A Safety, Tolerability, and Efficacy Study of Intracerebroventricular BMN 190 in Pediatric Patients < 18 Years of Age With CLN2 Disease

Batten Disease Clinical Trial

Official title:

A Phase 2, Open-Label, Multicenter Study to Evaluate Safety, Tolerability, and Efficacy of Intracerebroventricular BMN 190 in Pediatric Patients < 18 Years of Age With CLN2 Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02678689
• Other study ID #: 190-203
• Status: Completed
• Phase: Phase 2
• Start date: February 2016
• Est. completion date: April 20, 2022

Study information

• Verified date: March 2023
• Source: BioMarin Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This Phase 2 open-label, multicenter study will evaluate the safety, tolerability, and efficacy of BMN 190 intracerebroventricular (ICV) administration every other week (qow) for a period of 144 weeks, in patients with CLN2. The study is designed to assess disease progression in CLN2 patients treated with BMN 190 compared to natural history data from untreated historical controls.

Description:

BMN 190 is a recombinant form of human tripeptidyl peptidase 1 (TPP1), the enzyme deficient in patients with CLN2 diseases (also known as classical late-infantile CLN2, cLINCL, or Jansky-Bielschowsky disease), a form of Batten Disease. As an enzyme replacement therapy (ERT), BMN 190 is designed to help restore TPP1 enzyme activity. BMN 190 is designed to reduce the progressive, pathologic accumulation of lysosomal storage material. 190-203 is a Phase 2 open-label, multicenter study that will evaluate the safety, tolerability, and efficacy of BMN 190 in pediatric patients < 18 years of age with CLN2 disease. Study drug dosing will be determined by the patient's age and administered via intracerebroventricular (ICV) infusion every other week (qow), for a duration of 144 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: April 20, 2022
• Est. primary completion date: April 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 17 Years

Eligibility

Enrollment over the age of 2 years is complete.

Inclusion Criteria:

• Diagnosis of CLN2 disease as determined by TPP1 enzyme activity (dried blood spot) in the fibroblasts and leukocytes available at Screening

• Quantitative clinical assessment of the Hamburg motor-language aggregate score 3-6 at Screening on CLN2 disease motor-language scale, as defined in the Ratings Assessment Guideline

• < 18 years of age at the time of informed consent

• Written informed consent from parent or legal guardian and assent form subject, if appropriate

• Males and females who are of reproductive age should practice true abstinence, defined as no sexual activity, during the study and for 6 months after the study has been completed (or withdrawal from the study). If sexually active and not practicing true abstinence, males and females of reproductive age must use a highly effective method of contraception while participating in the study.

• Ability to comply with protocol required assessments (ICV implantation, drug administration, laboratory sample collection, EEG, ECG, MRI, etc.)

Exclusion Criteria:

• Presence of another inherited neurological disease, e.g., other forms of CLN or seizures unrelated to CLN2 disease (patients with febrile seizures may be eligible)

• Presence of another neurological illness that may have caused cognitive decline (e.g., trauma, meningitis, hemorrhage) or interference with disease rating (autism) before Screening

• Presence of percutaneous feeding tube placement prior to enrollment

• Has received stem cell, gene therapy, or ERT

• Presence of contraindications for neurosurgery (e.g., congenital heart disease, severe respiratory impairment, or clotting abnormalities)

• Presence of contraindications for MRI scans (e.g., cardiac pacemaker, metal fragment or chip in the eye, aneurysm clip in the brain)

• Episode of generalized motor status epilepticus within 4 weeks before the First Dose visit

• Severe infection (e.g., pneumonia, pyelonephritis, or meningitis) within 4 weeks before the First Dose visit (enrollment may be postponed)

• Presence of ventricular abnormality (hydrocephalus, malformation)

• Presence of ventricular shunt

• Has known hypersensitivity to any of the components of BMN 190

• Has received any investigational mediation 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; a female subject judged by the investigator to be of childbearing potential will be tested for pregnancy

Related Conditions & MeSH terms

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

Intervention

Biological:
• BMN190 recombinant human tripeptidyl peptidase-1 (rhTPP1)

Device:
• Intraventricular access device
Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug.

Locations

Country	Name	City	State
Germany	Universitaetsklinikum Hamburg-Eppendorf	Hamburg
Italy	Children's Hospital Bambino Gesù,IRCCS	Rome	Piazza
United Kingdom	Great Ormond Street Childrens Hospital	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	Incidence and severity of adverse events as assessed by CTCAE v 4.0		Up to 144 weeks + 6 month follow up post last study treatment
Primary	Change in the 0-6-point Motor/Language (ML) score on the Hamburg CLN2 rating scale		Up to 144 weeks + 6 month follow up post last study treatment
Primary	Immunogenicity of BMN 190 in CSF and serum		Up to 144 weeks
Secondary	Change in the total Hamburg CLN2 rating scale		Up to 144 weeks + 6 month follow up post last study treatment
Secondary	Change in clinical laboratory tests		Up to 144 weeks
Secondary	Change in CSF and Plasma laboratory parameters		Up to 144 weeks
Secondary	Vital signs		Up to 144 weeks + 6 month follow up post last study treatment
Secondary	Physical examination		Up to 144 weeks + 6 month follow up post last study treatment
Secondary	Neurological examinations		Up to 144 weeks
Secondary	Electrocardiogram (ECG), 3 or 5-lead, 12-lead		Up to 144 weeks + 6 month follow up post last study treatment
Secondary	Change in Brain Volumes as Assessed by Cranial Magnetic Resonance Imaging (MRI)		Up to 144 weeks
Secondary	Assess time to disease manifestation for asymptomatic patients		Up to 144 weeks