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A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Participants With Secondary Progressive Multiple Sclerosis

Information source: Biogen
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Secondary Progressive Multiple Sclerosis

Intervention: natalizumab (Drug); Placebo (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Biogen

Official(s) and/or principal investigator(s):
Medical Director, Study Director, Affiliation: Biogen

Summary

This is a Phase 3b, multicenter, international study conducted in 2 parts. Upon completion of the placebo-controlled period (Part 1), participants will have the option of enrolling in a 2-year open-label extension (Part 2). Part 1: The primary objective of the study is to investigate whether treatment with natalizumab slows the accumulation of disability not related to relapses in participants with secondary progressive multiple sclerosis (SPMS). The secondary objectives of Part 1 of this study are to determine the proportion of participants with consistent improvement in Timed 25-Foot Walk (T25FW), the change in participant-reported ambulatory status as measured by the 12-item MS Walking Scale (MSWS-12), the change in manual ability based on the ABILHAND Questionnaire, the impact of natalizumab on participant-reported quality of life using the Multiple Sclerosis Impact Scale-29 Physical (MSIS-29 Physical), the change in whole brain volume between the end of study and Week 24 using magnetic resonance imaging (MRI) and the proportion of participants experiencing progression of disability as measured by individual physical Expanded Disability Status Scale (EDSS) system scores. Part 2: The primary objective of Part 2 of the study is to evaluate the safety profile of natalizumab in participants with SPMS. The secondary objectives of Part 2 of the study are to investigate long-term disability (based on clinical or patient-reported assessments) in participants with SPMS receiving natalizumab treatment for approximately 4 years and to assess change in brain volume and T2 lesion volume.

Clinical Details

Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy of Natalizumab on Reducing Disability Progression in Subjects With Secondary Progressive Multiple Sclerosis, With Optional Open-Label Extension

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Primary outcome:

Part 1: Percentage of participants with confirmed progression of disability in one or more of the Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), or 9-Hole Peg Test (9HPT)

The number of participants with Adverse Events (AE) and Serious Adverse Events (SAE)

Secondary outcome:

Part 1: Percentage of participants with a Timed 25-Foot Walk (T25FW) response

Part 1: Change from Baseline in the 12-Item MS Walking Scale (MSWS-12)

Part 1: Change from Baseline in manual ability score based on the ABILHAND Questionnaire

Part 1: Change from Baseline in the Multiple Sclerosis Impact Scale-29 Physical (MSIS-29 Physical) score

Part 1: Change from Week 24 in whole brain volume

Part 1: Percentage of participants with confirmed worsening in individual Expanded Disability Status Scale (EDSS) Physical Functional System scores

Part 2: Percentage of participants with disability worsening

Part 2: Absolute change from Baseline (Part 1) in Timed 25-Foot Walk (T25FW)

Part 2: Percentage change from Baseline (Part 2) in Timed 25-Foot Walk (T25FW)

Part 2: Absolute change from Baseline (Part 1) in 9-Hole Peg Test (9HPT)

Part 2: Percentage change from Baseline (Part 1) in 9-Hole Peg Test (9HPT)

Part 2: Absolute change from Baseline (Part 1) in Expanded Disability Status Scale (EDSS)

Part 2: Percentage change from Baseline (Part 1) in Expanded Disability Status Scale (EDSS)

Part 2: Absolute change from Baseline (Part 1) in the 6-Minute Walk Test (6MWT)

Part 2: Percentage change from Baseline (Part 1) in the 6-Minute Walk Test (6MWT)

Part 2: Absolute change from Baseline (Part 1) in the Multiple Sclerosis Impact Scale-29 Physical (MSIS-29 Physical)

Part 2: Percentage change from Baseline (Part 1) in the Multiple Sclerosis Impact Scale-29 Physical (MSIS-29 Physical)

Part 2: Absolute change from Baseline (Part 1) in the Symbol Digit Modalities Test (SDMT)

Part 2: Percentage change from Baseline (Part 1) in the Symbol Digit Modalities Test (SDMT)

Part 2: Absolute change from Baseline (Part 2) in the Work Productivity and Activity Impairment - Multiple Sclerosis (WPAI-MS) Questionnaire

Part 2: Percentage change from Baseline (Part 2) in the Work Productivity and Activity Impairment - Multiple Sclerosis (WPAI-MS) Questionnaire

Part 2: Percentage change from Baseline (Part 1) in whole brain volume

Part 2: Percentage change from Baseline (Part 1) in gray matter brain volume

Part 2: Absolute change from Baseline (Part 1) in number of new/enlarging T2 lesions

Part 2: Percentage change from Baseline (Part 1) in number of new/enlarging T2 lesions

Eligibility

Minimum age: 18 Years. Maximum age: 58 Years. Gender(s): Both.

Criteria:

Key Inclusion Criteria (Part 1):

- Ability to understand the purpose and risks of the study and provide signed and dated

informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.

- Secondary progressive multiple sclerosis (SPMS) defined as relapsing-remitting

disease followed by progression of disability independent of or not explained by multiple sclerosis (MS) relapses for at least 2 years.

- Expanded Disability Status Scale (EDSS) score of 3. 0 to 6. 5, inclusive.

- Multiple Sclerosis Severity Score (MSSS) of 4 or higher.

- Documented confirmed evidence of disease progression independent of clinical relapses

over the 1 year prior to enrollment as defined in the Study Reference Guide. Key Exclusion Criteria (Part 1):

- Relapsing remitting multiple sclerosis (RRMS) or primary progressive multiple

sclerosis (MS) as defined by the revised McDonald Committee criteria.

- Clinical relapse (within 3 months) prior to randomization.

- Timed 25-Foot Walk (T25FW) test of >30 seconds during the screening period.

- Any value below the lower limit of normal for blood levels of leukocytes,

lymphocytes, or neutrophils.

- Considered by the Investigator to be immunocompromised based on medical history,

physical examination, laboratory testing, or any other testing required by local guidelines, or due to prior immunosuppressive or immunomodulating treatment.

- Subjects for whom magnetic resonance imaging (MRI) is contraindicated (i. e., have

pacemakers or other contraindicated implanted metal devices, are allergic to gadolinium, or have claustrophobia that cannot be medically managed).

- History of any clinically significant (as determined by the Investigator) cardiac,

endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic (other than MS), dermatologic, psychiatric, and renal, or other major disease that would preclude participation in a clinical study.

- History of malignant disease, including solid tumors and hematologic malignancies

(with the exception of basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured).

- Known history of or positive test result for Human Immunodeficiency Virus (HIV).

- Positive test result for hepatitis C virus (test for hepatitis C virus antibody [HCV

Ab]) or hepatitis B virus (test for hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [HBcAb]).

- History of transplantation or any anti-rejection therapy.

- Presence of any infectious disease (e. g., cellulitis, abscess, pneumonia, septicemia)

within 30 days prior to screening.

- History of progressive multifocal leukoencephalopathy (PML) or other opportunistic

infections. Treatment History (Part 1)

- Any prior treatment with cell-depleting therapies, including total lymphoid

irradiation, cladribine, rituximab, alemtuzumab, or bone marrow ablation.

- Any prior treatment with natalizumab.

- Treatment with mitoxantrone, cyclophosphamide, cyclosporine, azathioprine,

methotrexate, mycophenolate mofetil, T cell or T cell receptor vaccination, fingolimod, daclizumab, or cytapheresis within 6 months prior to randomization.

- Treatment with intravenous or oral corticosteroids, intravenous immunoglobulin

(IVIg), or plasmapheresis for treatment of multiple sclerosis within the 3 months prior to randomization.

- Treatment with glatiramer acetate or any interferon beta preparations within 4 weeks

prior to randomization.

- Treatment with 4-aminopyridine within 30 days prior to randomization, unless a stable

dose has been maintained for at least 30 days prior to randomization and will be continued for the course of this study. Key Inclusion Criteria (Part 2):

- Subjects must have participated in and completed Part 1 per protocol, and have

documented assessment attempts for Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT) prior to first open-label dosing. Key Exclusion Criteria (Part 2):

- Subjects with any significant change in clinical status, including laboratory tests

that, in the opinion of the Investigator, would make them unsuitable to participate in this extension study. The Investigator must re-review the subject's medical fitness for participation and consider any diseases that would preclude treatment.

- Subjects who discontinued study treatment in Part 1 OR had fewer than 20 infusions in

Part 1 OR missed 2 or more consecutive infusions in Part 1. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Locations and Contacts

Research Site, La Louviere, Belgium

Research Site, Melsbroek, Belgium

Research Site, Overpelt, Belgium

Research Site, Brno, Czech Republic

Research Site, Olomouc, Czech Republic

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Research Site, Arthus C, Denmark

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Additional Information

Find out what to expect with TYSABRI MS treatment

Starting date: September 2011
Last updated: August 20, 2015

Page last updated: August 23, 2015

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