Clinical trial NCT00559702: Safety Study of Natalizumab to Treat Multiple Sclerosis (MS)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Relapsing-Remitting Multiple Sclerosis
Secondary Progressive Multiple Sclerosis
Keywords: natalizumab
multiple sclerosis
Tysabri ®
Lead sponsor: Biogen
Sponsor class: INDUSTRY
Collaborators: name: Elan Pharmaceuticals
First posted: 2007-11-16
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Maximum observed concentration (Cmax) of natalizumab
timeFrame: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56
measure: Time to maximum observed concentration (Tmax) of natalizumab
timeFrame: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56
measure: Area under the curve to the last measurable concentration (AUC0-last) of natalizumab
timeFrame: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56
measure: Apparent volume of distribution of natalizumab
timeFrame: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56
measure: Half-life of natalizumab
timeFrame: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56
measure: Area under the curve extrapolated to infinity (AUC0-∞) of natalizumab
timeFrame: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56
measure: Apparent Clearance of natalizumab
timeFrame: Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56
measure: α4-integrin saturation
timeFrame: Pre-dose, 4, 24 and 72 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56
Secondary outcomes:
measure: Number of Participants with adverse events
timeFrame: 13-19 months
measure: Number of participants with abnormalities in vital signs
timeFrame: 13-19 months
measure: Number of participants with changes in the physical examination
timeFrame: 13-19 months
measure: Number of participants with abnormal laboratory test results
timeFrame: 13-19 months
measure: Number of participants with natalizumab antibodies
timeFrame: Days 28, 42, 56, Weeks 24 and 32
measure: Change from Baseline in expanded disability status scale (EDSS)
timeFrame: Baseline, Weeks 8, 20, and 32
measure: Change form Baseline in Multiple Sclerosis Functional Composite Scale (MFSC)
timeFrame: Baseline, Weeks 8, 20, and 32
measure: Change from Baseline in Symbol Digit Modalities Test (SDMT)
timeFrame: Baseline, Weeks 8, 20, and 32
measure: Change from Baseline in visual analog scale (VAS)
timeFrame: Baseline, Weeks 8, 20, and 32
measure: Change from Baseline in visual function test
timeFrame: Baseline, Weeks 8, 20, and 32
measure: Number of new or newly enlarging T2 hyperintense lesions
timeFrame: Baseline and Week 32
measure: Number of new gadolinium-enhanced lesions
timeFrame: Baseline and Week 32
measure: Number of new T1 hypointense lesions
timeFrame: Baseline and Week 32
measure: Whole brain atrophy
timeFrame: Baseline and Week 32
measure: Percent change in magnetization transfer ratio (MTR)
timeFrame: Baseline and Week 32
measure: Diffusion tensor imaging (DTI)
timeFrame: Baseline and Week 32
measure: Injection site pain assessment
timeFrame: Pre-dose, 5 and 15 minutes and 24 hours post-dose
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Scottsdale
country: United States
facility: Research Site
state: Arizona
city: Berkeley
country: United States
facility: Research Site
state: California
city: Centennial
country: United States
facility: Research Site
state: Colorado
city: Maitland
country: United States
facility: Research Site
state: Florida
city: Vero Beach
country: United States
facility: Research Site
state: Florida
city: Peoria
country: United States
facility: Research Site
state: Illinois
city: Farmington Hills
country: United States
facility: Research Site
state: Michigan
city: Buffalo
country: United States
facility: Research Site
state: New York
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Round Rock
country: United States
facility: Research Site
state: Texas
city: Vienna
country: United States
facility: Research Site
state: Virginia
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: