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The primary objective of the study is to further evaluate the long-term safety and tolerability profiles of BG00002 (natalizumab) in Japanese participants with relapsing-remitting multiple sclerosis (RRMS). The secondary objective of this study is to further evaluate the long-term efficacy profile of BG00002 in Japanese participants with RRMS.
This is a multicenter, long-term, open-label, extension study in participants who have successfully completed Study 101MS203 (NCT01440101).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| natalizumab | Experimental | 300 mg intravenous (IV) infusions of natalizumab every 4 weeks until product is approved in Japan or development is discontinued in Japan, whichever comes first. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| natalizumab | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events (AEs), Serious AEs (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 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. | Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months |
| Number of Participants With Serum Antibodies to Natalizumab | 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. | Day 1 up to approximately 50 months |
| Measure | Description | Time Frame |
|---|---|---|
| Adjusted Annualized Relapse Rate | 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). |
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Key Inclusion Criteria:
Key Exclusion Criteria Medical History
Treatment History
Miscellaneous
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Biogen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Chiba | Chiba | 260-8677 | Japan | ||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27921221 | Derived | Saida T, Kira JI, Kishida S, Yamamura T, Ohtsuka N, Ling Y, Torii S, Lucas N, Kuesters G, Steiner D, Tibung JT; Natalizumab Trial Principal Investigators. Safety and Efficacy of Natalizumab in Japanese Patients with Relapsing-Remitting Multiple Sclerosis: Open-Label Extension Study of a Phase 2 Trial. Neurol Ther. 2017 Jun;6(1):39-55. doi: 10.1007/s40120-016-0059-z. Epub 2016 Dec 5. |
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Subjects who participated in and completed all protocol-related evaluations through Week 24 in Study 101MS203 (NCT01440101) were eligible for this study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Natalizumab | 300 mg intravenous (IV) infusions of natalizumab open label every 4 weeks |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Day 1 up to approximately 50 months |
| Mean Change From Baseline in the Assessment of Expanded Disability Status Scale (EDSS) up to Week 192 | 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. | Day 1 up to Week 192 |
| Fukuoka |
| Fukuoka |
| 812-8582 |
| Japan |
| Research Site | Hiroshima | Hiroshima | 734-8551 | Japan |
| Research Site | Sapporo | Hokkaido | 060-8648 | Japan |
| Research Site | Sapporo | Hokkaido | 063-0005 | Japan |
| Research Site | Tsukuba | Ibaraki | 305-8576 | Japan |
| Research Site | Morioka | Iwate | 020-8505 | Japan |
| Research Site | Yokohama | Kanagawa | 232-0024 | Japan |
| Research Site | Kyoto | Kyoto | 604-8453 | Japan |
| Research Site | Kyoto | Kyoto | 606-8507 | Japan |
| Research Site | Kyoto | Kyoto | 616-8255 | Japan |
| Research Site | Sendai | Miyagi | 980-8574 | Japan |
| Research Site | Niigata | Niigata | 951-8520 | Japan |
| Research Site | Osaka | Osaka | 556-0016 | Japan |
| Research Site | Suita | Osaka | 565-0871 | Japan |
| Research Site | Kawagoe | Saitama | 350-8550 | Japan |
| Research Site | Tokorozawa | Saitama | 359-8513 | Japan |
| Research Site | Bunkyo-ku | Tokyo | 113-8431 | Japan |
| Research Site | Bunkyo-ku | Tokyo | 113-8519 | Japan |
| Research Site | Kodaira | Tokyo | 187-8551 | Japan |
| Research Site | Ōta-ku | Tokyo | 145-0065 | Japan |
| Research Site | Ube | Yamaguchi | 755-8505 | Japan |
| COMPLETED |
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| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Natalizumab | 300 mg IV infusions of natalizumab open label every 4 weeks |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| ||||||||||||||||||||||
| Age, Customized | Number | participants |
| |||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| 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 Adverse Events (AEs), Serious AEs (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 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. | Safety population: all participants who received at least 1 dose of study treatment. | Posted | Number | participants | Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months |
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| ||||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With Serum Antibodies to Natalizumab | 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. | 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. | Posted | Number | participants | Day 1 up to approximately 50 months |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Adjusted Annualized Relapse Rate | 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). | Posted | Number | 95% Confidence Interval | relapses per subject-years | Day 1 up to approximately 50 months | Participants with a relapse | Participants |
|
| |||||||||||||||||||||||||||||||||||
| Secondary | Mean Change From Baseline in the Assessment of Expanded Disability Status Scale (EDSS) up to Week 192 | 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. | n=number of participants with an assessment at given timepoint. | Posted | Mean | Standard Deviation | units on a scale | Day 1 up to Week 192 |
|
|
Day 1 through First Follow-Up (12 Weeks After Last Infusion) +/- 7 days. Approximately 62 months.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Natalizumab | 300 mg IV infusions of natalizumab open label every 4 weeks | 29 | 97 | 78 | 97 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Eosinophilia | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Enteritis | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Inguinal hernia | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Oesophageal ulcer | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Meningitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Mycoplasma infection | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Uterine cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 13.1 | Systematic Assessment |
| |
| Central nervous system lesion | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Multiple sclerosis relapse | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Trigeminal neuralgia | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Ectopic pregnancy | Pregnancy, puerperium and perinatal conditions | MedDRA 13.1 | Systematic Assessment |
| |
| Asperger's disorder | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
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| Schizophrenia | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Uterine prolapse | Reproductive system and breast disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Dental caries | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Seasonal allergy | Immune system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
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| Pharyngitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA 13.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
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| Multiple sclerosis relapse | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
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| Eczema | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Biogen Study Medical Director | Biogen | clinicaltrials@biogen.com |
| ID | Term |
|---|---|
| D020529 | Multiple Sclerosis, Relapsing-Remitting |
| D009103 | Multiple Sclerosis |
| 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 |
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| ID | Term |
|---|---|
| D000069442 | Natalizumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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| 30 to 39 years |
|
| 40 to 49 years |
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| 50 to 59 years |
|
| >= 60 years |
|
| Title | Measurements |
|---|---|
|
| Participants with an event related to study drug |
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| Participants with an SAE |
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| Participants with an SAE related to study drug |
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| Participants discontinuing treatment due to event |
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| Participants withdrawing from study due to event |
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| Participants with a relapse |
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