Clinical Trial: A Phase 1/2 Open-Label Dose-Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of Intracerebroventricular BMN 190 in Patients With Late-Infantile Neuronal Ceroid Lipofuscinosis (CLN2) Disease

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase 1/2 Open-Label Dose-Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of Intracerebroventricular BMN 190 in Patients With Late-Infantile Neuronal The purpose of this study is to determine whether BMN 190 is safe and effective in the treatment of patients with Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) disease. This is an open label Phase 1/2 study conducted in patients with CLN2 disease. Efficacy measures (disease rating scale and MRI) will be compared to a natural history control.

The study will be conducted under cGCP and patients will be closely monitored.

Sponsor: BioMarin Pharmaceutical

Current Primary Outcome:

• To evaluate the safety of every other week infusions of BMN 190 based on: vital signs, physical examination, electrocardiogram tests, clinical laboratory tests, adverse events, concomitant medications, immunogenicity tests [ Time Frame: 48 weeks ]

  Vital signs, adverse events, concomitant medications: Screening, Baseline, Weeks 1 to 49.

  Physical examination: Screening, Baseline, Weeks 1 to 49.

  Electrocardiogram tests: Baseline, Weeks 1, 24 and 49

  Clinical laboratory tests: Baseline, Weeks 1, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49

  Immunogenicity tests: Baseline, Weeks 1, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49

• To evaluate the efficacy of every other week infusions of BMN 190 by monitoring changes in clinical measures as measured by the CLN2 disease rating scale [ Time Frame: 48 weeks ]
  Screening, baseline, Weeks 1, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49

Original Primary Outcome: number of adverse events [ Time Frame: one year ]

Current Secondary Outcome:

• To evaluate the efficacy of every other week infusions of BMN 190 by monitoring changes in clinical measures as measured by magnetic resonance imaging (MRI) [ Time Frame: 1 year ]
  Screening, Baseline, every 8 weeks during Dose Escalation Period, Weeks 1, 9, 17, 33, 49
• To determine the pharmacokinetic (PK) parameters of infused BMN 190 in subjects with CLN2 [ Time Frame: 48 weeks ]
  Weeks 1, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49

Original Secondary Outcome:

• to evaluate the impact of treatment on measurement of brain atrophy [ Time Frame: change from baseline to after 12 months of treatment with BMN190 ]
• to characterize single- and repeated-dose PK [ Time Frame: average of 6 periods during the 12 months of treatment with BMN190 ]
• to determine immunogenicity in CSF and serum [ Time Frame: montly over a period of 12 months ]

Information By: BioMarin Pharmaceutical

Dates:
Date Received: July 19, 2013
Date Started: September 2013
Date Completion:
Last Updated: April 25, 2016
Last Verified: April 2016