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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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01907087
First Posted: July 24, 2013
Last Update Posted: April 27, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
BioMarin Pharmaceutical
  Purpose
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 Intervention Phase
Jansky-Bielschowsky Disease Batten Disease Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2 CLN2 Disease Biological: BMN 190 Phase 1 Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by BioMarin Pharmaceutical:

Primary Outcome Measures:
  • To evaluate the safety of every other week infusions of BMN 190 based on: vital signs, physical examination, electrocardiogram tests, clinical laboratory tests, adverse events, concomitant medications, immunogenicity tests [ Time Frame: 48 weeks ]

    Vital signs, adverse events, concomitant medications: Screening, Baseline, Weeks 1 to 49.

    Physical examination: Screening, Baseline, Weeks 1 to 49.

    Electrocardiogram tests: Baseline, Weeks 1, 24 and 49

    Clinical laboratory tests: Baseline, Weeks 1, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49

    Immunogenicity tests: Baseline, Weeks 1, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49


  • To evaluate the efficacy of every other week infusions of BMN 190 by monitoring changes in clinical measures as measured by the CLN2 disease rating scale [ Time Frame: 48 weeks ]
    Screening, baseline, Weeks 1, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49


Secondary Outcome Measures:
  • To evaluate the efficacy of every other week infusions of BMN 190 by monitoring changes in clinical measures as measured by magnetic resonance imaging (MRI) [ Time Frame: 1 year ]
    Screening, Baseline, every 8 weeks during Dose Escalation Period, Weeks 1, 9, 17, 33, 49

  • To determine the pharmacokinetic (PK) parameters of infused BMN 190 in subjects with CLN2 [ Time Frame: 48 weeks ]
    Weeks 1, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49


Enrollment: 24
Study Start Date: September 2013
Study Completion Date: March 2016
Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 16 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 requirements or compromise the subject's well being, safety, or clinical interpretability
  • 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
  Contacts and Locations
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
Great Ormand Street Hospital For Children
London, United Kingdom
Sponsors and Collaborators
BioMarin Pharmaceutical
Investigators
Study Director: David Jacoby BioMarin Pharmaceutical
  More Information

Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT01907087     History of Changes
Other Study ID Numbers: 190-201
First Submitted: July 19, 2013
First Posted: July 24, 2013
Last Update Posted: April 27, 2016
Last Verified: April 2016

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