Trial Outcomes & Findings for Extension Study to Evaluate Safety and Efficacy of Natalizumab in Japanese Participants With Relapsing-Remitting Multiple Sclerosis (NCT NCT01416155)

Last Updated: 2016-01-14

Results Overview

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 subject 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 subject or may have required intervention to prevent one of the other outcomes listed in the definition above.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

97 participants

Primary outcome timeframe

Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months

Results posted on

2016-01-14

Participant Flow

Subjects who participated in and completed all protocol-related evaluations through Week 24 in Study 101MS203 (NCT01440101) were eligible for this study.

Participant milestones

Participant milestones
Measure	Natalizumab 300 mg intravenous (IV) infusions of natalizumab open label every 4 weeks
Overall Study STARTED	97
Overall Study COMPLETED	39
Overall Study NOT COMPLETED	58

Reasons for withdrawal

Reasons for withdrawal
Measure	Natalizumab 300 mg intravenous (IV) infusions of natalizumab open label every 4 weeks
Overall Study Adverse Event	8
Overall Study Positive for anti-BG00002 antibodies	2
Overall Study Withdrawal by Subject	33
Overall Study Investigator decision	8
Overall Study Other	7

Baseline Characteristics

Extension Study to Evaluate Safety and Efficacy of Natalizumab in Japanese Participants With Relapsing-Remitting Multiple Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Natalizumab n=97 Participants 300 mg IV infusions of natalizumab open label every 4 weeks
Age, Continuous	37.2 years STANDARD_DEVIATION 8.67 • n=5 Participants
Age, Customized 18 to 19 years	1 participants n=5 Participants
Age, Customized 20 to 29 years	16 participants n=5 Participants
Age, Customized 30 to 39 years	44 participants n=5 Participants
Age, Customized 40 to 49 years	28 participants n=5 Participants
Age, Customized 50 to 59 years	7 participants n=5 Participants
Age, Customized >= 60 years	1 participants n=5 Participants
Sex: Female, Male Female	66 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months

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

Outcome measures

Outcome measures
Measure	Natalizumab n=97 Participants 300 mg IV infusions of natalizumab open label every 4 weeks
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Participants with an event related to study drug	33 participants
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Participants with an SAE related to study drug	7 participants
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Participants discontinuing treatment due to event	10 participants
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Participants withdrawing from study due to event	10 participants
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Participants with an event	92 participants
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Participants with a moderate or severe event	52 participants
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Participants with a severe event	10 participants
Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations Due to AEs Participants with an SAE	29 participants

PRIMARY outcome

Timeframe: Day 1 up to approximately 50 months

Population: Immunogenicity population: all participants who had received at least 1 infusion of BG00002, were negative for BG00002 antibodies at baseline and had at least 1 nonmissing post-baseline assessment of antibody status.

Negative is defined as negative for antibodies at all post-baseline results. Transient positivity is defined as only 1 positive result. Persistent positivity is defined as 2 positive results separated by at least 6 to 12 weeks.

Outcome measures

Outcome measures
Measure	Natalizumab n=96 Participants 300 mg IV infusions of natalizumab open label every 4 weeks
Number of Participants With Serum Antibodies to Natalizumab Participants negative	91 participants
Number of Participants With Serum Antibodies to Natalizumab Participants positive at any time	5 participants
Number of Participants With Serum Antibodies to Natalizumab Participants transiently positive	3 participants
Number of Participants With Serum Antibodies to Natalizumab Participants positive at final evaluation only	2 participants
Number of Participants With Serum Antibodies to Natalizumab Participants persistently positive	2 participants

SECONDARY outcome

Timeframe: Day 1 up to approximately 50 months

Clinical relapses are defined as new or recurrent neurologic symptoms, not associated with fever or infection, lasting for at least 24 hours, and accompanied by new objective neurological findings upon examination by the neurologist. The annualized relapse rate is calculated overall as the total number of relapses experienced in the study divided by the number of days followed in the study, and the ratio multiplied by 365. Obtained from a Poisson regression model, adjusted for the baseline relapse rate from study 101MS203 (NCT01440101).

Outcome measures

Outcome measures
Measure	Natalizumab n=26 Participants with a relapse 300 mg IV infusions of natalizumab open label every 4 weeks
Adjusted Annualized Relapse Rate	0.243 relapses per subject-years Interval 0.145 to 0.406

SECONDARY outcome

Timeframe: Day 1 up to Week 192

Population: n=number of participants with an assessment at given timepoint.

The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist.

Outcome measures

Outcome measures
Measure	Natalizumab n=97 Participants 300 mg IV infusions of natalizumab open label every 4 weeks
Mean Change From Baseline in the Assessment of Expanded Disability Status Scale (EDSS) up to Week 192 Change from Baseline to Week 24; n=86	-0.15 units on a scale Standard Deviation 0.490
Mean Change From Baseline in the Assessment of Expanded Disability Status Scale (EDSS) up to Week 192 Change from Baseline to Week 36; n=84	-0.08 units on a scale Standard Deviation 0.647
Mean Change From Baseline in the Assessment of Expanded Disability Status Scale (EDSS) up to Week 192 Change from Baseline to Week 48; n=78	-0.09 units on a scale Standard Deviation 0.585
Mean Change From Baseline in the Assessment of Expanded Disability Status Scale (EDSS) up to Week 192 Change from Baseline to Week 72; n=72	-0.04 units on a scale Standard Deviation 0.804
Mean Change From Baseline in the Assessment of Expanded Disability Status Scale (EDSS) up to Week 192 Change from Baseline to Week 84; n=60	-0.08 units on a scale Standard Deviation 0.764
Mean Change From Baseline in the Assessment of Expanded Disability Status Scale (EDSS) up to Week 192 Change from Baseline to Week 96; n=53	-0.10 units on a scale Standard Deviation 0.743
Mean Change From Baseline in the Assessment of Expanded Disability Status Scale (EDSS) up to Week 192 Change from Baseline to Week 108; n=46	-0.18 units on a scale Standard Deviation 0.791
Mean Change From Baseline in the Assessment of Expanded Disability Status Scale (EDSS) up to Week 192 Change from Baseline to Week 120; n=38	-0.12 units on a scale Standard Deviation 0.842
Mean Change From Baseline in the Assessment of Expanded Disability Status Scale (EDSS) up to Week 192 Change from Baseline to Week 132; n=31	-0.11 units on a scale Standard Deviation 0.854
Mean Change From Baseline in the Assessment of Expanded Disability Status Scale (EDSS) up to Week 192 Change from Baseline to Week 144; n=22	-0.07 units on a scale Standard Deviation 0.877
Mean Change From Baseline in the Assessment of Expanded Disability Status Scale (EDSS) up to Week 192 Change from Baseline to Week 156; n=11	0.14 units on a scale Standard Deviation 0.778
Mean Change From Baseline in the Assessment of Expanded Disability Status Scale (EDSS) up to Week 192 Change from Baseline to Week 168; n=8	0.31 units on a scale Standard Deviation 0.961
Mean Change From Baseline in the Assessment of Expanded Disability Status Scale (EDSS) up to Week 192 Change from Baseline to Week 180; n=8	0.25 units on a scale Standard Deviation 0.926
Mean Change From Baseline in the Assessment of Expanded Disability Status Scale (EDSS) up to Week 192 Change from Baseline to Week 192; n=2	0.50 units on a scale Standard Deviation 0.00
Mean Change From Baseline in the Assessment of Expanded Disability Status Scale (EDSS) up to Week 192 Change from Baseline to Final Treatment Visit;n=36	-0.17 units on a scale Standard Deviation 0.862
Mean Change From Baseline in the Assessment of Expanded Disability Status Scale (EDSS) up to Week 192 Change from Baseline to Week 12; n=92	-0.05 units on a scale Standard Deviation 0.486
Mean Change From Baseline in the Assessment of Expanded Disability Status Scale (EDSS) up to Week 192 Change from Baseline to Week 60; n=76	-0.09 units on a scale Standard Deviation 0.534

Adverse Events

Natalizumab

Serious events: 29 serious events

Other events: 78 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Natalizumab n=97 participants at risk 300 mg IV infusions of natalizumab open label every 4 weeks
Blood and lymphatic system disorders Eosinophilia	1.0% 1/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Endocrine disorders Hypothyroidism	1.0% 1/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Gastrointestinal disorders Enteritis	1.0% 1/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Gastrointestinal disorders Haemorrhoids	1.0% 1/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Gastrointestinal disorders Inguinal hernia	1.0% 1/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Gastrointestinal disorders Oesophageal ulcer	1.0% 1/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Infections and infestations Bronchitis	1.0% 1/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Infections and infestations Meningitis	2.1% 2/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Infections and infestations Mycoplasma infection	1.0% 1/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Metabolism and nutrition disorders Decreased appetite	1.0% 1/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Musculoskeletal and connective tissue disorders Arthralgia	1.0% 1/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine cancer	1.0% 1/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Nervous system disorders Central nervous system lesion	1.0% 1/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Nervous system disorders Multiple sclerosis relapse	17.5% 17/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Nervous system disorders Trigeminal neuralgia	1.0% 1/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Pregnancy, puerperium and perinatal conditions Ectopic pregnancy	1.0% 1/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Psychiatric disorders Asperger's disorder	1.0% 1/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Psychiatric disorders Schizophrenia	1.0% 1/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Reproductive system and breast disorders Uterine prolapse	1.0% 1/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	1.0% 1/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Skin and subcutaneous tissue disorders Rash	1.0% 1/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.

Other adverse events

Other adverse events
Measure	Natalizumab n=97 participants at risk 300 mg IV infusions of natalizumab open label every 4 weeks
Gastrointestinal disorders Constipation	7.2% 7/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Gastrointestinal disorders Dental caries	6.2% 6/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Gastrointestinal disorders Diarrhoea	8.2% 8/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Gastrointestinal disorders Gastritis	5.2% 5/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Gastrointestinal disorders Stomatitis	5.2% 5/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
General disorders Pyrexia	6.2% 6/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Immune system disorders Seasonal allergy	6.2% 6/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Infections and infestations Cystitis	5.2% 5/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Infections and infestations Gastroenteritis	5.2% 5/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Infections and infestations Influenza	12.4% 12/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Infections and infestations Nasopharyngitis	50.5% 49/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Infections and infestations Pharyngitis	8.2% 8/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Injury, poisoning and procedural complications Fall	5.2% 5/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Nervous system disorders Dizziness	5.2% 5/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Nervous system disorders Headache	6.2% 6/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Nervous system disorders Multiple sclerosis relapse	21.6% 21/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Psychiatric disorders Depression	5.2% 5/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Psychiatric disorders Insomnia	10.3% 10/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Skin and subcutaneous tissue disorders Eczema	8.2% 8/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
Skin and subcutaneous tissue disorders Rash	8.2% 8/97 • Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.

Additional Information

Biogen Study Medical Director

Biogen

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
Publication restrictions are in place

Restriction type: OTHER