PK and PD Study of Natalizumab in Pediatric Subjects With RRMS

Study Overview
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Brief Summary
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The primary objective of the study is to determine the pharmacokinetic (PK) profile of multiple doses of natalizumab in pediatric subjects with relapsing-remitting multiple sclerosis (RRMS). The secondary objectives are as follows: to characterize the pharmacodynamic (PD) profile of natalizumab (as defined by α4 integrin binding) and to explore the safety and tolerability of multiple doses of natalizumab in the pediatric population.

Official Title
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A Phase 1, Multicenter, Open-Label, Single-Arm, Multiple Dose Study to Evaluate the the Pharmacokinetics and Pharmacodynamics of Natalizumab in Pediatric Subjects With Relapsing Remitting Multiple Sclerosis (RMS)

Conditions
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Relapsing-Remitting Multiple Sclerosis

Intervention / Treatment
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* Biological: Natalizumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: - Rapidly evolving severe relapsing remitting multiple sclerosis, defined by 2 or more disabling relapses in 1 year, and with 1 or more gadolinium-enhancing lesions on brain MRI or a significant increase in T2 lesion load, as compared to a previous recent magnetic resonance imaging (MRI) Key Exclusion Criteria: History of, or abnormal laboratory values indicative of, significant medical, neurologic (other than MS), or psychiatric disorders that might preclude participation in the study in the opinion of the Investigator. Prior natalizumab therapy. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Natalizumab<br>300 mg intravenously (IV) every 4 weeks | Biological: Natalizumab<br>* As specified in the treatment arm<br>* Other names: BG00002;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| predose (trough) concentrations from multiple dosing (Cpredose) |  | Up to week 16 | 
| maximum plasma concentration (Cmax) |  | Up to Week 16 | 
| time to maximum plasma concentration (Tmax) |  | Up to Week 16 | 
| area under the plasma concentration curve from time of first dose to infinity (AUCinf) |  | Up to Week 16 | 
| apparent clearance (Cl/F) |  | Up to Week 16 | 
| volume of distribution |  | Up to Week 16 | 
| elimination half-life (t1/2) |  | Up to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the average and minimum saturation values of α4 integrin over the dosing interval |  | Up to Week 16 | 
| incidence of serious adverse events (SAEs), infusion and hypersensitivity reactions, and other AEs |  | Up to Week 16 | 
| the presence of anti-natalizumab antibodies |  | Up to Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatric