- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02678689
A Safety, Tolerability, and Efficacy Study of Intracerebroventricular BMN 190 in Pediatric Patients < 18 Years of Age With CLN2 Disease
March 7, 2023 updated by: BioMarin Pharmaceutical
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
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 144 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.
Study Overview
Status
Completed
Conditions
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 help 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 144 weeks.
Study Type
Interventional
Enrollment (Actual)
14
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Hamburg, Germany, 20246
- Universitaetsklinikum Hamburg-Eppendorf
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Piazza
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Rome, Piazza, Italy, 00165
- Children's Hospital Bambino Gesù,IRCCS
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London, United Kingdom, WC1N 3JH
- Great Ormond Street Childrens Hospital
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Ohio
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Columbus, Ohio, United States, 43205
- Nationwide Children's Hospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
1 second to 17 years (Child)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Enrollment over the age of 2 years 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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 144 weeks.
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Other Names:
Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Immunogenicity of BMN 190 in CSF and serum
Time Frame: Up to 144 weeks
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Up to 144 weeks
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Incidence and severity of adverse events as assessed by CTCAE v 4.0
Time Frame: Up to 144 weeks + 6 month follow up post last study treatment
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Up to 144 weeks + 6 month follow up post last study treatment
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Change in the 0-6-point Motor/Language (ML) score on the Hamburg CLN2 rating scale
Time Frame: Up to 144 weeks + 6 month follow up post last study treatment
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Up to 144 weeks + 6 month follow up post last study treatment
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in clinical laboratory tests
Time Frame: Up to 144 weeks
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Up to 144 weeks
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Change in CSF and Plasma laboratory parameters
Time Frame: Up to 144 weeks
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Up to 144 weeks
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Neurological examinations
Time Frame: Up to 144 weeks
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Up to 144 weeks
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Change in Brain Volumes as Assessed by Cranial Magnetic Resonance Imaging (MRI)
Time Frame: Up to 144 weeks
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Up to 144 weeks
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Assess time to disease manifestation for asymptomatic patients
Time Frame: Up to 144 weeks
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Up to 144 weeks
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Change in the total Hamburg CLN2 rating scale
Time Frame: Up to 144 weeks + 6 month follow up post last study treatment
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Up to 144 weeks + 6 month follow up post last study treatment
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Vital signs
Time Frame: Up to 144 weeks + 6 month follow up post last study treatment
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Up to 144 weeks + 6 month follow up post last study treatment
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Physical examination
Time Frame: Up to 144 weeks + 6 month follow up post last study treatment
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Up to 144 weeks + 6 month follow up post last study treatment
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Electrocardiogram (ECG), 3 or 5-lead, 12-lead
Time Frame: Up to 144 weeks + 6 month follow up post last study treatment
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Up to 144 weeks + 6 month follow up post last study treatment
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 1, 2016
Primary Completion (Actual)
April 20, 2022
Study Completion (Actual)
April 20, 2022
Study Registration Dates
First Submitted
January 15, 2016
First Submitted That Met QC Criteria
February 5, 2016
First Posted (Estimate)
February 10, 2016
Study Record Updates
Last Update Posted (Actual)
March 13, 2023
Last Update Submitted That Met QC Criteria
March 7, 2023
Last Verified
March 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 190-203
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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