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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
Recruitment Status : Completed
First Posted : July 24, 2013
Results First Posted : June 11, 2018
Last Update Posted : June 11, 2018
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical

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

Detailed Description:

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
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


Arm Intervention/treatment
Experimental: BMN190
recombinant human tripeptidyl peptidase-1 (rhTPP1/cerliponase alfa)
Biological: BMN 190
30-300 mg ICV infusion administered every other week for at least 48 weeks.
Other Names:
  • recombinant human tripeptidyl peptidase-1 (rhTPP1)
  • cerliponase alfa




Primary Outcome Measures :
  1. 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 :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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



Information from the National Library of Medicine

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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     History of Changes
Other Study ID Numbers: 190-201
First Posted: July 24, 2013    Key Record Dates
Results First Posted: June 11, 2018
Last Update Posted: June 11, 2018
Last Verified: May 2018

Keywords provided by BioMarin Pharmaceutical:
Late infantile Neuronal Ceroid Lipofuscinosis Type 2
LINCL
NCL2
CLN2
Jansky-Bielschowsky disease

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