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Safety Study of Natalizumab to Treat Multiple Sclerosis (MS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00559702
Recruitment Status : Completed
First Posted : November 16, 2007
Last Update Posted : September 9, 2014
Sponsor:
Collaborator:
Elan Pharmaceuticals
Information provided by (Responsible Party):
Biogen

Tracking Information
First Submitted Date  ICMJE November 7, 2007
First Posted Date  ICMJE November 16, 2007
Last Update Posted Date September 9, 2014
Study Start Date  ICMJE October 2007
Actual Primary Completion Date November 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 5, 2014)
  • 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 ]
  • 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 ]
  • 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 ]
    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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • α4-integrin saturation [ Time Frame: Pre-dose, 4, 24 and 72 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56 ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 14, 2007)
PK, PD [ Time Frame: 32 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 5, 2014)
  • Number of Participants with adverse events [ Time Frame: 13-19 months ]
  • Number of participants with abnormalities in vital signs [ Time Frame: 13-19 months ]
  • Number of participants with changes in the physical examination [ Time Frame: 13-19 months ]
  • Number of participants with abnormal laboratory test results [ Time Frame: 13-19 months ]
  • Number of participants with natalizumab antibodies [ Time Frame: Days 28, 42, 56, Weeks 24 and 32 ]
  • Change from Baseline in expanded disability status scale (EDSS) [ Time Frame: Baseline, Weeks 8, 20, and 32 ]
    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 ]
    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 ]
    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 ]
    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 ]
  • Number of new or newly enlarging T2 hyperintense lesions [ Time Frame: Baseline and Week 32 ]
    Measured by magnetic resonance imaging (MRI).
  • Number of new gadolinium-enhanced lesions [ Time Frame: Baseline and Week 32 ]
    Measured by magnetic resonance imaging (MRI).
  • Number of new T1 hypointense lesions [ Time Frame: Baseline and Week 32 ]
    Measured by magnetic resonance imaging (MRI).
  • Whole brain atrophy [ Time Frame: Baseline and Week 32 ]
    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 ]
    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 ]
  • Injection site pain assessment [ Time Frame: Pre-dose, 5 and 15 minutes and 24 hours post-dose ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 14, 2007)
  • safety [ Time Frame: 32 weeks ]
  • efficacy [ Time Frame: 32 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety Study of Natalizumab to Treat Multiple Sclerosis (MS)
Official Title  ICMJE A Randomized, Open-Label, Dose-Ranging Study to Evaluate the Pharmacokinetics and Initial Safety of Subcutaneous and Intramuscular Natalizumab in Subjects With Multiple Sclerosis
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Relapsing-Remitting Multiple Sclerosis
  • Secondary Progressive Multiple Sclerosis
Intervention  ICMJE
  • Drug: natalizumab
    natalizumab
    Other Names:
    • Tysabri ®
    • BG00002
  • Other: standard of care
    standard of care as determined by the Investigator and Treating Neurologist
Study Arms  ICMJE
  • Experimental: 1
    Natalizumab IV (Participants with secondary progressive multiple sclerosis)
    Intervention: Drug: natalizumab
  • Experimental: 2
    Natalizumab IM (Participants with secondary progressive multiple sclerosis)
    Intervention: Drug: natalizumab
  • Experimental: 3
    Natalizumab SC (Participants with secondary progressive multiple sclerosis)
    Intervention: Drug: natalizumab
  • 4
    Standard of care as determined by the Investigator and Treating Neurologist (Participants with secondary progressive multiple sclerosis)
    Intervention: Other: standard of care
  • Experimental: 5
    Natalizumab SC (Participants with relapsing forms of multiple sclerosis)
    Intervention: Drug: natalizumab
  • Experimental: 6
    Natalizumab IV (Participants with relapsing forms of multiple sclerosis)
    Intervention: Drug: natalizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 17, 2011)
76
Original Estimated Enrollment  ICMJE
 (submitted: November 14, 2007)
72
Actual Study Completion Date  ICMJE November 2011
Actual Primary Completion Date November 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00559702
Other Study ID Numbers  ICMJE 101MS102
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Biogen
Original Responsible Party Not Provided
Current Study Sponsor  ICMJE Biogen
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Elan Pharmaceuticals
Investigators  ICMJE
Study Director: Medical Director Biogen
PRS Account Biogen
Verification Date September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP