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

NCT ID: NCT02678689

Last Updated: 2025-02-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-22
• Study Completion Date: 2022-04-20

Brief 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.

Detailed 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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1)

An age-appropriate dose of BMN 190 administered via intracerebroventricular (ICV) infusion every other week (qow) for a duration of 144 weeks.

Group Type: EXPERIMENTAL

BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1)

Intervention Type: BIOLOGICAL

Intracerebroventricular access device

Intervention Type: 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.

Interventions

BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1)

Intervention Type: BIOLOGICAL

Intracerebroventricular 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.

Intervention Type: DEVICE

Other Intervention Names

recombinant human tripeptidyl peptidase-1 (rhTPP1); cerliponase alfa; Brineura®

Eligibility Criteria

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, electroencephalogram (EEG), electrocardiogram (ECG),magnetic resonance imaging (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

• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BioMarin Pharmaceutical

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director, MD

Role: STUDY_DIRECTOR

BioMarin Pharmaceutical

Locations

Nationwide Children's Hospital

Columbus, Ohio, United States

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Children's Hospital Bambino Gesù,IRCCS

Rome, Piazza, Italy

Great Ormond Street Childrens Hospital

London, , United Kingdom

Countries

United States; Germany; Italy; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

190-203

Identifier Type: -

Identifier Source: org_study_id