Natalizumab (BG00002, Tysabri) Study in Japanese Participants With Relapsing-Remitting Multiple Sclerosis (RRMS)

NCT01440101 | Completed Phase 2 Results DMC

• 1 other identifier: 101MS203
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 17

Brief 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). 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.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Baseline (Week 0) to Week 24

Secondary Outcomes (17)

• Part B: Cumulative Number of New Active Lesions Over 24 Weeks

  Baseline (Week 0) to Week 24

• Part B: Adjusted Annualized Relapse Rate Over 24 Weeks

  Week 24

• Part B: Cumulative Number of Gd+ Lesions Over 24 Weeks

  Baseline (Week 0) to Week 24

• Part B: Cumulative Number Of New Or Newly Enlarging, Non-Enhancing T2-Hyperintense Lesions Over 24 Weeks

  Baseline (Week 0) to Week 24

• Part B: Number of Participants Who Were Relapse Free Over 24 Weeks

  Baseline (Week 0) to Week 24

Study Arms (3)

Double-blind Natalizumab 300 mg

EXPERIMENTAL

300 mg IV infusions of natalizumab over 60 minutes every 4 weeks for 20 weeks

Drug: Natalizumab (BG00002)

Double-blind Placebo

PLACEBO COMPARATOR

IV infusions of placebo over 60 minutes every 4 weeks for 20 weeks

Drug: Placebo

Open-label Natalizumab

EXPERIMENTAL

300 mg IV infusions of natalizumab over 60 minutes every 4 weeks for 20 weeks

Drug: Natalizumab (BG00002)

Interventions

Natalizumab (BG00002) DRUG

Also known as: Tysabri

Double-blind Natalizumab 300 mg; Open-label Natalizumab

Placebo DRUG

Double-blind Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Biogen: lead

Study Sites (17)

Research Site

Chiba, Japan

Location

Research Site

Fukuoka, Japan

Location

Research Site

Hiroshima, Japan

Location

Research Site

Kawagoe, Japan

Location

Research Site

Kyoto, Japan

Location

Research Site

Morioka, Japan

Location

Research Site

Niigata, Japan

Location

Research Site

Osaka, Japan

Location

Research Site

Otaku, Japan

Location

Research Site

Sapporo, Japan

Location

Research Site

Sendai, Japan

Location

Research Site

Suita, Japan

Location

Research Site

Tokorozawa, Japan

Location

Research Site

Tokyo, Japan

Location

Research Site

Tsukuba, Japan

Location

Research Site

Ube, Japan

Location

Research Site

Yokohama, Japan

Location

Related Publications (2)

• 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.

  PMID: 28104251 DERIVED

• Saida 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.

  PMID: 28078634 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Natalizumab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Biogen Idec Study Medical Director
• Organization: Biogen Idec

clinicaltrials@biogenidec.com

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2011
• First Posted: September 26, 2011
• Study Start: November 1, 2010
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: October 21, 2014
• Results First Posted: October 21, 2014

Record last verified: 2014-10

Locations

JP (17)