Safety Study of Natalizumab to Treat Multiple Sclerosis (MS)

This study has been completed.
Sponsor:
Collaborator:
Elan Pharmaceuticals
Information provided by (Responsible Party):
Biogen Idec
ClinicalTrials.gov Identifier:
NCT00559702
First received: November 7, 2007
Last updated: September 5, 2014
Last verified: September 2014
  Purpose

The primary objective of this study is to compare the pharmacokinetic (PK) and pharmacodynamics (PD) of single subcutaneous (SC) and intramuscular (IM) doses of 300 mg natalizumab to intravenous (IV) administration of 300 mg natalizumab in multiple sclerosis (MS) participants. The secondary objectives are to investigate the safety, tolerability and PK of repeated natalizumab doses administered SC and IM, to investigate the immunogenicity of repeated natalizumab doses administered SC and IM, to explore proof of concept within the secondary progressive multiple sclerosis (SPMS) population using change from baseline in clinical measures including: expanded disability status scale (EDSS), multiple sclerosis functional composite scale (MSFC), symbol digit modalities test (SDMT), visual analogue scale (VAS), and visual function test; and brain magnetic resonance imaging (MRI) measures including: number of new or newly-enlarging T2 hyperintense lesions, number of new T1 hypointense lesions, number of new gadolinium-enhancing (Gd+) lesions, whole brain atrophy, magnetization transfer ratio (MTR), and diffusion tensor imaging (DTI) and to observe the effect of natalizumab administered IV and SC on brain MRI measures in participants with relapsing forms of MS.


Condition Intervention Phase
Relapsing-Remitting Multiple Sclerosis
Secondary Progressive Multiple Sclerosis
Drug: natalizumab
Other: standard of care
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open-Label, Dose-Ranging Study to Evaluate the Pharmacokinetics and Initial Safety of Subcutaneous and Intramuscular Natalizumab in Subjects With Multiple Sclerosis

Resource links provided by NLM:


Further study details as provided by Biogen Idec:

Primary Outcome Measures:
  • Maximum observed concentration (Cmax) of natalizumab [ Time Frame: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56 ] [ Designated as safety issue: No ]
  • Time to maximum observed concentration (Tmax) of natalizumab [ Time Frame: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56 ] [ Designated as safety issue: No ]
  • Area under the curve to the last measurable concentration (AUC0-last) of natalizumab [ Time Frame: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56 ] [ Designated as safety issue: No ]
    Area under the curve to the last measurable concentration as measured by the trapezoidal rule.

  • Apparent volume of distribution of natalizumab [ Time Frame: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56 ] [ Designated as safety issue: No ]
  • Half-life of natalizumab [ Time Frame: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56 ] [ Designated as safety issue: No ]
  • Area under the curve extrapolated to infinity (AUC0-∞) of natalizumab [ Time Frame: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56 ] [ Designated as safety issue: No ]
  • Apparent Clearance of natalizumab [ Time Frame: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56 ] [ Designated as safety issue: No ]
  • α4-integrin saturation [ Time Frame: Pre-dose, 4, 24 and 72 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56 ] [ Designated as safety issue: No ]
    PD activity will be assessed by measuring the degree of natalizumab saturation of the very late antigen-4 (also known as α4β1 integrin) VLA-4 (α4β1) receptor on peripheral blood lymphocyte/monocyte populations.


Secondary Outcome Measures:
  • Number of Participants with adverse events [ Time Frame: 13-19 months ] [ Designated as safety issue: Yes ]
  • Number of participants with abnormalities in vital signs [ Time Frame: 13-19 months ] [ Designated as safety issue: Yes ]
  • Number of participants with changes in the physical examination [ Time Frame: 13-19 months ] [ Designated as safety issue: Yes ]
  • Number of participants with abnormal laboratory test results [ Time Frame: 13-19 months ] [ Designated as safety issue: Yes ]
  • Number of participants with natalizumab antibodies [ Time Frame: Days 28, 42, 56, Weeks 24 and 32 ] [ Designated as safety issue: Yes ]
  • Change from Baseline in expanded disability status scale (EDSS) [ Time Frame: Baseline, Weeks 8, 20, and 32 ] [ Designated as safety issue: No ]
    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.

  • Change form Baseline in Multiple Sclerosis Functional Composite Scale (MFSC) [ Time Frame: Baseline, Weeks 8, 20, and 32 ] [ Designated as safety issue: No ]
    The MFSC consists of 3 tests: 1. Timed 25-Foot Walk, a quantitative mobility and leg function performance test where the participant is timed while walking for 25 feet; 2. 9-Hole Peg Test (9HPT), a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs. 3. 3 Second Paced Auditory Serial Addition Test (PASAT 3). The MSFC is based on the concept that scores for these 3 dimensions - arm, leg, and cognitive function are combined to create a single score that can be used to detect change over time. A composite z-score is created, which represents the number of standard deviations (SDs) a participant's test result is higher (z > 0) or lower (z < 0) than the average test result (z = 0) of the reference population.

  • Change from Baseline in Symbol Digit Modalities Test (SDMT) [ Time Frame: Baseline, Weeks 8, 20, and 32 ] [ Designated as safety issue: No ]
    SDMT is a screening test for cognitive impairment. Participants are given 90 seconds in which to pair specific numbers with given geometric figures using a key. Scores range from 0 to 110 (best).

  • Change from Baseline in visual analog scale (VAS) [ Time Frame: Baseline, Weeks 8, 20, and 32 ] [ Designated as safety issue: No ]
    The participant's global assessment of well-being as assessed using a visual analogue scale (VAS) is a quality of life measurement that will be evaluated for the specified time periods. Participants report how they feel on a scale of 0 to 100, where 0 indicates being "poor" and 100 being "excellent."

  • Change from Baseline in visual function test [ Time Frame: Baseline, Weeks 8, 20, and 32 ] [ Designated as safety issue: No ]
  • Number of new or newly enlarging T2 hyperintense lesions [ Time Frame: Baseline and Week 32 ] [ Designated as safety issue: No ]
    Measured by magnetic resonance imaging (MRI).

  • Number of new gadolinium-enhanced lesions [ Time Frame: Baseline and Week 32 ] [ Designated as safety issue: No ]
    Measured by magnetic resonance imaging (MRI).

  • Number of new T1 hypointense lesions [ Time Frame: Baseline and Week 32 ] [ Designated as safety issue: No ]
    Measured by magnetic resonance imaging (MRI).

  • Whole brain atrophy [ Time Frame: Baseline and Week 32 ] [ Designated as safety issue: No ]
    Atrophy will be measured as the percent brain volume change (PBVC) and will be assessed using the Structural Image Evaluation of Normalized Atrophy (SIENA).

  • Percent change in magnetization transfer ratio (MTR) [ Time Frame: Baseline and Week 32 ] [ Designated as safety issue: No ]
    Remyelination will be measured using magnetization transfer ratio (MTR) in whole brain (WB) and normal-appearing brain tissue (NABT),

  • Diffusion tensor imaging (DTI) [ Time Frame: Baseline and Week 32 ] [ Designated as safety issue: No ]
  • Injection site pain assessment [ Time Frame: Pre-dose, 5 and 15 minutes and 24 hours post-dose ] [ Designated as safety issue: No ]

Enrollment: 76
Study Start Date: October 2007
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Natalizumab IV (Participants with secondary progressive multiple sclerosis)
Drug: natalizumab
natalizumab
Other Names:
  • Tysabri ®
  • BG00002
Experimental: 2
Natalizumab IM (Participants with secondary progressive multiple sclerosis)
Drug: natalizumab
natalizumab
Other Names:
  • Tysabri ®
  • BG00002
Experimental: 3
Natalizumab SC (Participants with secondary progressive multiple sclerosis)
Drug: natalizumab
natalizumab
Other Names:
  • Tysabri ®
  • BG00002
4
Standard of care as determined by the Investigator and Treating Neurologist (Participants with secondary progressive multiple sclerosis)
Other: standard of care
standard of care as determined by the Investigator and Treating Neurologist
Experimental: 5
Natalizumab SC (Participants with relapsing forms of multiple sclerosis)
Drug: natalizumab
natalizumab
Other Names:
  • Tysabri ®
  • BG00002
Experimental: 6
Natalizumab IV (Participants with relapsing forms of multiple sclerosis)
Drug: natalizumab
natalizumab
Other Names:
  • Tysabri ®
  • BG00002

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • For arms 1,2,3 and 4: Diagnosis of Secondary Progressive Multiple Sclerosis (SPMS)
  • For arms 5 and 6: Diagnosis of relapsing forms of Multiple Sclerosis (MS).
  • No past history of receiving natalizumab.

Key Exclusion Criteria:

  • For arms 1,2,3 and 4 Diagnosis of primary progressive MS or relapsing-remitting MS.
  • Form arms 5 and 6: Diagnosis of primary progressive MS or secondary progressive MS without the occurrence of relapses.

NOTE: Other protocol defined inclusion/exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00559702

Locations
United States, Arizona
Research Site
Phoenix, Arizona, United States, 85006
Research Site
Scottsdale, Arizona, United States, 85259
United States, California
Research Site
Berkeley, California, United States, 94705
United States, Colorado
Research Site
Centennial, Colorado, United States, 80112
United States, Florida
Research Site
Maitland, Florida, United States, 32751
Research Site
Vero Beach, Florida, United States, 32960
United States, Illinois
Research Site
Peoria, Illinois, United States, 61637
United States, Michigan
Research Site
Farmington Hills, Michigan, United States, 48334
United States, New York
Research Site
Buffalo, New York, United States, 14203
United States, Texas
Research Site
Dallas, Texas, United States, 75214
Research Site
Round Rock, Texas, United States, 78681
United States, Virginia
Research Site
Vienna, Virginia, United States, 22182
Sponsors and Collaborators
Biogen Idec
Elan Pharmaceuticals
Investigators
Study Director: Medical Director Biogen Idec
  More Information

No publications provided

Responsible Party: Biogen Idec
ClinicalTrials.gov Identifier: NCT00559702     History of Changes
Other Study ID Numbers: 101MS102
Study First Received: November 7, 2007
Last Updated: September 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Biogen Idec:
natalizumab
multiple sclerosis
Tysabri ®

Additional relevant MeSH terms:
Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Multiple Sclerosis, Chronic Progressive
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on October 19, 2014