Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00559702
Other study ID # 101MS102
Secondary ID
Status Completed
Phase Phase 1
First received November 7, 2007
Last updated September 5, 2014
Start date October 2007
Est. completion date November 2011

Study information

Verified date September 2014
Source Biogen
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 76
Est. completion date November 2011
Est. primary completion date November 2011
Accepts healthy volunteers No
Gender Both
Age group 18 Years to 65 Years
Eligibility 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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms

  • Multiple Sclerosis
  • Multiple Sclerosis, Chronic Progressive
  • Multiple Sclerosis, Relapsing-Remitting
  • Relapsing-Remitting Multiple Sclerosis
  • Sclerosis
  • Secondary Progressive Multiple Sclerosis

Intervention

Drug:
natalizumab
natalizumab
Other:
standard of care
standard of care as determined by the Investigator and Treating Neurologist

Locations

Country Name City State
United States Research Site Berkeley California
United States Research Site Buffalo New York
United States Research Site Centennial Colorado
United States Research Site Dallas Texas
United States Research Site Farmington Hills Michigan
United States Research Site Maitland Florida
United States Research Site Peoria Illinois
United States Research Site Phoenix Arizona
United States Research Site Round Rock Texas
United States Research Site Scottsdale Arizona
United States Research Site Vero Beach Florida
United States Research Site Vienna Virginia

Sponsors (2)

Lead Sponsor Collaborator
Biogen Elan Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Maximum observed concentration (Cmax) of natalizumab Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56 No
Primary Time to maximum observed concentration (Tmax) of natalizumab Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56 No
Primary Area under the curve to the last measurable concentration (AUC0-last) of natalizumab Area under the curve to the last measurable concentration as measured by the trapezoidal rule. Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56 No
Primary Apparent volume of distribution of natalizumab Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56 No
Primary Half-life of natalizumab Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56 No
Primary Area under the curve extrapolated to infinity (AUC0-8) of natalizumab Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56 No
Primary Apparent Clearance of natalizumab Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56 No
Primary a4-integrin saturation PD activity will be assessed by measuring the degree of natalizumab saturation of the very late antigen-4 (also known as a4ß1 integrin) VLA-4 (a4ß1) receptor on peripheral blood lymphocyte/monocyte populations. Pre-dose, 4, 24 and 72 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56 No
Secondary Number of Participants with adverse events 13-19 months Yes
Secondary Number of participants with abnormalities in vital signs 13-19 months Yes
Secondary Number of participants with changes in the physical examination 13-19 months Yes
Secondary Number of participants with abnormal laboratory test results 13-19 months Yes
Secondary Number of participants with natalizumab antibodies Days 28, 42, 56, Weeks 24 and 32 Yes
Secondary Change from Baseline in expanded disability status scale (EDSS) 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. Baseline, Weeks 8, 20, and 32 No
Secondary Change form Baseline in Multiple Sclerosis Functional Composite Scale (MFSC) 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. Baseline, Weeks 8, 20, and 32 No
Secondary Change from Baseline in Symbol Digit Modalities Test (SDMT) 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). Baseline, Weeks 8, 20, and 32 No
Secondary Change from Baseline in visual analog scale (VAS) 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." Baseline, Weeks 8, 20, and 32 No
Secondary Change from Baseline in visual function test Baseline, Weeks 8, 20, and 32 No
Secondary Number of new or newly enlarging T2 hyperintense lesions Measured by magnetic resonance imaging (MRI). Baseline and Week 32 No
Secondary Number of new gadolinium-enhanced lesions Measured by magnetic resonance imaging (MRI). Baseline and Week 32 No
Secondary Number of new T1 hypointense lesions Measured by magnetic resonance imaging (MRI). Baseline and Week 32 No
Secondary Whole brain atrophy Atrophy will be measured as the percent brain volume change (PBVC) and will be assessed using the Structural Image Evaluation of Normalized Atrophy (SIENA). Baseline and Week 32 No
Secondary Percent change in magnetization transfer ratio (MTR) Remyelination will be measured using magnetization transfer ratio (MTR) in whole brain (WB) and normal-appearing brain tissue (NABT), Baseline and Week 32 No
Secondary Diffusion tensor imaging (DTI) Baseline and Week 32 No
Secondary Injection site pain assessment Pre-dose, 5 and 15 minutes and 24 hours post-dose No
See also
  Status Clinical Trial Phase
Completed NCT02549703 - Mitochondrial Dysfunction and Disease Progression
Completed NCT02293967 - Mass Balance Study of MT-1303 Phase 1
Terminated NCT02222948 - Efficacy and Safety of Vatelizumab in Patients With Relapsing-Remitting Multiple Sclerosis Phase 2
Terminated NCT01790269 - Monitoring Natural Killer Cells in Multiple Sclerosis Patients Treated With Fingolimod
Terminated NCT01701856 - Natalizumab De-escalation to Interferon-beta-1b in Patients With Relapsing-remitting Multiple Sclerosis Phase 4
Completed NCT00525668 - Sunphenon Epigallocatechin-gallate (EGCg) in Relapsing-remitting Multiple Sclerosis (SuniMS Study) Phase 1/Phase 2
Terminated NCT00398528 - An fMRI Study of Treatment Optimization Comparing Two Disease Modifying Therapies Used to Treat Relapsing Remitting Multiple Sclerosis Phase 4
Completed NCT00315367 - A fMRI(Functional Magnetic Resonance Imaging) Research Study to Learn More About Multiple Sclerosis and Individuals Potentially Experiencing Memory Difficulties Phase 4
Terminated NCT04032171 - Study of Evobrutinib in Participants With RMS Phase 3
Completed NCT01930708 - A Study Evaluating the Effectiveness of Tecfidera (Dimethyl Fumarate) on Multiple Sclerosis (MS) Disease Activity and Patient-Reported Outcomes Phase 4
Completed NCT03000647 - Guided Versus Non-guided Pelvic Floor Exercises for Urinary Incontinence in Relapsing-Remitting Multiple Sclerosis N/A
Completed NCT02205489 - Management Of The Infusion-Associated Reactions In RRMS Patients Treated With LEMTRADA Phase 4
Completed NCT02753088 - Efficacy and Safety of BCD-063 and Copaxone-Teva in Patients With Relapsing-Remitting Multiple Sclerosis Phase 3
Recruiting NCT01466114 - Estriol Treatment in Multiple Sclerosis (MS): Effect on Cognition Phase 2
Completed NCT01244139 - Safety Study of BIIB033 in Subjects With Multiple Sclerosis Phase 1
Completed NCT01416155 - Extension Study to Evaluate Safety and Efficacy of Natalizumab in Japanese Participants With Relapsing-Remitting Multiple Sclerosis Phase 2
Completed NCT00493116 - Is IFN-beta Treatment in MS Useful After a Washout Period in Patients With Neutralizing Antibodies to Interferon Beta Phase 4
Terminated NCT01706107 - Canadian Multicenter Observational Study of Tysabri in Early Relapsing Remitting Multiple Sclerosis Participants
Completed NCT01943526 - Ireland Natalizumab (TYSABRI) Observational Program
Terminated NCT02342704 - Impact of Natalizumab Versus Fingolimod in Relapsing-Remitting Multiple Sclerosis (RRMS) Participants Phase 4