receiving natalizumab every 12 weeks received matching placebo during the intervening 4-week periods.

Natalizumab 150 mg IV every 12 weeks

Arm description

Natalizumab 150 mg IV every 12 weeks for 60 weeks with matching IV placebo administered during the intervening 4-week periods.

Arm type

Experimental

Investigational medicinal product name

Natalizumab for IV Infusion

Investigational medicinal product code

BG00002

Other name

Tysabri

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

All subjects received study treatment every 4 weeks. Subjects receiving natalizumab every 12 weeks received matching placebo during the intervening 4-week periods.

Investigational medicinal product name

IV Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

All subjects received study treatment every 4 weeks. Subjects receiving natalizumab every 12 weeks received matching placebo during the intervening 4-week periods.

Natalizumab 150 mg SC every 12 weeks

Arm description

Natalizumab 150 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods.

Arm type

Experimental

Investigational medicinal product name

Natalizumab for SC Injection

Investigational medicinal product code

BG00002

Other name

Tysabri

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

All subjects received study treatment every 4 weeks. Subjects receiving natalizumab every 12 weeks received matching placebo during the intervening 4-week periods.

Investigational medicinal product name

SC Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

All subjects received study treatment every 4 weeks. Subjects receiving natalizumab every 12 weeks received matching placebo during the intervening 4-week periods.

Number of subjects in period 1	Natalizumab 300 mg IV every 4 weeks	Natalizumab 300 mg SC every 4 weeks	Natalizumab 300 mg IV every 12 weeks	Natalizumab 300 mg SC every 12 weeks	Natalizumab 150 mg IV every 12 weeks	Natalizumab 150 mg SC every 12 weeks
Started	54	45	52	54	47	38
Completed	43	35	9	3	2	1
Not completed	11	10	43	51	45	37
Withdrew prior to dosing	-	-	-	1	-	-
Adverse event, serious fatal	-	-	-	1	-	-
Consent withdrawn by subject	6	2	2	2	-	-
Physician decision	-	2	1	-	-	-
Adverse event, non-fatal	3	3	3	-	2	1
Incorrect study treatment	-	-	3	-	2	-
Not Specified	2	2	1	1	-	-
Treatment arm closed	-	-	20	36	33	28
Rescue	-	1	13	10	8	8

Period 2 title

Open-Label Treatment Period

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Natalizumab 300 mg IV every 4 weeks

Arm description

Natalizumab 300 mg IV every 4 weeks for 60 weeks. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.

Arm type

Experimental

Investigational medicinal product name

Natalizumab for IV Infusion

Investigational medicinal product code

BG00002

Other name

Tysabri

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

All subjects received study treatment every 4 weeks.

Natalizumab 300 mg SC every 4 weeks

Arm description

Natalizumab 300 mg SC every 4 weeks for 60 weeks. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.

Arm type

Experimental

Investigational medicinal product name

Natalizumab for IV Infusion

Investigational medicinal product code

BG00002

Other name

Tysabri

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

All subjects received study treatment every 4 weeks.

Natalizumab 300 mg IV every 12 weeks

Arm description

Natalizumab 300 mg IV every 12 weeks for 60 weeks with matching IV placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.

Arm type

Experimental

Investigational medicinal product name

Natalizumab for IV Infusion

Investigational medicinal product code

BG00002

Other name

Tysabri

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

All subjects received study treatment every 4 weeks.

Natalizumab 300 mg SC every 12 weeks

Arm description

Natalizumab 300 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.

Arm type

Experimental

Investigational medicinal product name

Natalizumab for IV Infusion

Investigational medicinal product code

BG00002

Other name

Tysabri

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

All subjects received study treatment every 4 weeks.

Natalizumab 150 mg IV every 12 weeks

Arm description

Natalizumab 150 mg IV every 12 weeks for 60 weeks with matching IV placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.

Arm type

Experimental

Investigational medicinal product name

Natalizumab for IV Infusion

Investigational medicinal product code

BG00002

Other name

Tysabri

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

All subjects received study treatment every 4 weeks.

Natalizumab 150 mg SC every 12 weeks

Arm description

Natalizumab 150 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.

Arm type

Experimental

Investigational medicinal product name

Natalizumab for Subcutaneous Injection

Investigational medicinal product code

BG00002

Other name

Tysabri

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

All subjects received study treatment every 4 weeks. Subjects receiving natalizumab every 12 weeks received matching placebo during the intervening 4-week periods.

Investigational medicinal product name

SC Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

All subjects received study treatment every 4 weeks. Subjects receiving natalizumab every 12 weeks received matching placebo during the intervening 4-week periods.

Number of subjects in period 2	Natalizumab 300 mg IV every 4 weeks	Natalizumab 300 mg SC every 4 weeks	Natalizumab 300 mg IV every 12 weeks	Natalizumab 300 mg SC every 12 weeks	Natalizumab 150 mg IV every 12 weeks	Natalizumab 150 mg SC every 12 weeks
Started	44	35	42	42	42	32
Completed	40	33	39	37	40	30
Not completed	4	2	3	5	2	2
Consent withdrawn by subject	3	1	1	1	-	1
Physician decision	-	-	1	2	1	-
Adverse event, non-fatal	-	-	-	1	-	-
Not Specified	1	1	1	1	1	1

Baseline characteristics

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Reporting group title

Natalizumab 300 mg IV every 4 weeks

Reporting group description

Natalizumab 300 mg intravenous (IV) every 4 weeks for 60 weeks.

Reporting group title

Natalizumab 300 mg SC every 4 weeks

Reporting group description

Natalizumab 300 mg subcutaneous (SC) every 4 weeks for 60 weeks.

Reporting group title

Natalizumab 300 mg IV every 12 weeks

Reporting group description

Natalizumab 300 mg IV every 12 weeks for 60 weeks with matching IV placebo administered during the intervening 4-week periods.

Reporting group title

Natalizumab 300 mg SC every 12 weeks

Reporting group description

Natalizumab 300 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods.

Reporting group title

Natalizumab 150 mg IV every 12 weeks

Reporting group description

Natalizumab 150 mg IV every 12 weeks for 60 weeks with matching IV placebo administered during the intervening 4-week periods.

Reporting group title

Natalizumab 150 mg SC every 12 weeks

Reporting group description

Natalizumab 150 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods.

Reporting group values	Natalizumab 300 mg IV every 4 weeks	Natalizumab 300 mg SC every 4 weeks	Natalizumab 300 mg IV every 12 weeks	Natalizumab 300 mg SC every 12 weeks	Natalizumab 150 mg IV every 12 weeks	Natalizumab 150 mg SC every 12 weeks	Total
Number of subjects	54	45	52	54	47	38	290
Age, Customized
Units: participants
18 to 19 years	0	1	0	0	0	0	1
20 to 29 years	7	11	7	7	5	11	48
30 to 39 years	22	15	21	24	21	14	117
40 to 49 years	20	16	17	17	16	9	95
50 to 56 years	5	2	7	6	5	4	29
Age Continuous
Units: years
arithmetic mean (standard deviation)	38.4 ( 7.84 )	36.3 ( 8.92 )	38.7 ( 8.43 )	38.7 ( 7.85 )	38.7 ( 8.61 )	36 ( 9.03 )	-
Gender, Male/Female
Units: participants
Female	39	29	37	41	34	24	204
Male	15	16	15	13	13	14	86

End points

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Reporting group title

Natalizumab 300 mg IV every 4 weeks

Reporting group description

Natalizumab 300 mg intravenous (IV) every 4 weeks for 60 weeks.

Reporting group title

Natalizumab 300 mg SC every 4 weeks

Reporting group description

Natalizumab 300 mg subcutaneous (SC) every 4 weeks for 60 weeks.

Reporting group title

Natalizumab 300 mg IV every 12 weeks

Reporting group description

Natalizumab 300 mg IV every 12 weeks for 60 weeks with matching IV placebo administered during the intervening 4-week periods.

Reporting group title

Natalizumab 300 mg SC every 12 weeks

Reporting group description

Natalizumab 300 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods.

Reporting group title

Natalizumab 150 mg IV every 12 weeks

Reporting group description

Natalizumab 150 mg IV every 12 weeks for 60 weeks with matching IV placebo administered during the intervening 4-week periods.

Reporting group title

Natalizumab 150 mg SC every 12 weeks

Reporting group description

Natalizumab 150 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods.

Reporting group title

Natalizumab 300 mg IV every 4 weeks

Reporting group description

Natalizumab 300 mg IV every 4 weeks for 60 weeks. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.

Reporting group title

Natalizumab 300 mg SC every 4 weeks

Reporting group description

Natalizumab 300 mg SC every 4 weeks for 60 weeks. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.

Reporting group title

Natalizumab 300 mg IV every 12 weeks

Reporting group description

Natalizumab 300 mg IV every 12 weeks for 60 weeks with matching IV placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.

Reporting group title

Natalizumab 300 mg SC every 12 weeks

Reporting group description

Natalizumab 300 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.

Reporting group title

Natalizumab 150 mg IV every 12 weeks

Reporting group description

Natalizumab 150 mg IV every 12 weeks for 60 weeks with matching IV placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.

Reporting group title

Natalizumab 150 mg SC every 12 weeks

Reporting group description

Natalizumab 150 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.

Primary: Cumulative Number of Combined Unique Active Lesions

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End point title

Cumulative Number of Combined Unique Active Lesions ^[1]

End point description

Cumulative number of combined unique active lesions (sum of the number of new gadolinium (Gd)-enhancing lesions and new or newly enlarging T2 hyperintense lesions not associated with Gd-enhancement on T1 weighted scans) based on brain magnetic resonance imaging (MRI) scans up to Week 60. Modified intent-to-treat (mITT) population: all randomized subjects who received at least 1 dose of study drug, had at least 1 efficacy assessment, and had no statistical protocol deviations.

End point type

Primary

End point timeframe

Up to Week 60

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were planned for this endpoint, and are presented here.

End point values	Natalizumab 300 mg IV every 4 weeks	Natalizumab 300 mg SC every 4 weeks	Natalizumab 300 mg IV every 12 weeks	Natalizumab 300 mg SC every 12 weeks	Natalizumab 150 mg IV every 12 weeks	Natalizumab 150 mg SC every 12 weeks
Number of subjects analysed	52	44	45	50	35	32
Units: lesions
arithmetic mean (standard deviation)	0.23 ( 1.262 )	0.02 ( 0.151 )	3.84 ( 8.054 )	3.08 ( 8.216 )	6.09 ( 15.424 )	6.44 ( 11.285 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

AEs were analyzed during the randomized and open-label periods separately. Randomized period: AEs, after 1st randomized dose on Day 0 and prior to open-label infusion of natalizumab at Week 60 (±5 days); SAEs also between Screening and dosing on Day 0.

Adverse event reporting additional description

Open-label period: on or after open-label infusion of natalizumab at Week 60 through to Week 72 (±2 weeks). If participant did not receive natalizumab infusions during the open-label period (Week 60 to Week 72), all events with an onset date after Day 0 were considered as occurring during the randomized treatment period.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

16.1

Reporting group title

Randomized Period: Natalizumab 300 mg IV every 4 weeks

Reporting group description

Natalizumab 300 mg IV every 4 weeks for 60 weeks.

Reporting group title

Randomized Period: Natalizumab 300 mg SC every 4 weeks

Reporting group description

Natalizumab 300 mg SC every 4 weeks for 60 weeks.

Reporting group title

Randomized Period: Natalizumab 300 mg IV every 12 weeks

Reporting group description

Natalizumab 300 mg IV every 12 weeks for 60 weeks with matching IV placebo administered during the intervening 4-week periods.

Reporting group title

Randomized Period: Natalizumab 300 mg SC every 12 weeks

Reporting group description

Natalizumab 300 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods.

Reporting group title

Randomized Period: Natalizumab 150 mg IV every 12 weeks

Reporting group description

Natalizumab 150 mg IV every 12 weeks for 60 weeks with matching IV placebo administered during the intervening 4-week periods.

Reporting group title

Randomized Period: Natalizumab 150 mg SC every 12 weeks

Reporting group description

Natalizumab 150 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods.

Reporting group title

Open-label Period: Natalizumab 300 mg IV every 4 weeks

Reporting group description

Natalizumab 300 mg IV every 4 weeks for 60 weeks. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.

Reporting group title

Open-label Period: Natalizumab 300 mg SC every 4 weeks

Reporting group description

Natalizumab 300 mg SC every 4 weeks for 60 weeks. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.

Reporting group title

Open-label Period: Natalizumab 300 mg IV every 12 weeks

Reporting group description

Natalizumab 300 mg IV every 12 weeks for 60 weeks with matching IV placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.

Reporting group title

Open-label Period: Natalizumab 300 mg SC every 12 weeks

Reporting group description

Natalizumab 300 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.

Reporting group title

Open-label Period: Natalizumab 150 mg IV every 12 weeks

Reporting group description

Natalizumab 150 mg IV every 12 weeks for 60 weeks with matching IV placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.

Reporting group title

Open-label Period: Natalizumab 150 mg SC every 12 weeks

Reporting group description

Natalizumab 150 mg SC every 12 weeks for 60 weeks with matching SC placebo administered during the intervening 4-week periods. Open-label natalizumab treatment 300 mg IV at Weeks 60, 64, and 68.

Randomized Period: Natalizumab 300 mg IV every 4 weeks

Randomized Period: Natalizumab 300 mg SC every 4 weeks

Randomized Period: Natalizumab 300 mg IV every 12 weeks

Randomized Period: Natalizumab 300 mg SC every 12 weeks

Randomized Period: Natalizumab 150 mg IV every 12 weeks

Randomized Period: Natalizumab 150 mg SC every 12 weeks

Open-label Period: Natalizumab 300 mg IV every 4 weeks

Open-label Period: Natalizumab 300 mg SC every 4 weeks

Open-label Period: Natalizumab 300 mg IV every 12 weeks

Open-label Period: Natalizumab 300 mg SC every 12 weeks

Open-label Period: Natalizumab 150 mg IV every 12 weeks

Open-label Period: Natalizumab 150 mg SC every 12 weeks

Total subjects affected by serious adverse events

subjects affected / exposed

7 / 54 (12.96%)

4 / 45 (8.89%)

4 / 52 (7.69%)

3 / 53 (5.66%)

4 / 47 (8.51%)

1 / 38 (2.63%)

0 / 44 (0.00%)

1 / 35 (2.86%)

0 / 42 (0.00%)

1 / 42 (2.38%)

2 / 32 (6.25%)

number of deaths (all causes)

number of deaths resulting from adverse events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Carcinoma In Situ

subjects affected / exposed

0 / 54 (0.00%)

0 / 45 (0.00%)

1 / 52 (1.92%)

0 / 53 (0.00%)

0 / 47 (0.00%)

0 / 38 (0.00%)

0 / 44 (0.00%)

0 / 35 (0.00%)

0 / 42 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lung Adenocarcinoma Metastatic

subjects affected / exposed

0 / 54 (0.00%)

0 / 45 (0.00%)

0 / 52 (0.00%)

1 / 53 (1.89%)

0 / 47 (0.00%)

0 / 38 (0.00%)

0 / 44 (0.00%)

0 / 35 (0.00%)

0 / 42 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Investigations

Nuclear Magnetic Resonance Imaging Abnormal

subjects affected / exposed

0 / 54 (0.00%)

0 / 45 (0.00%)

1 / 52 (1.92%)

0 / 53 (0.00%)

0 / 47 (0.00%)

0 / 38 (0.00%)

0 / 44 (0.00%)

0 / 35 (0.00%)

0 / 42 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Fall

subjects affected / exposed

0 / 54 (0.00%)

0 / 45 (0.00%)

0 / 52 (0.00%)

1 / 53 (1.89%)

0 / 47 (0.00%)

0 / 38 (0.00%)

0 / 44 (0.00%)

0 / 35 (0.00%)

0 / 42 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Radius Fracture

subjects affected / exposed

0 / 54 (0.00%)

0 / 45 (0.00%)

0 / 52 (0.00%)

1 / 53 (1.89%)

0 / 47 (0.00%)

0 / 38 (0.00%)

0 / 44 (0.00%)

0 / 35 (0.00%)

0 / 42 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Multiple Sclerosis Relapse

subjects affected / exposed

1 / 54 (1.85%)

2 / 45 (4.44%)

1 / 52 (1.92%)

0 / 53 (0.00%)

2 / 47 (4.26%)

0 / 38 (0.00%)

0 / 44 (0.00%)

0 / 35 (0.00%)

0 / 42 (0.00%)

1 / 42 (2.38%)

2 / 32 (6.25%)

occurrences causally related to treatment / all

0 / 1

1 / 2

1 / 1

0 / 0

1 / 2

0 / 0

0 / 1

1 / 1

2 / 2

deaths causally related to treatment / all

0 / 0

Epilepsy

subjects affected / exposed

1 / 54 (1.85%)

0 / 45 (0.00%)

0 / 52 (0.00%)

0 / 53 (0.00%)

1 / 47 (2.13%)

0 / 38 (0.00%)

0 / 44 (0.00%)

0 / 35 (0.00%)

0 / 42 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cerebrovascular Insufficiency

subjects affected / exposed

0 / 54 (0.00%)

0 / 45 (0.00%)

0 / 52 (0.00%)

1 / 53 (1.89%)

0 / 47 (0.00%)

0 / 38 (0.00%)

0 / 44 (0.00%)

0 / 35 (0.00%)

0 / 42 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Coma

subjects affected / exposed

0 / 54 (0.00%)

1 / 45 (2.22%)

0 / 52 (0.00%)

0 / 53 (0.00%)

0 / 47 (0.00%)

0 / 38 (0.00%)

0 / 44 (0.00%)

0 / 35 (0.00%)

0 / 42 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Polyneuropathy

subjects affected / exposed

0 / 54 (0.00%)

0 / 45 (0.00%)

1 / 52 (1.92%)

0 / 53 (0.00%)

0 / 47 (0.00%)

0 / 38 (0.00%)

0 / 44 (0.00%)

0 / 35 (0.00%)

0 / 42 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Vomiting

subjects affected / exposed

1 / 54 (1.85%)

0 / 45 (0.00%)

0 / 52 (0.00%)

0 / 53 (0.00%)

0 / 47 (0.00%)

0 / 38 (0.00%)

0 / 44 (0.00%)

0 / 35 (0.00%)

0 / 42 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Abdominal Pain

subjects affected / exposed

0 / 54 (0.00%)

0 / 45 (0.00%)

0 / 52 (0.00%)

0 / 53 (0.00%)

0 / 47 (0.00%)

0 / 38 (0.00%)

0 / 44 (0.00%)

1 / 35 (2.86%)

0 / 42 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

Bipolar I Disorder

subjects affected / exposed

1 / 54 (1.85%)

0 / 45 (0.00%)

0 / 52 (0.00%)

0 / 53 (0.00%)

0 / 47 (0.00%)

0 / 38 (0.00%)

0 / 44 (0.00%)

0 / 35 (0.00%)

0 / 42 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pathological Gambling

subjects affected / exposed

1 / 54 (1.85%)

0 / 45 (0.00%)

0 / 52 (0.00%)

0 / 53 (0.00%)

0 / 47 (0.00%)

0 / 38 (0.00%)

0 / 44 (0.00%)

0 / 35 (0.00%)

0 / 42 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Automatic Bladder

subjects affected / exposed

1 / 54 (1.85%)

0 / 45 (0.00%)

0 / 52 (0.00%)

0 / 53 (0.00%)

0 / 47 (0.00%)

0 / 38 (0.00%)

0 / 44 (0.00%)

0 / 35 (0.00%)

0 / 42 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary Retention

subjects affected / exposed

1 / 54 (1.85%)

0 / 45 (0.00%)

0 / 52 (0.00%)

0 / 53 (0.00%)

0 / 47 (0.00%)

0 / 38 (0.00%)

0 / 44 (0.00%)

0 / 35 (0.00%)

0 / 42 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Intervertebral Disc Protrusion

subjects affected / exposed

1 / 54 (1.85%)

0 / 45 (0.00%)

0 / 52 (0.00%)

0 / 53 (0.00%)

0 / 47 (0.00%)

0 / 38 (0.00%)

0 / 44 (0.00%)

0 / 35 (0.00%)

0 / 42 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Appendicitis

subjects affected / exposed

0 / 54 (0.00%)

1 / 45 (2.22%)

0 / 52 (0.00%)

0 / 53 (0.00%)

0 / 47 (0.00%)

0 / 38 (0.00%)

0 / 44 (0.00%)

0 / 35 (0.00%)

0 / 42 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Escherichia Urinary Tract Infection

subjects affected / exposed

0 / 54 (0.00%)

0 / 45 (0.00%)

0 / 52 (0.00%)

0 / 53 (0.00%)

1 / 47 (2.13%)

0 / 38 (0.00%)

0 / 44 (0.00%)

0 / 35 (0.00%)

0 / 42 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Meningitis Enteroviral

subjects affected / exposed

0 / 54 (0.00%)

0 / 45 (0.00%)

1 / 52 (1.92%)

0 / 53 (0.00%)

0 / 47 (0.00%)

0 / 38 (0.00%)

0 / 44 (0.00%)

0 / 35 (0.00%)

0 / 42 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Progressive Multifocal Leukoencephalopathy

subjects affected / exposed

1 / 54 (1.85%)

0 / 45 (0.00%)

0 / 52 (0.00%)

0 / 53 (0.00%)

0 / 47 (0.00%)

0 / 38 (0.00%)

0 / 44 (0.00%)

0 / 35 (0.00%)

0 / 42 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urosepsis

subjects affected / exposed

0 / 54 (0.00%)

0 / 45 (0.00%)

0 / 52 (0.00%)

0 / 53 (0.00%)

0 / 47 (0.00%)

1 / 38 (2.63%)

0 / 44 (0.00%)

0 / 35 (0.00%)

0 / 42 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bronchitis

subjects affected / exposed

0 / 54 (0.00%)

0 / 45 (0.00%)

0 / 52 (0.00%)

0 / 53 (0.00%)

0 / 47 (0.00%)

0 / 38 (0.00%)

0 / 44 (0.00%)

1 / 35 (2.86%)

0 / 42 (0.00%)

0 / 32 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Randomized Period: Natalizumab 300 mg IV every 4 weeks	Randomized Period: Natalizumab 300 mg SC every 4 weeks	Randomized Period: Natalizumab 300 mg IV every 12 weeks	Randomized Period: Natalizumab 300 mg SC every 12 weeks	Randomized Period: Natalizumab 150 mg IV every 12 weeks	Randomized Period: Natalizumab 150 mg SC every 12 weeks	Open-label Period: Natalizumab 300 mg IV every 4 weeks	Open-label Period: Natalizumab 300 mg SC every 4 weeks	Open-label Period: Natalizumab 300 mg IV every 12 weeks	Open-label Period: Natalizumab 300 mg SC every 12 weeks	Open-label Period: Natalizumab 150 mg IV every 12 weeks	Open-label Period: Natalizumab 150 mg SC every 12 weeks
Total subjects affected by non serious adverse events
subjects affected / exposed	40 / 54 (74.07%)	31 / 45 (68.89%)	31 / 52 (59.62%)	34 / 53 (64.15%)	31 / 47 (65.96%)	17 / 38 (44.74%)	2 / 44 (4.55%)	4 / 35 (11.43%)	2 / 42 (4.76%)	0 / 42 (0.00%)	4 / 42 (9.52%)	6 / 32 (18.75%)
Investigations
Nuclear Magnetic Resonance Imaging Abnormal
subjects affected / exposed	0 / 54 (0.00%)	0 / 45 (0.00%)	0 / 52 (0.00%)	1 / 53 (1.89%)	0 / 47 (0.00%)	2 / 38 (5.26%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	0	0	1	0	2	0	0	0	0	0	0
Vascular disorders
Hypotension
subjects affected / exposed	0 / 54 (0.00%)	1 / 45 (2.22%)	3 / 52 (5.77%)	0 / 53 (0.00%)	0 / 47 (0.00%)	0 / 38 (0.00%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	1	3	0	0	0	0	0	0	0	0	0
Nervous system disorders
Multiple Sclerosis Relapse
subjects affected / exposed	8 / 54 (14.81%)	6 / 45 (13.33%)	13 / 52 (25.00%)	17 / 53 (32.08%)	12 / 47 (25.53%)	5 / 38 (13.16%)	0 / 44 (0.00%)	0 / 35 (0.00%)	1 / 42 (2.38%)	0 / 42 (0.00%)	3 / 42 (7.14%)	2 / 32 (6.25%)
occurrences all number	9	6	14	18	15	5	0	0	1	0	3	2
Headache
subjects affected / exposed	4 / 54 (7.41%)	9 / 45 (20.00%)	7 / 52 (13.46%)	5 / 53 (9.43%)	3 / 47 (6.38%)	4 / 38 (10.53%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	7	12	18	6	4	5	0	0	0	0	0	0
Paraesthesia
subjects affected / exposed	2 / 54 (3.70%)	1 / 45 (2.22%)	2 / 52 (3.85%)	3 / 53 (5.66%)	0 / 47 (0.00%)	0 / 38 (0.00%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	3	2	2	4	0	0	0	0	0	0	0	0
Sciatica
subjects affected / exposed	1 / 54 (1.85%)	1 / 45 (2.22%)	3 / 52 (5.77%)	0 / 53 (0.00%)	0 / 47 (0.00%)	0 / 38 (0.00%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	1	2	3	0	0	0	0	0	0	0	0	0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	6 / 54 (11.11%)	6 / 45 (13.33%)	4 / 52 (7.69%)	1 / 53 (1.89%)	2 / 47 (4.26%)	1 / 38 (2.63%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	6	6	4	1	2	1	0	0	0	0	0	0
Injection Site Pain
subjects affected / exposed	0 / 54 (0.00%)	1 / 45 (2.22%)	0 / 52 (0.00%)	3 / 53 (5.66%)	0 / 47 (0.00%)	3 / 38 (7.89%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	4	0	7	0	7	0	0	0	0	0	0
Pyrexia
subjects affected / exposed	0 / 54 (0.00%)	1 / 45 (2.22%)	0 / 52 (0.00%)	1 / 53 (1.89%)	3 / 47 (6.38%)	1 / 38 (2.63%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	2	0	1	3	1	0	0	0	0	0	0
Pain
subjects affected / exposed	0 / 54 (0.00%)	3 / 45 (6.67%)	0 / 52 (0.00%)	0 / 53 (0.00%)	0 / 47 (0.00%)	0 / 38 (0.00%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	0	4	0	0	0	0	0	0	0	0	0	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	4 / 54 (7.41%)	4 / 45 (8.89%)	2 / 52 (3.85%)	1 / 53 (1.89%)	4 / 47 (8.51%)	0 / 38 (0.00%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	4	5	2	1	4	0	0	0	0	0	0	0
Nausea
subjects affected / exposed	3 / 54 (5.56%)	4 / 45 (8.89%)	2 / 52 (3.85%)	2 / 53 (3.77%)	0 / 47 (0.00%)	0 / 38 (0.00%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	3	4	2	2	0	0	0	0	0	0	0	0
Vomiting
subjects affected / exposed	1 / 54 (1.85%)	4 / 45 (8.89%)	0 / 52 (0.00%)	2 / 53 (3.77%)	1 / 47 (2.13%)	0 / 38 (0.00%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	1	4	0	2	1	0	0	0	0	0	0	0
Constipation
subjects affected / exposed	2 / 54 (3.70%)	1 / 45 (2.22%)	0 / 52 (0.00%)	1 / 53 (1.89%)	3 / 47 (6.38%)	0 / 38 (0.00%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	2	1	0	1	3	0	0	0	0	0	0	0
Abdominal Pain
subjects affected / exposed	1 / 54 (1.85%)	4 / 45 (8.89%)	0 / 52 (0.00%)	1 / 53 (1.89%)	0 / 47 (0.00%)	0 / 38 (0.00%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	1	4	0	1	0	0	0	0	0	0	0	0
Toothache
subjects affected / exposed	4 / 54 (7.41%)	0 / 45 (0.00%)	0 / 52 (0.00%)	1 / 53 (1.89%)	0 / 47 (0.00%)	1 / 38 (2.63%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	7	0	0	1	0	1	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
subjects affected / exposed	2 / 54 (3.70%)	1 / 45 (2.22%)	1 / 52 (1.92%)	4 / 53 (7.55%)	0 / 47 (0.00%)	1 / 38 (2.63%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	2	1	1	4	0	1	0	0	0	0	0	0
Cough
subjects affected / exposed	3 / 54 (5.56%)	0 / 45 (0.00%)	0 / 52 (0.00%)	1 / 53 (1.89%)	0 / 47 (0.00%)	0 / 38 (0.00%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	4	0	0	2	0	0	0	0	0	0	0	0
Psychiatric disorders
Depression
subjects affected / exposed	1 / 54 (1.85%)	3 / 45 (6.67%)	2 / 52 (3.85%)	1 / 53 (1.89%)	0 / 47 (0.00%)	1 / 38 (2.63%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	1	3	2	1	0	1	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Back Pain
subjects affected / exposed	3 / 54 (5.56%)	2 / 45 (4.44%)	3 / 52 (5.77%)	1 / 53 (1.89%)	2 / 47 (4.26%)	1 / 38 (2.63%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	4	2	3	1	2	1	0	0	0	0	0	0
Pain in Extremity
subjects affected / exposed	2 / 54 (3.70%)	3 / 45 (6.67%)	2 / 52 (3.85%)	2 / 53 (3.77%)	2 / 47 (4.26%)	1 / 38 (2.63%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	2	3	2	3	2	1	0	0	0	0	0	0
Arthralgia
subjects affected / exposed	3 / 54 (5.56%)	4 / 45 (8.89%)	0 / 52 (0.00%)	1 / 53 (1.89%)	3 / 47 (6.38%)	0 / 38 (0.00%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	3	4	0	1	3	0	0	0	0	0	0	0
Infections and infestations
Nasopharyngitis
subjects affected / exposed	13 / 54 (24.07%)	8 / 45 (17.78%)	8 / 52 (15.38%)	9 / 53 (16.98%)	8 / 47 (17.02%)	4 / 38 (10.53%)	2 / 44 (4.55%)	1 / 35 (2.86%)	1 / 42 (2.38%)	0 / 42 (0.00%)	0 / 42 (0.00%)	2 / 32 (6.25%)
occurrences all number	19	8	14	16	8	4	2	1	1	0	0	2
Urinary Tract Infection
subjects affected / exposed	8 / 54 (14.81%)	5 / 45 (11.11%)	3 / 52 (5.77%)	4 / 53 (7.55%)	4 / 47 (8.51%)	1 / 38 (2.63%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	10	7	4	5	6	4	0	0	0	0	0	0
Influenza
subjects affected / exposed	4 / 54 (7.41%)	2 / 45 (4.44%)	1 / 52 (1.92%)	2 / 53 (3.77%)	8 / 47 (17.02%)	0 / 38 (0.00%)	0 / 44 (0.00%)	1 / 35 (2.86%)	0 / 42 (0.00%)	0 / 42 (0.00%)	1 / 42 (2.38%)	3 / 32 (9.38%)
occurrences all number	4	3	1	2	9	0	0	1	0	0	1	3
Pharyngitis
subjects affected / exposed	3 / 54 (5.56%)	1 / 45 (2.22%)	1 / 52 (1.92%)	1 / 53 (1.89%)	4 / 47 (8.51%)	1 / 38 (2.63%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	3	1	1	1	4	1	0	0	0	0	0	0
Bronchitis
subjects affected / exposed	2 / 54 (3.70%)	3 / 45 (6.67%)	0 / 52 (0.00%)	4 / 53 (7.55%)	0 / 47 (0.00%)	1 / 38 (2.63%)	0 / 44 (0.00%)	2 / 35 (5.71%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	2	5	0	4	0	1	0	2	0	0	0	0
Gastroenteritis
subjects affected / exposed	1 / 54 (1.85%)	3 / 45 (6.67%)	2 / 52 (3.85%)	2 / 53 (3.77%)	0 / 47 (0.00%)	1 / 38 (2.63%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	1	6	2	2	0	1	0	0	0	0	0	0
Sinusitis
subjects affected / exposed	2 / 54 (3.70%)	0 / 45 (0.00%)	3 / 52 (5.77%)	2 / 53 (3.77%)	2 / 47 (4.26%)	0 / 38 (0.00%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	3	0	4	2	2	0	0	0	0	0	0	0
Oral Herpes
subjects affected / exposed	4 / 54 (7.41%)	1 / 45 (2.22%)	0 / 52 (0.00%)	1 / 53 (1.89%)	1 / 47 (2.13%)	0 / 38 (0.00%)	0 / 44 (0.00%)	0 / 35 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 42 (0.00%)	0 / 32 (0.00%)
occurrences all number	6	1	0	1	2	0	0	0	0	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

03 Mar 2011

The primary reason for this amendment was the addition of optional exploratory pharmacogenomic analysis using DNA samples derived from whole blood collected at Baseline. The purpose of the analysis was to explore identification of genetic variation associated with study treatment response and to explore host genetic mutations that may increase individual subjects’ susceptibility or resistance to developing PML.

28 Feb 2012

The primary reason for this amendment was to align the safety information in the protocol related to the risk factors for the development of PML with the established risk factors described in the Patient Information Sheet and the ICF.

16 Nov 2012

The primary reason for this amendment was to revise the frequency of anti-JCV antibody testing in subjects who were anti-JCV antibody negative to align with the current safety recommendations for Tysabri.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results:
A Randomized, Blinded, Parallel-Group, Phase 2 Study Exploring the Safety, Tolerability, and Efficacy of Multiple Regimens of Natalizumab in Adult Subjects With Relapsing Multiple Sclerosis

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Clinical Trial Results: A Randomized, Blinded, Parallel-Group, Phase 2 Study Exploring the Safety, Tolerability, and Efficacy of Multiple Regimens of Natalizumab in Adult Subjects With Relapsing Multiple Sclerosis

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Primary: Cumulative Number of Combined Unique Active Lesions

Primary: Cumulative Number of Combined Unique Active Lesions

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Clinical Trial Results:
A Randomized, Blinded, Parallel-Group, Phase 2 Study Exploring the Safety, Tolerability, and Efficacy of Multiple Regimens of Natalizumab in Adult Subjects With Relapsing Multiple Sclerosis