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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

July 19, 2013
July 24, 2013
February 15, 2018
June 11, 2018
June 11, 2018
September 2013
November 2015   (Final data collection date for primary outcome measure)
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.
number of adverse events [ Time Frame: one year ]
Complete list of historical versions of study NCT01907087 on ClinicalTrials.gov Archive Site
  • 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
  • to evaluate the impact of treatment on measurement of brain atrophy [ Time Frame: change from baseline to after 12 months of treatment with BMN190 ]
  • to characterize single- and repeated-dose PK [ Time Frame: average of 6 periods during the 12 months of treatment with BMN190 ]
  • to determine immunogenicity in CSF and serum [ Time Frame: montly over a period of 12 months ]
Not Provided
Not Provided
 
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
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
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.

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.

Interventional
Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Jansky-Bielschowsky Disease
  • Batten Disease
  • Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2
  • CLN2 Disease
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
Experimental: BMN190
recombinant human tripeptidyl peptidase-1 (rhTPP1/cerliponase alfa)
Intervention: Biological: BMN 190
Schulz A, Ajayi T, Specchio N, de Los Reyes E, Gissen P, Ballon D, Dyke JP, Cahan H, Slasor P, Jacoby D, Kohlschütter A; CLN2 Study Group. Study of Intraventricular Cerliponase Alfa for CLN2 Disease. N Engl J Med. 2018 May 17;378(20):1898-1907. doi: 10.1056/NEJMoa1712649. Epub 2018 Apr 24.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
24
22
November 2015
November 2015   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
3 Years to 15 Years   (Child)
No
Contact information is only displayed when the study is recruiting subjects
Germany,   Italy,   United Kingdom,   United States
 
 
NCT01907087
190-201
Yes
Not Provided
Not Provided
BioMarin Pharmaceutical
BioMarin Pharmaceutical
Not Provided
Study Director: David Jacoby BioMarin Pharmaceutical
BioMarin Pharmaceutical
May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP