Multiple SclerosisPhase 2/3Tysabri JapanNCT01440101
Natalizumab (BG00002, Tysabri) Study in Japanese Participants With Relapsing-Remitting Multiple Sclerosis (RRMS)
A Phase 2/3 study testing Natalizumab (BG00002) in people with Multiple Sclerosis, run by Biogen at 17 sites in Japan.
Trial summary
The primary objective of Part A is to determine the safety and tolerability of natalizumab administered over 24 weeks in Japanese participants with relapsing-remitting multiple sclerosis (MS). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Natalizumab (BG00002)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 106 participants
- Where
- 17 sitesJapan
- Study dates
- Nov 2010to Aug 2012
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must give written informed consent and any authorizations required by local law.
- Must have a diagnosis of relapsing-remitting MS, as defined by the revised McDonald criteria 1 through 4 (Polman et al, 2005). All other possible neurologic diagnoses must have been reasonably excluded by means of laboratory and/or imaging studies, in the opinion of the Investigator.
- Japanese men and women aged 18 to 65, inclusive, at the time of informed consent.
- All male subjects and female subjects of childbearing potential must practice effective contraception during the study and be able to continue contraception for 12 weeks after their last dose of study treatment.
- Must have an Expanded Disability Status Scale (EDSS) score between 0.0 and 6.0, inclusive.
- Must have experienced at least 1 medically documented clinical exacerbation within 12 months of enrollment.
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- Must be willing to remain free from concomitant immunosuppressive or immunomodulatory treatment (including interferon beta [IFNβ] and chronic systemic corticosteroids) for the duration of the study.
- Must have a baseline MRI, conducted within 35 calendar days prior to enrollment.
- Must give written informed consent and any authorizations required by local law.
- Must have a diagnosis of relapsing-remitting MS, as defined by the revised McDonald criteria 1 through 4 (Polman et al, 2005). All other possible neurologic diagnoses must have been reasonably excluded by means of laboratory and/or imaging studies, in the opinion of the Investigator.
- Japanese men and women aged 18 to 65, inclusive, at the time of informed consent.
- All male subjects and female subjects of childbearing potential must practice effective contraception during the study and be able to continue contraception for 12 weeks after their last dose of study treatment.
- Must have an EDSS score between 0.0 and 5.5, inclusive.
- Must have experienced at least 1 medically documented clinical exacerbation within 12 months of enrollment.
- Must be willing to remain free from concomitant immunosuppressive or immunomodulatory treatment (including IFNβ and chronic systemic corticosteroids) for the duration of the study.
- Prior to enrollment all subjects must have: a screening MRI, or documentation of an MRI within the subject's medical record within 1 year of the screening visit, which reveals 3 or more T2 hyperintense lesions consistent with MS, and a baseline MRI, conducted within 7 calendar days prior to enrollment, which reveals at least 1 MRI lesion consistent with MS.
Who cannot join
- Diagnosis or history of neuromyelitis optica (NMO), e.g., a long spinal lesion extending over 3 or more vertebral bodies was detected, or the subject has a history of positive tests for anti-aquaporin-4 (anti-AQP4) antibodies.
- The subject is considered by the Investigator to be immunocompromised, based on medical history, physical examination, laboratory testing, or prior immunosuppressive or immunomodulating treatment.
- An MS exacerbation (relapse) within 30 days prior to enrollment or, in the opinion of the Investigator, the subject has not stabilized from a relapse prior to enrollment at Week 0.
- History of malignancy.
- Known history of, or positive test result for human immunodeficiency virus (HIV) infection.
- Known history of or positive test result for hepatitis C virus or hepatitis B virus within the year prior to enrollment.
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- History of severe allergic or anaphylactic reactions or known drug hypersensitivity.
- A clinically significant infectious illness within 30 days prior to enrollment.
- Abnormal liver function test results at screening: alanine aminotransferase (ALT), or aspartate aminotransferase (AST) >2 times of the upper limit of normal (ULN) or bilirubin >1.5 times of the ULN during screening.
- Previous treatment with natalizumab, any murine protein, or any other therapeutic monoclonal antibody.
- Any prior treatment with any of the following medications: total lymphoid irradiation, cladribine, T-cell or T-cell receptor vaccination.
- Treatment with immunosuppressant medications, e.g., azathioprine, cyclophosphamide, methotrexate, and fingolimod within 6 months prior to enrollment, or mitoxantrone and cyclosporine within 12 months prior to enrollment.
- Treatment with any of the following medications or procedures within 6 months prior to enrollment: intravenous immunoglobulin (IVIg), plasmapheresis, or cytapheresis.
- Treatment with immunomodulatory medications (including IFNβ and glatiramer acetate [GA]) within 2 weeks of enrollment.
- Treatment with any of the following medications within 30 days of enrollment: intravenous corticosteroid treatment, systemic corticosteroid treatment, 4-aminopyridine or related products.
- Participation in any other investigational treatment within the 6 months prior to enrollment or concurrent with this study.
- Part B
- Diagnosis or history of NMO, e.g., a long spinal lesion extending over 3 or more vertebral bodies was detected, or the subject has a history of positive tests for anti-AQP4 antibodies.
- The subject is considered by the Investigator to be immunocompromised, based on medical history, physical examination, laboratory testing, or prior immunosuppressive or immunomodulating treatment.
- An MS exacerbation (relapse) within 30 days prior to enrollment or, in the opinion of the Investigator, the subject has not stabilized from a relapse prior to enrollment at Week 0.
- History of malignancy.
- Known history, or positive test result of HIV infection.
- Known history of or positive test result for hepatitis C virus or hepatitis B virus within the year prior to Enrollment.
- History of severe allergic or anaphylactic reactions or known drug hypersensitivity.
- A clinically significant infectious illness within 30 days prior to Enrollment.
- Abnormal liver function test results at screening: ALT or AST >2 times of the ULN or bilirubin >1.5 times of the ULN during screening.
- Previous treatment with natalizumab, any murine protein, or any other therapeutic monoclonal antibody.
- Any prior treatment with any of the following medications: total lymphoid irradiation, cladribine, T-cell or T-cell receptor vaccination.
- Treatment with immunosuppressant medications, e.g., azathioprine, cyclophosphamide, methotrexate, and fingolimod within 6 months prior to enrollment, or mitoxantrone and cyclosporine within 12 months prior to enrollment.
- Treatment with any of the following medications or procedures within 6 months prior to enrollment: IVIg, plasmapheresis, or cytapheresis.
- Treatment with immunomodulatory medications (including IFNβ and GA) within 2 weeks of enrollment.
- Treatment with any of the following medications within 30 days of enrollment: intravenous corticosteroid treatment, systemic corticosteroid treatment, 4-aminopyridine or related products.
- Participation in any other investigational treatment within the 6 months prior to enrollment or concurrent with this study.
- NOTE: Other protocol defined inclusion/exclusion criteria may apply.
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
Japan17 sites
Research Site
Chiba
Research Site
Fukuoka
Research Site
Hiroshima
Research Site
Kawagoe
Research Site
Kyoto
Research Site
Morioka
Research Site
Niigata
Research Site
Osaka
Research Site
Otaku
Research Site
Sapporo
Research Site
Sendai
Research Site
Suita
Research Site
Tokorozawa
Research Site
Tokyo
Research Site
Tsukuba
Research Site
Ube
Research Site
Yokohama
About this study
Official title: Multicenter Study of BG00002 in Japanese Subjects With RRMS, Consisting of a Multiple-Dose, Open-Label Evaluation of Its Safety, Tolerability, Pharmacokinetics and Pharmacodynamics (Part A) and a Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose Evaluation of Safety and Efficacy (Part B)
The primary objective of Part A is to determine the safety and tolerability of natalizumab administered over 24 weeks in Japanese participants with relapsing-remitting multiple sclerosis (MS). The endpoints for this will include assessment of adverse evetns (AEs), changes in laboratory evaluations, vital signs, Expanded Disability Status Scale (EDSS) scores, and changes in physical and neurological examination findings. The secondary objectives of Part A are to characterize the pharmacokinetics (PK) profile and pharmacodynamics (PD) of natalizumab.
The primary objective of Part B is to determine if natalizumab, when compared to placebo, is effective in treating Japanese participants with relapsing-remitting MS, as measured by new active lesions on cranial magnetic resonance imaging (MRI) scans over 24 weeks. New active lesions are the sum of the gadolinium-enhancing (Gd+) lesions and any new or newly-enlarging T2-hyperintense lesions that do not enhance. The primary endpoint is the rate of development of new active lesions over 24 weeks.
Secondary objectives of Part B are to determine over 24 weeks whether natalizumab, when compared to placebo, is effective in reducing the frequency of clinical exacerbations, reducing the number of Gd+ lesions, reducing the number of new or newly-enlarging T2-hyperintense lesions on brain MRI scans, increasing the proportion of relapse-free participants, and improving outcomes on visual analog scale (VAS) assessing the participant's global impression of his/her well-being. Additional objectives are to assess the safety and tolerability, the incidence of serum antibodies to natalizumab and the PK profile of natalizumab.
Read the detailed description
This multicenter study has 2 parts and is designed to provide data in Japanese participants, as required for registration of natalizumab (BG00002) in Japan. Part A will consist of an open-label cohort of 12 participants who will receive 300 mg natalizumab intravenously (IV) every 4 weeks over a 6-month treatment period. Part B will consist of a double-blind, placebo-controlled cohort of approximately 90 participants randomized in a ratio of 1:1 to receive IV infusions of placebo or 300 mg BG00002 every 4 weeks over a 6-month period.
- Conditions
- Multiple Sclerosis
- Being tested
- Natalizumab (BG00002), Placebo
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Natalizumab (BG00002)Drug
Also called Tysabri
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Double-blind Natalizumab 300 mg | Experimental | 300 mg IV infusions of natalizumab over 60 minutes every 4 weeks for 20 weeks Receives: Drug: Natalizumab (BG00002) |
| Double-blind Placebo | Placebo comparator | IV infusions of placebo over 60 minutes every 4 weeks for 20 weeks Receives: Drug: Placebo |
| Open-label Natalizumab | Experimental | 300 mg IV infusions of natalizumab over 60 minutes every 4 weeks for 20 weeks Receives: Drug: Natalizumab (BG00002) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: Number of Participants With Adverse Events (AEs)
AE=any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. Serious AE (SAE)=any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigator, was a life threatening event; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; or any other medically important event that, in the opinion of the Investigator, may have jeopardized the participant or may have required intervention to prevent one of the other outcomes listed in the definition above. Events were categorized as related or not related; severity was categorized as mild, moderate, or severe.
Measured: Baseline (Week 0) to Week 24
Part B: Rate of Development of New Active Lesions Over 24 Weeks
New active lesions were the sum of the gadolinium-enhancing (Gd+) lesions and any new or newly enlarging T2 hyperintense lesions that did not enhance as seen on cranial magnetic resonance imaging (MRI) scans. The rate is calculated for each participant as the ordinary least squares slope of the cumulative new active lesions over time.
Measured: Baseline (Week 0) to Week 24
Secondary outcomes (17)
Part B: Cumulative Number of New Active Lesions Over 24 Weeks
Measured: Baseline (Week 0) to Week 24
Part B: Adjusted Annualized Relapse Rate Over 24 Weeks
The frequency of clinical exacerbations over 24 weeks was assessed using an annualized relapse rate that was calculated for each treatment group as the total number of relapses experienced in the group over the 24 weeks of treatment, divided by the total number of subject-years followed in the study. Obtained from a Poisson regression model, adjusted for the baseline relapse rate.
Measured: Week 24
Part B: Cumulative Number of Gd+ Lesions Over 24 Weeks
Measured: Baseline (Week 0) to Week 24
Part B: Cumulative Number Of New Or Newly Enlarging, Non-Enhancing T2-Hyperintense Lesions Over 24 Weeks
Measured: Baseline (Week 0) to Week 24
Part B: Number of Participants Who Were Relapse Free Over 24 Weeks
Participants were categorized as relapse free=yes, relapse free=no, or relapse free=unknown. The category of relapse free=unknown includes participants who withdrew from the study and did not experience a relapse prior to withdrawal.
Measured: Baseline (Week 0) to Week 24
Part B: Change From Baseline to Weeks 12 and 24 in the Global Assessment of Well-Being As Assessed by Participants Using a Visual Analog Scale (VAS)
The participant's self-rating of global impression of his/her well-being was assessed with a VAS. The instrument ranged from 0 to 100 (mm), where a score of 0 denoted 'poor' and a score of 100 denoted 'excellent.'
Measured: Baseline (Week 0), Week 12, Week 24
Part A: Concentration of Natalizumab in Serum
The concentration of BG00002 in serum was determined using an Enzyme Linked Immunosorbent Assay (ELISA).
Measured: Week 0: pre-dose, post-dose and 2, 24, 48 and 96 hours post-dose; 7, 14, and 21 days post-dose; Weeks 4, 8, 12, and 16: pre-dose; Week 20 pre-dose, post-dose, and 2, 24, 48 and 96 hours post-dose; 7, 14, 21, and 28 days post-dose
Part B: Concentration of Natalizumab in Serum
The concentration of BG00002 in serum was determined using an Enzyme Linked Immunosorbent Assay (ELISA).
Measured: Baseline (Week 0), Week 12, Week 24
Part A: Pharmacokinetic (PK) Profile of Natalizumab in Serum: Cmax
Observed maximum concentration (Cmax) was calculated using non-compartmental methods.
Measured: Dose 1/Week 0: pre-dose, post-dose and 4, 24, 48 and 96 hours post-dose; Dose 6/Week 20 pre-dose, post-dose, and 4, 24, 48 and 96 hours post-dose; 7, 14, and 21 days post-dose
Part A: Pharmacokinetic (PK) Profile of Natalizumab in Serum: AUC(0-last) and (0-AUC∞)
Area under the curve to the last measurable concentration (AUC[0-last]); and area under the curve extrapolated to infinity (0-AUC∞) were calculated using non-compartmental methods.
Measured: Dose 1/Week 0: pre-dose, post-dose and 4, 24, 48 and 96 hours post-dose; Dose 6/Week 20 pre-dose, post-dose, and 4, 24, 48 and 96 hours post-dose; 7, 14, and 21 days post-dose
Part A: Pharmacokinetic (PK) Profile of Natalizumab in Serum: Tmax and T1/2
Time to maximum concentration (Tmax) and half-life (T1/2) were calculated using non-compartmental methods.
Measured: Dose 1/Week 0: pre-dose, post-dose and 4, 24, 48 and 96 hours post-dose; Dose 6/Week 20 pre-dose, post-dose, and 4, 24, 48 and 96 hours post-dose; 7, 14, and 21 days post-dose
Part A: Pharmacokinetic (PK) Profile of Natalizumab in Serum: Vd
Volume of distribution (Vd) was calculated using non-compartmental methods.
Measured: Dose 1/Week 0: pre-dose, post-dose and 4, 24, 48 and 96 hours post-dose; Dose 6/Week 20 pre-dose, post-dose, and 4, 24, 48 and 96 hours post-dose; 7, 14, and 21 days post-dose
Part A: Pharmacokinetic (PK) Profile of Natalizumab in Serum: CL
Systemic clearance (CL) was calculated using non-compartmental methods.
Measured: Dose 1/Week 0: pre-dose, post-dose and 4, 24, 48 and 96 hours post-dose
Part B: Status of Serum Antibodies to Natalizumab
Persistent positivity is defined as 2 positive results separated by at least 6 to 12 weeks.
Measured: Baseline (Week 0) and Week 24
Part B: Number of Participants With Adverse Events (AEs)
AE=any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. Serious AE (SAE)=any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigator, was a life threatening event; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; or any other medically important event that, in the opinion of the Investigator, may have jeopardized the participant or may have required intervention to prevent one of the other outcomes listed in the definition above. Events were categorized as related or not related; severity was categorized as mild, moderate, or severe.
Measured: Baseline (Week 0) to Week 24
Part A: Natalizumab Binding Saturation Of α4 Integrin Sites On Peripheral Blood Mononuclear Cells (PBMC)
Pharmacodynamic activity was assessed by measuring the degree of saturation by BG00002 of the very late antigen-4 (VLA-4, also known as α4β1 integrin) receptor on peripheral blood mononuclear cell populations. This was accomplished by staining cells with phycoerythrin-conjugated anti-human immunoglobulin G4 (IgG4) antibody (hIgG4-PE) to label the cell-bound BG00002, followed by flow cytometric detection and quantification.
Measured: Pre-dose; 4 hours post-dose; 7, 14, 21, and 28 days post-dose; Weeks 8, 12, and 16: pre-dose; Week 20: pre-dose; 4 hours post-dose; 7, 14, 21, and 28 days post-dose
Part A: Summary of Lymphocyte Counts Over Time
Measured: Baseline [Week 0]); 28 days post-dose; Weeks 12, 24, and 32 (follow-up)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2011 (estimated)
- Study startNov 2010
- Primary completionAug 2012
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by BiogenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Biogen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01440101
- Sponsor's protocol ID
- 101MS203
- Acronym
- Tysabri Japan
- Status last verified
- Oct 2014
- First submitted
- 14 Apr 2011
- Last updated
- 21 Oct 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Saida T, Kira JI, Kishida S, Yamamura T, Sudo Y, Ogiwara K, Tibung JT, Lucas N, Subramanyam M; Natalizumab Trial Principal Investigators. Efficacy, safety, and pharmacokinetics of natalizumab in Japanese multiple sclerosis patients: A double-blind, randomized controlled trial and open-label pharmacokinetic study. Mult Scler Relat Disord. 2017 Jan;11:25-31. doi: 10.1016/j.msard.2016.11.002. Epub 2016 Nov 11.
PubMed 28104251Saida T, Kira JI, Kishida S, Yamamura T, Ohtsuka N, Dong Q, Tibung JT. Natalizumab for Achieving Relapse-Free, T1 Gadolinium-Enhancing-Lesion-Free, and T2 Lesion-Free Status in Japanese Multiple Sclerosis Patients: A Phase 2 Trial Subanalysis. Neurol Ther. 2017 Jun;6(1):153-159. doi: 10.1007/s40120-016-0062-4. Epub 2017 Jan 11.
PubMed 28078634
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Study of BG00002 in Japanese Subjects With RRMS, Consisting of a Multiple-Dose, Open-Label Evaluation of Its Safety, Tolerability, Pharmacokinetics and Pharmacodynamics (Part A) and a Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose Evaluation of Safety and Efficacy (Part B)
- ClinicalTrials.gov ID
- NCT01440101
- Acronym / sponsor ID
- Tysabri Japan / 101MS203
- Conditions
- Multiple Sclerosis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Study start
- Nov 2010
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 26 Sep 2011 (estimated)
- Results
- Posted 21 Oct 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of Part A is to determine the safety and tolerability of natalizumab administered over 24 weeks in Japanese participants with relapsing-remitting multiple sclerosis (MS). The endpoints for this will include assessment of adverse evetns (AEs), changes in laboratory evaluations, vital signs, Expanded Disability Status Scale (EDSS) scores, and changes in physical and neurological examination findings. The secondary objectives of Part A are to characterize the pharmacokinetics (PK) profile and pharmacodynamics (PD) of natalizumab.
The primary objective of Part B is to determine if natalizumab, when compared to placebo, is effective in treating Japanese participants with relapsing-remitting MS, as measured by new active lesions on cranial magnetic resonance imaging (MRI) scans over 24 weeks. New active lesions are the sum of the gadolinium-enhancing (Gd+) lesions and any new or newly-enlarging T2-hyperintense lesions that do not enhance. The primary endpoint is the rate of development of new active lesions over 24 weeks.
Secondary objectives of Part B are to determine over 24 weeks whether natalizumab, when compared to placebo, is effective in reducing the frequency of clinical exacerbations, reducing the number of Gd+ lesions, reducing the number of new or newly-enlarging T2-hyperintense lesions on brain MRI scans, increasing the proportion of relapse-free participants, and improving outcomes on visual analog scale (VAS) assessing the participant's global impression of his/her well-being. Additional objectives are to assess the safety and tolerability, the incidence of serum antibodies to natalizumab and the PK profile of natalizumab.
Detailed description
This multicenter study has 2 parts and is designed to provide data in Japanese participants, as required for registration of natalizumab (BG00002) in Japan. Part A will consist of an open-label cohort of 12 participants who will receive 300 mg natalizumab intravenously (IV) every 4 weeks over a 6-month treatment period. Part B will consist of a double-blind, placebo-controlled cohort of approximately 90 participants randomized in a ratio of 1:1 to receive IV infusions of placebo or 300 mg BG00002 every 4 weeks over a 6-month period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Double-blind Natalizumab 300 mg | Experimental | Drug: Natalizumab (BG00002)300 mg IV infusions of natalizumab over 60 minutes every 4 weeks for 20 weeks |
| Double-blind Placebo | Placebo comparator | Drug: PlaceboIV infusions of placebo over 60 minutes every 4 weeks for 20 weeks |
| Open-label Natalizumab | Experimental | Drug: Natalizumab (BG00002)300 mg IV infusions of natalizumab over 60 minutes every 4 weeks for 20 weeks |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Must give written informed consent and any authorizations required by local law.
- Must have a diagnosis of relapsing-remitting MS, as defined by the revised McDonald criteria 1 through 4 (Polman et al, 2005). All other possible neurologic diagnoses must have been reasonably excluded by means of laboratory and/or imaging studies, in the opinion of the Investigator.
- Japanese men and women aged 18 to 65, inclusive, at the time of informed consent.
- All male subjects and female subjects of childbearing potential must practice effective contraception during the study and be able to continue contraception for 12 weeks after their last dose of study treatment.
- Must have an Expanded Disability Status Scale (EDSS) score between 0.0 and 6.0, inclusive.
Key exclusion criteria (34 listed)
- Diagnosis or history of neuromyelitis optica (NMO), e.g., a long spinal lesion extending over 3 or more vertebral bodies was detected, or the subject has a history of positive tests for anti-aquaporin-4 (anti-AQP4) antibodies.
- The subject is considered by the Investigator to be immunocompromised, based on medical history, physical examination, laboratory testing, or prior immunosuppressive or immunomodulating treatment.
- An MS exacerbation (relapse) within 30 days prior to enrollment or, in the opinion of the Investigator, the subject has not stabilized from a relapse prior to enrollment at Week 0.
- History of malignancy.
- Known history of, or positive test result for human immunodeficiency virus (HIV) infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Natalizumab (BG00002)Also: Tysabri | Drug | Double-blind Natalizumab 300 mg, Open-label Natalizumab |
| Placebo | Drug | Double-blind Placebo |
Primary outcome
Part A: Number of Participants With Adverse Events (AEs)
Time frame: Baseline (Week 0) to Week 24
AE=any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. Serious AE (SAE)=any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigator, was a life threatening event; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; or any other medically important event that, in the opinion of the Investigator, may have jeopardized the participant or may have required intervention to prevent one of the other outcomes listed in the definition above. Events were categorized as related or not related; severity was categorized as mild, moderate, or severe.
Part B: Rate of Development of New Active Lesions Over 24 Weeks
Time frame: Baseline (Week 0) to Week 24
New active lesions were the sum of the gadolinium-enhancing (Gd+) lesions and any new or newly enlarging T2 hyperintense lesions that did not enhance as seen on cranial magnetic resonance imaging (MRI) scans. The rate is calculated for each participant as the ordinary least squares slope of the cumulative new active lesions over time.
17 secondary outcomes
Part B: Cumulative Number of New Active Lesions Over 24 Weeks
Time frame: Baseline (Week 0) to Week 24
Part B: Adjusted Annualized Relapse Rate Over 24 Weeks
Time frame: Week 24
Part B: Cumulative Number of Gd+ Lesions Over 24 Weeks
Time frame: Baseline (Week 0) to Week 24
Part B: Cumulative Number Of New Or Newly Enlarging, Non-Enhancing T2-Hyperintense Lesions Over 24 Weeks
Time frame: Baseline (Week 0) to Week 24
Part B: Number of Participants Who Were Relapse Free Over 24 Weeks
Time frame: Baseline (Week 0) to Week 24
Part B: Change From Baseline to Weeks 12 and 24 in the Global Assessment of Well-Being As Assessed by Participants Using a Visual Analog Scale (VAS)
Time frame: Baseline (Week 0), Week 12, Week 24
Part A: Concentration of Natalizumab in Serum
Time frame: Week 0: pre-dose, post-dose and 2, 24, 48 and 96 hours post-dose; 7, 14, and 21 days post-dose; Weeks 4, 8, 12, and 16: pre-dose; Week 20 pre-dose, post-dose, and 2, 24, 48 and 96 hours post-dose; 7, 14, 21, and 28 days post-dose
Part B: Concentration of Natalizumab in Serum
Time frame: Baseline (Week 0), Week 12, Week 24
Part A: Pharmacokinetic (PK) Profile of Natalizumab in Serum: Cmax
Time frame: Dose 1/Week 0: pre-dose, post-dose and 4, 24, 48 and 96 hours post-dose; Dose 6/Week 20 pre-dose, post-dose, and 4, 24, 48 and 96 hours post-dose; 7, 14, and 21 days post-dose
Part A: Pharmacokinetic (PK) Profile of Natalizumab in Serum: AUC(0-last) and (0-AUC∞)
Time frame: Dose 1/Week 0: pre-dose, post-dose and 4, 24, 48 and 96 hours post-dose; Dose 6/Week 20 pre-dose, post-dose, and 4, 24, 48 and 96 hours post-dose; 7, 14, and 21 days post-dose
Part A: Pharmacokinetic (PK) Profile of Natalizumab in Serum: Tmax and T1/2
Time frame: Dose 1/Week 0: pre-dose, post-dose and 4, 24, 48 and 96 hours post-dose; Dose 6/Week 20 pre-dose, post-dose, and 4, 24, 48 and 96 hours post-dose; 7, 14, and 21 days post-dose
Part A: Pharmacokinetic (PK) Profile of Natalizumab in Serum: Vd
Time frame: Dose 1/Week 0: pre-dose, post-dose and 4, 24, 48 and 96 hours post-dose; Dose 6/Week 20 pre-dose, post-dose, and 4, 24, 48 and 96 hours post-dose; 7, 14, and 21 days post-dose
Part A: Pharmacokinetic (PK) Profile of Natalizumab in Serum: CL
Time frame: Dose 1/Week 0: pre-dose, post-dose and 4, 24, 48 and 96 hours post-dose
Part B: Status of Serum Antibodies to Natalizumab
Time frame: Baseline (Week 0) and Week 24
Part B: Number of Participants With Adverse Events (AEs)
Time frame: Baseline (Week 0) to Week 24
Part A: Natalizumab Binding Saturation Of α4 Integrin Sites On Peripheral Blood Mononuclear Cells (PBMC)
Time frame: Pre-dose; 4 hours post-dose; 7, 14, 21, and 28 days post-dose; Weeks 8, 12, and 16: pre-dose; Week 20: pre-dose; 4 hours post-dose; 7, 14, 21, and 28 days post-dose
Part A: Summary of Lymphocyte Counts Over Time
Time frame: Baseline [Week 0]); 28 days post-dose; Weeks 12, 24, and 32 (follow-up)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28104251Saida T, Kira JI, Kishida S, Yamamura T, Sudo Y, Ogiwara K, Tibung JT, Lucas N, Subramanyam M; Natalizumab Trial Principal Investigators. Efficacy, safety, and pharmacokinetics of natalizumab in Japanese multiple sclerosis patients: A double-blind, randomized controlled trial and open-label pharmacokinetic study. Mult Scler Relat Disord. 2017 Jan;11:25-31. doi: 10.1016/j.msard.2016.11.002. Epub 2016 Nov 11.
- Derived from this study: PubMed 28078634Saida T, Kira JI, Kishida S, Yamamura T, Ohtsuka N, Dong Q, Tibung JT. Natalizumab for Achieving Relapse-Free, T1 Gadolinium-Enhancing-Lesion-Free, and T2 Lesion-Free Status in Japanese Multiple Sclerosis Patients: A Phase 2 Trial Subanalysis. Neurol Ther. 2017 Jun;6(1):153-159. doi: 10.1007/s40120-016-0062-4. Epub 2017 Jan 11.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Biogen
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Natalizumab (BG00002) in people with Multiple Sclerosis, run by Biogen at 17 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Oct 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A: Number of Participants With Adverse Events (AEs) (time frame: Baseline (Week 0) to Week 24). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01440101, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2014.