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

Batten Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01907087
• Other study ID #: 190-201
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 2013
• Est. completion date: November 2015

Study information

• Verified date: March 2019
• Source: BioMarin Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 15 Years

Eligibility

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

Related Conditions & MeSH terms

• Batten Disease
• CLN2 Disease
• Jansky-Bielschowsky Disease
• Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2
• Neuronal Ceroid-Lipofuscinoses

Intervention

Biological:
• BMN 190
30-300 mg ICV infusion administered every other week for at least 48 weeks.

Locations

Country	Name	City	State
Germany	University Hamburg-Eppendorf	Hamburg
Italy	Bambino Gesù Children's Hospital	Rome
United Kingdom	Great Ormond Street Hospital for NHS Foundation Trust	London
United Kingdom	Guy's & St. Thomas NHS Foundation Trust	London
United States	Nationwide Children's Hospital	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
BioMarin Pharmaceutical

Countries where clinical trial is conducted

United States,  Germany,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Motor-Language (ML) Scale Score During 300 mg Dosing Period	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.	Baseline, Week 49/Last Assessment
Secondary	Percentage Change From Baseline of Magnetic Resonance Imaging (MRI) at Week 49 During 300 mg Dosing Period: Whole Brain Volume	Percentage changes in whole brain volume from the ITT population for the 300 mg dosing period	Baseline, Week 49
Secondary	Percentage Change From Baseline of Magnetic Resonance Imaging (MRI) at Week 49 During 300 mg Dosing Period: Volume of Total Grey Matter	Percentage changes in volume of total grey matter from the ITT population for the 300 mg dosing period	Baseline, Week 49
Secondary	Percentage Change From Baseline of Magnetic Resonance Imaging (MRI) at Week 49 During 300 mg Dosing Period: Total White Matter Volume	Percentage changes in total white matter volume from the ITT population for the 300 mg dosing period	Baseline, Week 49
Secondary	Percentage Change From Baseline of Magnetic Resonance Imaging (MRI) at Week 49 During 300 mg Dosing Period: Volume of Cerebrospinal Fluid	Percentage changes in volume of cerebrospinal fluid from the ITT population for the 300 mg dosing period	Baseline, Week 49
Secondary	Percentage Change From Baseline of Magnetic Resonance Imaging (MRI) at Week 49 During 300 mg Dosing Period: Whole Brain Apparent Diffusion Coefficient	Percentage changes in whole brain apparent diffusion coefficient from the ITT population for the 300 mg dosing period	Baseline, Week 49