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A Safety, Tolerability, and Efficacy Study of Intracerebroventricular BMN 190 in Patients With CLN2 Disease

This study is enrolling participants by invitation only.
Information provided by (Responsible Party):
BioMarin Pharmaceutical Identifier:
First received: January 15, 2016
Last updated: June 29, 2016
Last verified: June 2016
This Phase 2 open-label study will evaluate the safety, tolerability, and efficacy of BMN 190 intracerebroventricular (ICV) administration at 300mg every other week (qow) for a period of 96 weeks, in patients with CLN2. The study is designed to assess disease progression in siblings of children enrolled in the 190-201 study.

Condition Intervention Phase
Jansky-Bielschowsky Disease
Batten Disease
Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2
CLN2 Disease
CLN2 Disorder
Drug: BMN190 recombinant human tripeptidyl peptidase-1 (rhTPP1)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Open-Label Study to Evaluate Safety, Tolerability, and Efficacy of Intracerebroventricular BMN 190 in Patients With CLN2 Disease

Resource links provided by NLM:

Further study details as provided by BioMarin Pharmaceutical:

Primary Outcome Measures:
  • Incidence and severity of adverse events as assessed by CTCAE v 4.0 [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: Yes ]
  • Change in CLN2 disease rating score [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in the total Hamburg clinical rating scale [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: No ]
  • Change in clinical laboratory tests [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: Yes ]
  • Change in CSF laboratory parameters [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: Yes ]
  • Vital signs [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: Yes ]
  • Physical examination [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: Yes ]
  • Neurological examinations [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: Yes ]
  • 12-Lead electrocardiogram (ECG) [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: Yes ]
  • Change in Brain Volumes as Assessed by Cranial Magnetic Resonance Imaging (MRI) [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of and change in abnormalities in standard awake Electroencephalogram (EEG) [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: Yes ]
  • Immunogenicity laboratory tests [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • Abnormal involuntary movements as assessed by the "myoclonus" subscale of the Wiell Cornell Scale [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: No ]
  • Retinal anatomy by optical coherence tomography (OCT) [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: No ]
  • Seizure onset, type and frequency as assessed by mUBDRS-Seizure [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: No ]
  • Quality of life as assessed by the PedsQL™ Generic Core Scales [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: No ]
  • Quality of life as assessed by the EuroQol Health Status EQ-5D-5L Instrument [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: No ]
  • Quality of life as assessed by CLN-2 Specific supplement to the PedsQL [ Time Frame: Up to 96 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 5
Study Start Date: February 2016
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BMN190 recombinant human tripeptidyl peptidase-1 (rhTPP1)
300mg of BMN 190 administered via intracerebroventricular (ICV) infusion every other week (qow) for a duration of 96 weeks.
Drug: BMN190 recombinant human tripeptidyl peptidase-1 (rhTPP1)

Detailed Description:
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, and improve the symptoms of disease. 190-203 is a Phase 2 open-label study that will evaluate the safety, tolerability, and efficacy of BMN 190 in patients with siblings enrolled in the 190-201 study. Study drug administration consists of 300mg dosing administered via intracerebroventricular (ICV) infusion every other week (qow), for a duration of 96 weeks.

Ages Eligible for Study:   1 Year and older   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of CLN2 disease determined by TPP1 enzyme activity available at Screening
  • At least 1 sibling with confirmed CLN2 disease who was enrolled in Study 190-201
  • Quantitative clinical assessment of the Hamburg motor-language aggregate score 3-6 at Screening on CLN2 disease motor-language scale, as defined in the Ratings Assessment Guideline
  • Age ≥ 1 year at the time of informed consent
  • Written informed consent from parent or legal guardian and assent form subject, if appropriate
  • Ability to comply with protocol required assessments (laboratory sample collection, EEG, ECG, MRI, etc.)

Exclusion Criteria:

  • Presence of another inherited neurological disease, e.g., other forms of CLN or seizures unrelated to CLN2 disease (patients with febrile seizures may be eligible)
  • Presence of another neurological illness that may have caused cognitive decline (e.g., trauma, meningitis, hemorrhage) or interference with disease rating (autism) before Screening
  • Presence of percutaneous feeding tube placement
  • Has received stem cell, gene therapy, or ERT for CLN2 disease
  • Presence of contraindications for neurosurgery (e.g., congenital heart disease, severe respiratory impairment, or clotting abnormalities)
  • Presence of contraindications for MRI scans (e.g., cardiac pacemaker, metal fragment or chip in the eye, aneurysm clip in the brain)
  • Episode of generalized motor status epilepticus within 4 weeks before the First Dose visit
  • Severe infection (e.g., pneumonia, pyelonephritis, or meningitis) within 4 weeks before the First Dose visit (enrollment may be postponed)
  • Presence of ventricular abnormality (hydrocephalus, malformation)
  • Presence of ventricular shunt
  • Has known hypersensitivity to any of the components of BMN 190
  • Has received any investigational mediation within 30 days before the first infusion of study drug or is scheduled to receive any investigational drug other than BMN 190 during the course of the study
  • Has a medical condition or extenuating circumstance that, in the opinion of the investigator, might compromise the subject's ability to comply with the protocol required testing or procedures or compromise the subject's well being, safety, or clinical interpretability
  • Pregnancy any time during the study; a female subject judged by the investigator to be of childbearing potential will be tested for pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02678689

United States, Ohio
Columbus, Ohio, United States
Hamburg, Germany
Sponsors and Collaborators
BioMarin Pharmaceutical
Study Director: Temitayo Ajayi, MD BioMarin Pharmaceutical
  More Information

Responsible Party: BioMarin Pharmaceutical Identifier: NCT02678689     History of Changes
Other Study ID Numbers: 190-203 
Study First Received: January 15, 2016
Last Updated: June 29, 2016
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
United States: Food and Drug Administration

Additional relevant MeSH terms:
Neuronal Ceroid-Lipofuscinoses
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Lipid Metabolism Disorders
Metabolic Diseases processed this record on September 30, 2016