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Completed

NCT Number: NCT00559702

Safety Study of Natalizumab to Treat Multiple Sclerosis (MS)

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.

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Key information

Conditions

Relapsing-Remitting Multiple Sclerosis Autoimmune Diseases Autoimmune Diseases of the Nervous System Chronic Disease Demyelinating Autoimmune Diseases, CNS Demyelinating Diseases Disease Attributes Immune System Diseases Multiple Sclerosis Multiple Sclerosis, Chronic Progressive Multiple Sclerosis, Relapsing-Remitting Nervous System Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Secondary Progressive Multiple Sclerosis

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Research Site, Phoenix, Arizona, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Natalizumab

Drug

natalizumab

Other names: Tysabri ®, BG00002

Standard of care

Other

standard of care as determined by the Investigator and Treating Neurologist

Primary outcomes

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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.

Secondary outcomes

  1. Number of Participants with adverse events

    Time frame: 13-19 months

  2. Number of participants with abnormalities in vital signs

    Time frame: 13-19 months

  3. Number of participants with changes in the physical examination

    Time frame: 13-19 months

  4. Number of participants with abnormal laboratory test results

    Time frame: 13-19 months

  5. Number of participants with natalizumab antibodies

    Time frame: Days 28, 42, 56, Weeks 24 and 32

  6. 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.

  7. 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.

  8. 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).

  9. 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."

  10. Change from Baseline in visual function test

    Time frame: Baseline, Weeks 8, 20, and 32

  11. Number of new or newly enlarging T2 hyperintense lesions

    Time frame: Baseline and Week 32

    Measured by magnetic resonance imaging (MRI).

  12. Number of new gadolinium-enhanced lesions

    Time frame: Baseline and Week 32

    Measured by magnetic resonance imaging (MRI).

  13. Number of new T1 hypointense lesions

    Time frame: Baseline and Week 32

    Measured by magnetic resonance imaging (MRI).

  14. 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).

  15. 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),

  16. Diffusion tensor imaging (DTI)

    Time frame: Baseline and Week 32

  17. Injection site pain assessment

    Time frame: Pre-dose, 5 and 15 minutes and 24 hours post-dose

Sponsors and collaborators

Lead sponsor

Biogen

Industry

Collaborators

  • Elan Pharmaceuticals

Registry information

Official study 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

Important dates

Study start
2007
Primary completion
2011
Study completion
2011
First posted
Nov 16, 2007
Registry last updated
Sep 9, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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