Phase 2 N=43 Treatment

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

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

Bottom Line

View on ClinicalTrials.gov: NCT02678689 ↗

Enrolled (actual)

Serious AEs

85.7%

Results posted

Feb 2025

Primary outcome: Primary: Motor Language (ML) Scale: Rate of Decline in the 0 to 6-point ML Score. — 0.15; 1.30 change in score/48 wk — p=< 0.0001

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) (Biological); Intracerebroventricular access device (Device)
Age: Pediatric
Sex: All
Sponsor: BioMarin Pharmaceutical
Primary completion: Apr 2022

Outcome Measures

Outcome	Result	p-value
PRIMARY Motor Language (ML) Scale: Rate of Decline in the 0 to 6-point ML Score.	0.15; 1.30	< 0.0001 sig
PRIMARY Probability of Unreversed 2-Point Decline in Motor-language (ML) Score or Score of 0	0.0; 0.141; 0.083; 0.397; 0.167; 0.774	<.0001 sig
PRIMARY Probability of Decline of Unreversed Motor-language (ML) Score of 0	0.0; 0.03; 0.0; 0.149; 0.0; 0.336	0.0032 sig
PRIMARY Rate of Decline in Individual Motor Domains	0.05; 0.59	<.0001 sig
PRIMARY Rate of Decline in Individual Language Domains	0.10; 0.77	<.0001 sig
SECONDARY Probability of Decline of Disease Manifestation at Week 49 & 97	0.143; 0.405; 0.286; 0.762	0.0081 sig
SECONDARY Probability of Decline of Disease Manifestation at Week 145	0.429	—
SECONDARY Change From Baseline in ML Scale Score	-0.0; -0.8; 0.0; -1.6; -0.4; -3.1	—
SECONDARY Changes From Baseline in MLV Scale Score	-0.1; -1.0; -0.1; -2.1; -0.7; -3.9	—
SECONDARY Changes From Baseline in the 0-12 Point MLVS Motor, Language, Vision, and Seizure Subscales (MLVS) Score.	-0.2; -1.5; -0.1; -3.0; -0.6; -5.5	—
SECONDARY Percentage Change From Baseline to Last Assessment: Volume of Cerebrospinal Fluid (mL)	0.7	—
SECONDARY Percentage Change From Baseline to Last Assessment: Volume of Total Cortical Gray Matter (mL)	-10.3	—
SECONDARY Percentage Change From Baseline to Last Assessment: Volume of Total White Matter (mL)	5.4	—
SECONDARY Change From Baseline to Last Assessment: Whole Brain Apparent Diffusion Coefficient Value	0.0	—

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.

Eligibility Criteria

Enrollment 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, 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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02678689). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.