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

BioMarin Pharmaceutical

Status and phase

Completed

Phase 2

Conditions

CLN2 Disease

Jansky-Bielschowsky Disease

CLN2 Disorder

Batten Disease

Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2

Treatments

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

Device: Intraventricular access device

Study type

Interventional

Funder types

Industry

Identifiers

NCT02678689

190-203

Details and patient eligibility

About

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.

Full 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.

Enrollment

14 patients

Sex

All

Ages

Under 17 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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