Clinical Trial: A Treatment Study of Mucopolysaccharidosis Type IIIB

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase 1/2 Open-Label Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Intracerebroventricular BMN 250 in Patients With Mucopolysaccharidosis Type IIIB (MP

Brief Summary: The study's primary objectives are to evaluate the safety and tolerability of BMN 250 administered to subjects with MPS IIIB via an ICV reservoir and catheter and to evaluate the impact of BMN 250 on cognitive function in patients with MPS IIIB as assessed by the Development Quotient.

Detailed Summary:
Sponsor: BioMarin Pharmaceutical

Current Primary Outcome:

  • Safety Evaluation of weekly infusions of BMN 250 (Part 1 & Part 2) - Number of participants with abnormal clinical laboratory values and/or Adverse Events that are related to treatment. [ Time Frame: Entire study period, up to 124 weeks ]
    Number of participants with abnormal clinical laboratory values and/or Adverse Events that are related to treatment.
  • Development Quotient (DQ) as efficacy variable with analysis of rate of change of DQ score on treatment vs. rate of change of DQ score prior to treatment. [ Time Frame: Assessed at study end, up to 124 weeks. Collected at: Part 1 - Baseline; Part 2 - Weeks 12, 24, 36, & 48 ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Characterize maximum concentration (Cmax) of BMN 250 in cerebrospinal fluid (CSF) and plasma as relevant through completion of Part 1 and Part 2 [ Time Frame: Study end, up to 124 weeks. Collected at: Pre-dose, 0, 4, 10, 24, 48, 72, 96, 168 hours post-dose for the first dose during each dose escalation in Part 1. Pre-dose, 0, 4, 10, 24, 48, 72, 96, 168 hours post-dose for Baseline, Weeks 5, 12, 36 in Part 2. ]
  • Characterize area under concentration curve (AUC) of BMN 250 in cerebrospinal fluid (CSF) and plasma as relevant through completion of Part 1 and Part 2 [ Time Frame: Study end, up to 124 weeks. Collected at: Pre-dose, 0, 4, 10, 24, 48, 72, 96, 168 hours post-dose for the first dose during each dose escalation in Part 1. Pre-dose, 0, 4, 10, 24, 48, 72, 96, 168 hours post-dose for Baseline, Weeks 5, 12, 36 in Part 2. ]
  • Characterize immunogenicity of BMN 250 total anti-drug anti-body (TAb) in cerebrospinal fluid (CSF) and serum as relevant through completion of Part 1 and Part 2 [ Time Frame: Assessed at study end, up to 124 weeks. Collected at: First dose during each dose escalation in Part 1, and Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 in Part 2 ]
  • Evaluate GAG levels in cerebrospinal fluid (CSF) [ Time Frame: Assessed at study end, up to 124 weeks. Collected at: Each weekly visit as relevant through completion of Part 1 and Part 2 ]
  • Evaluate GAG levels in plasma [ Time Frame: Assessed at study end, up to 124 weeks. Collected at: Each weekly visit as relevant through completion of Part 1 and Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, as relevant in Part 2 ]
  • Evaluate GAG levels in urine [ Time Frame: Assessed at study end, up to 124 weeks. Collected at: Each weekly visit as relevant through completion of Part 1 and Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, as relevant in Part 2 ]
  • Evaluate the impact of BMN 250 treatment on brain structure assessed by magnetic resonance imaging (MRI) [ Time Frame: Assessed at study end, up to 124 weeks. Part 1 - Screening and Baseline; Part 2 - Screening, Baseline, Week 24, and Week 48 ]


Original Secondary Outcome: Same as current

Information By: BioMarin Pharmaceutical

Dates:
Date Received: February 27, 2016
Date Started: April 2016
Date Completion: March 2019
Last Updated: June 22, 2016
Last Verified: May 2016