Clinical Trial: A Safety, Tolerability, and Efficacy Study of Intracerebroventricular BMN 190 in Pediatric Patients < 18 Years of Age With CLN2 Disease

Study Status: Enrolling by invitation
Recruit Status: Enrolling by invitation
Study Type: Interventional

Official Title: A Phase 2, Open-Label, Multicenter Study to Evaluate Safety, Tolerability, and Efficacy of Intracerebroventricular BMN 190 in Pediatric Patients < 18 Years of Age With CLN2 Disease

Brief Summary: This Phase 2 open-label, multicenter study will evaluate the safety, tolerability, and efficacy of BMN 190 intracerebroventricular (ICV) administration every other week (qow) for a period of 96 weeks, in patients with CLN2. The study is designed to assess disease progression in CLN2 patients treated with BMN 190 compared to natural history data from untreated historical controls.

Detailed Summary: BMN 190 is a recombinant form of human tripeptidyl peptidase 1 (TPP1), the enzyme deficient in patients with CLN2 diseases (also known as classical late-infantile CLN2, cLINCL, or Jansky-Bielschowsky disease), a form of Batten Disease. As an enzyme replacement therapy (ERT), BMN 190 is designed to restore TPP1 enzyme activity. BMN 190 is designed to reduce the progressive, pathologic accumulation of lysosomal storage material. 190-203 is a Phase 2 open-label, multicenter study that will evaluate the safety, tolerability, and efficacy of BMN 190 in pediatric patients < 18 years of age with CLN2 disease. Study drug dosing will be determined by the patient's age and administered via intracerebroventricular (ICV) infusion every other week (qow), for a duration of 96 weeks.
Sponsor: BioMarin Pharmaceutical

Current Primary Outcome:

  • Incidence and severity of adverse events as assessed by CTCAE v 4.0 [ Time Frame: Up to 96 weeks ]
  • Change in the 0-6-point Motor/Language (ML) score on the Hamburg CLN2 rating scale [ Time Frame: Up to 96 weeks ]
  • Immunogenicity of BMN 190 in CSF and serum [ Time Frame: Up to 96 weeks ]


Original Primary Outcome:

  • Incidence and severity of adverse events as assessed by CTCAE v 4.0 [ Time Frame: Up to 96 weeks ]
  • Change in CLN2 disease rating score [ Time Frame: Up to 96 weeks ]


Current Secondary Outcome:

  • Change in the total Hamburg CLN2 rating scale [ Time Frame: Up to 96 weeks ]
  • Change in clinical laboratory tests [ Time Frame: Up to 96 weeks ]
  • Change in CSF laboratory parameters [ Time Frame: Up to 96 weeks ]
  • Vital signs [ Time Frame: Up to 96 weeks ]
  • Physical examination [ Time Frame: Up to 96 weeks ]
  • Neurological examinations [ Time Frame: Up to 96 weeks ]
  • 12-Lead electrocardiogram (ECG) [ Time Frame: Up to 96 weeks ]
  • Change in Brain Volumes as Assessed by Cranial Magnetic Resonance Imaging (MRI) [ Time Frame: Up to 96 weeks ]
  • Incidence of and change in abnormalities in standard awake Electroencephalogram (EEG) [ Time Frame: Up to 96 weeks ]
  • Assess time to disease manifestation for asymptomatic patients [ Time Frame: Up to 96 weeks ]


Original Secondary Outcome:

  • Change in the total Hamburg clinical rating scale [ Time Frame: Up to 96 weeks ]
  • Change in clinical laboratory tests [ Time Frame: Up to 96 weeks ]
  • Change in CSF laboratory parameters [ Time Frame: Up to 96 weeks ]
  • Vital signs [ Time Frame: Up to 96 weeks ]
  • Physical examination [ Time Frame: Up to 96 weeks ]
  • Neurological examinations [ Time Frame: Up to 96 weeks ]
  • 12-Lead electrocardiogram (ECG) [ Time Frame: Up to 96 weeks ]
  • Change in Brain Volumes as Assessed by Cranial Magnetic Resonance Imaging (MRI) [ Time Frame: Up to 96 weeks ]
  • Incidence of and change in abnormalities in standard awake Electroencephalogram (EEG) [ Time Frame: Up to 96 weeks ]
  • Immunogenicity laboratory tests [ Time Frame: Up to 96 weeks ]


Information By: BioMarin Pharmaceutical

Dates:
Date Received: January 15, 2016
Date Started: February 2016
Date Completion: December 2022
Last Updated: May 12, 2017
Last Verified: May 2017