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

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ClinicalTrials.gov Identifier: NCT02678689
Recruitment Status : Enrolling by invitation
First Posted : February 10, 2016
Last Update Posted : November 21, 2017
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical

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.

Condition or disease Intervention/treatment Phase
Jansky-Bielschowsky Disease Batten Disease Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2 CLN2 Disease CLN2 Disorder Biological: BMN190 recombinant human tripeptidyl peptidase-1 (rhTPP1) Device: Intraventricular access device Phase 2

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. 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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 2016
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : January 2023


Arm Intervention/treatment
Experimental: BMN190 recombinant human tripeptidyl peptidase-1 (rhTPP1)
An age-appropriate dose of BMN 190 administered via intracerebroventricular (ICV) infusion every other week (qow) for a duration of 96 weeks.
Biological: BMN190 recombinant human tripeptidyl peptidase-1 (rhTPP1)
Other Names:
  • recombinant human tripeptidyl peptidase-1 (rhTPP1)
  • cerliponase alfa
Device: Intraventricular access device
Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug.



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

Secondary Outcome Measures :
  1. Change in the total Hamburg CLN2 rating scale [ Time Frame: Up to 96 weeks ]
  2. Change in clinical laboratory tests [ Time Frame: Up to 96 weeks ]
  3. Change in CSF laboratory parameters [ Time Frame: Up to 96 weeks ]
  4. Vital signs [ Time Frame: Up to 96 weeks ]
  5. Physical examination [ Time Frame: Up to 96 weeks ]
  6. Neurological examinations [ Time Frame: Up to 96 weeks ]
  7. Electrocardiogram (ECG), 3 or 5-lead, 12-lead [ Time Frame: Up to 96 weeks ]
  8. Change in Brain Volumes as Assessed by Cranial Magnetic Resonance Imaging (MRI) [ Time Frame: Up to 96 weeks ]
  9. Incidence of and change in abnormalities in standard awake Electroencephalogram (EEG) [ Time Frame: Up to 96 weeks ]
  10. Assess time to disease manifestation for asymptomatic patients [ Time Frame: Up to 96 weeks ]

Other Outcome Measures:
  1. Abnormal involuntary movements as assessed by the "myoclonus" subscale of the Wiell Cornell Scale [ Time Frame: Up to 96 weeks ]
  2. Retinal anatomy by optical coherence tomography (OCT) [ Time Frame: Up to 96 weeks ]
  3. Seizure onset, type, frequency, and change in seizure activity, as assessed by mUBDRS-Seizure and/or CLN2 Seizure score [ Time Frame: Up to 96 weeks ]
  4. Quality of life as assessed by the PedsQL™ Generic Core Scales [ Time Frame: Up to 96 weeks ]
  5. Quality of life as assessed by the EuroQol Health Status EQ-5D-5L Instrument [ Time Frame: Up to 96 weeks ]
  6. Quality of life as assessed by CLN-2 Specific supplement to the PedsQL [ Time Frame: Up to 96 weeks ]
  7. Analysis of disease-related biomarkers from CSF and blood [ Time Frame: Up to 96 weeks ]
  8. Anti-epileptic treatment [ Time Frame: Up to 96 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Enrollment over the age of 2 is complete.

Inclusion Criteria:

  • Diagnosis of CLN2 disease as determined by TPP1 enzyme activity (dried blood spot) in the fibroblasts and leukocytes available at Screening
  • 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
  • < 18 years of age at the time of informed consent
  • Written informed consent from parent or legal guardian and assent form subject, if appropriate
  • Males and females who are of reproductive age should practice true abstinence, defined as no sexual activity, during the study and for 6 months after the study has been completed (or withdrawal from the study). If sexually active and not practicing true abstinence, males and females of reproductive age must use a highly effective method of contraception while participating in the study.
  • Ability to comply with protocol required assessments (ICV implantation, drug administration, 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 prior to enrollment
  • Has received stem cell, gene therapy, or ERT
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02678689


Locations
United States, Ohio
Columbus, Ohio, United States
Germany
Hamburg, Germany
Italy
Rome, Italy
Sponsors and Collaborators
BioMarin Pharmaceutical
Investigators
Study Director: Temitayo Ajayi, MD BioMarin Pharmaceuticals In.c

Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT02678689     History of Changes
Other Study ID Numbers: 190-203
First Posted: February 10, 2016    Key Record Dates
Last Update Posted: November 21, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No

Additional relevant MeSH terms:
Neuronal Ceroid-Lipofuscinoses
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Lipidoses
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Lipid Metabolism Disorders
Metabolic Diseases