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
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| ClinicalTrials.gov Identifier: NCT01907087 |
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Recruitment Status :
Completed
First Posted : July 24, 2013
Results First Posted : June 11, 2018
Last Update Posted : March 8, 2019
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Sponsor:
BioMarin Pharmaceutical
Information provided by (Responsible Party):
BioMarin Pharmaceutical
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Brief Summary:
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Jansky-Bielschowsky Disease Batten Disease Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2 CLN2 Disease | Biological: BMN 190 | Phase 1 Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 24 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 Ceroid Lipofuscinosis Type 2 (CLN2) Disease |
| Study Start Date : | September 2013 |
| Actual Primary Completion Date : | November 2015 |
| Actual Study Completion Date : | November 2015 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
CLN5 disease
CLN8 disease
CLN1 disease
CLN7 disease
CLN10 disease
CLN3 disease
CLN6 disease
CLN2 disease
CLN4 disease
| Arm | Intervention/treatment |
|---|---|
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Experimental: BMN190
recombinant human tripeptidyl peptidase-1 (rhTPP1/cerliponase alfa)
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Biological: BMN 190
30-300 mg ICV infusion administered every other week for at least 48 weeks.
Other Names:
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Primary Outcome Measures :
- Motor-Language (ML) Scale Score During 300 mg Dosing Period [ Time Frame: Baseline, Week 49/Last Assessment ]The progression of ceroid lipofuscinosis (CLN2) disease was assessed using adapted motor and language domains of the Hamburg rating scale (ML scale score). Motor and Language are each 0 - 3 point subscales in which 3 represents best function and 0 represents loss of function. The sum of the motor and language scores (ML score, 0-6 points) was used to evaluate the loss of function.
Secondary Outcome Measures :
- Percentage Change From Baseline of Magnetic Resonance Imaging (MRI) at Week 49 During 300 mg Dosing Period: Whole Brain Volume [ Time Frame: Baseline, Week 49 ]Percentage changes in whole brain volume from the ITT population for the 300 mg dosing period
- Percentage Change From Baseline of Magnetic Resonance Imaging (MRI) at Week 49 During 300 mg Dosing Period: Volume of Total Grey Matter [ Time Frame: Baseline, Week 49 ]Percentage changes in volume of total grey matter from the ITT population for the 300 mg dosing period
- Percentage Change From Baseline of Magnetic Resonance Imaging (MRI) at Week 49 During 300 mg Dosing Period: Total White Matter Volume [ Time Frame: Baseline, Week 49 ]Percentage changes in total white matter volume from the ITT population for the 300 mg dosing period
- Percentage Change From Baseline of Magnetic Resonance Imaging (MRI) at Week 49 During 300 mg Dosing Period: Volume of Cerebrospinal Fluid [ Time Frame: Baseline, Week 49 ]Percentage changes in volume of cerebrospinal fluid from the ITT population for the 300 mg dosing period
- Percentage Change From Baseline of Magnetic Resonance Imaging (MRI) at Week 49 During 300 mg Dosing Period: Whole Brain Apparent Diffusion Coefficient [ Time Frame: Baseline, Week 49 ]Percentage changes in whole brain apparent diffusion coefficient from the ITT population for the 300 mg dosing period
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| Ages Eligible for Study: | 3 Years to 15 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Has a diagnosis of CLN2 determined by TPP1 enzyme activity (dried blood spot) available at study entry. If no genotype information is available, blood will be collected for CLN2 gene analysis at baseline. In addition, blood for TPP1 enzyme activity (dried blood spot) will be collected at baseline to be analyzed centrally
- Has mild to moderate disease documented by a two-domain score of 3- 6 on motor and language domains of the Hamburg Scale, with a score of at least 1 in each of these two domains
- Written informed consent from parent or legal guardian and assent from subject, if appropriate
- Has the ability to comply with protocol requirements, in the opinion of the investigator
- Seizures are stable in the judgement of the investigator
Exclusion Criteria:
- Is less than 3 years old at enrollment
- Is 16 years old or older at enrollement
- Has another inherited neurologic disease, e.g. other forms of CLN or seizures unrelated to CLN2 (patients with febrile seizures may be eligible)
- Has another neurological illness that may have caused cognitive decline (e.g., trauma, meningitis, hemorrhage) before study entry
- Requires ventilation support, except for noninvasive support at night
- Has received stem cell, gene therapy, or ERT for CLN2
- Has contraindications for neurosurgery (e.g., congenital heart disease, severe respiratory impairment, or clotting abnormalities)
- Has contraindications for MRI scans (e.g., cardiac pacemaker, metal fragment or chip in the eye, aneurysm clip in the brain)
- Has generalized motor status epilepticus within 4 weeks before the First Dose visit, taking care that status epilepticus is on clinical examination and not only electroencephalogram (EEG) (enrollment may be postponed)
- Has severe infection (e.g., pneumonia, pyelonephritis, or meningitis) within 4 weeks before the First Dose visit (enrollment may be postponed)
- Is prone to complications from intraventricular drug administration, including patients with hydrocephalus or ventricular shunts
- Has known hypersensitivity to any of the components of BMN 190
- Has received any investigational medication 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
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): NCT01907087
Locations
| United States, Ohio | |
| Nationwide Children's Hospital | |
| Columbus, Ohio, United States, 43205 | |
| Germany | |
| University Hamburg-Eppendorf | |
| Hamburg, Germany, 20246 | |
| Italy | |
| Bambino Gesù Children's Hospital | |
| Rome, Italy, 00165 | |
| United Kingdom | |
| Guy's & St. Thomas NHS Foundation Trust | |
| London, United Kingdom, SE1 7EH | |
| Great Ormond Street Hospital for NHS Foundation Trust | |
| London, United Kingdom, WC1N 3JH | |
Sponsors and Collaborators
BioMarin Pharmaceutical
Investigators
| Study Director: | David Jacoby | BioMarin Pharmaceutical |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | BioMarin Pharmaceutical |
| ClinicalTrials.gov Identifier: | NCT01907087 |
| Other Study ID Numbers: |
190-201 |
| First Posted: | July 24, 2013 Key Record Dates |
| Results First Posted: | June 11, 2018 |
| Last Update Posted: | March 8, 2019 |
| Last Verified: | March 2019 |
Keywords provided by BioMarin Pharmaceutical:
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Late infantile Neuronal Ceroid Lipofuscinosis Type 2 LINCL NCL2 CLN2 Jansky-Bielschowsky disease |
Additional relevant MeSH terms:
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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 |