Safety Study of Natalizumab to Treat Multiple Sclerosis (MS)

NCT00559702 | Completed Phase 1

• 1 other identifier: 101MS102
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 12

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.

Conditions

Relapsing-Remitting Multiple Sclerosis; Secondary Progressive Multiple Sclerosis

Keywords

natalizumab; multiple sclerosis; Tysabri ®

Outcome Measures

Primary Outcomes (8)

• 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

• 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

• 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

• 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

• 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

• Area under the curve extrapolated to infinity (AUC0-∞) of natalizumab

  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

  Pre-dose, 4, 24, 48, 72 and 96 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56

• α4-integrin saturation

  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.

  Pre-dose, 4, 24 and 72 hours post-dose and Days 7, 14, 21, 28, 35, 42 and 56

Secondary Outcomes (17)

• Number of Participants with adverse events

  13-19 months

• Number of participants with abnormalities in vital signs

  13-19 months

• Number of participants with changes in the physical examination

  13-19 months

• Number of participants with abnormal laboratory test results

  13-19 months

• Number of participants with natalizumab antibodies

  Days 28, 42, 56, Weeks 24 and 32

Study Arms (6)

1

EXPERIMENTAL

Natalizumab IV (Participants with secondary progressive multiple sclerosis)

Drug: natalizumab

2

EXPERIMENTAL

Natalizumab IM (Participants with secondary progressive multiple sclerosis)

Drug: natalizumab

3

EXPERIMENTAL

Natalizumab SC (Participants with secondary progressive multiple sclerosis)

Drug: natalizumab

4

OTHER

Standard of care as determined by the Investigator and Treating Neurologist (Participants with secondary progressive multiple sclerosis)

Other: standard of care

5

EXPERIMENTAL

Natalizumab SC (Participants with relapsing forms of multiple sclerosis)

Drug: natalizumab

6

EXPERIMENTAL

Natalizumab IV (Participants with relapsing forms of multiple sclerosis)

Drug: natalizumab

Interventions

natalizumab DRUG

natalizumab

Also known as: Tysabri ®, BG00002

1; 2; 3; 5; 6

standard of care OTHER

standard of care as determined by the Investigator and Treating Neurologist

4

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Biogen: lead
• Elan Pharmaceuticals: collaborator

Study Sites (12)

Research Site

Phoenix, Arizona, 85006, United States

Location

Research Site

Scottsdale, Arizona, 85259, United States

Location

Research Site

Berkeley, California, 94705, United States

Location

Research Site

Centennial, Colorado, 80112, United States

Location

Research Site

Maitland, Florida, 32751, United States

Location

Research Site

Vero Beach, Florida, 32960, United States

Location

Research Site

Peoria, Illinois, 61637, United States

Location

Research Site

Farmington Hills, Michigan, 48334, United States

Location

Research Site

Buffalo, New York, 14203, United States

Location

Research Site

Dallas, Texas, 75214, United States

Location

Research Site

Round Rock, Texas, 78681, United States

Location

Research Site

Vienna, Virginia, 22182, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis

Interventions

Natalizumab; Standard of Care

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2007
• First Posted: November 16, 2007
• Study Start: October 1, 2007
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: September 9, 2014

Record last verified: 2014-09

Locations

US (12)