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

NCT02678689 | Completed Phase 2 Results DMC FDA Drug FDA Device

• 1 other identifier: 190-203
• Study Type: interventional
• Target: 14
• Locations: 4 countries
• Sites: 4

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.

Conditions

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

Outcome Measures

Primary Outcomes (5)

• Motor Language (ML) Scale: Rate of Decline in the 0 to 6-point ML Score.

  Rate of decline in 0 to 6-point ML score, \& primary analysis was based on up to 3-1 matching of Study 190-901 evaluable participants with Study 190-203 ITT participants. Rate of decline =(-1)x(48x7)x(Ending score - Starting score)/(Ending date - Starting date) A positive rate of decline means that subject declined, a negative rate of decline means that subject improved. The combined motor/gait and language (ML) score, as derived from Hamburg CLN2 rating scale, immediately preceding first infusion. The combined ML score is determined as sum of 0-3 point motor(M) \& language(L) subscales where 0 represents no function, \& 3 represents normal function, \& can range from 0(severely impaired) to 6(normal). Thus,high scores describe better function \& low scores describe poor function. The starting assessment is baseline ML assessment \& ending assessment is last ML score \>0. Note for Study 190-901, baseline ML assessment is defined as assessment of matching to Study 190-203 subj.

  Baseline to Last assessment (Week 169)

• Probability of Unreversed 2-Point Decline in Motor-language (ML) Score or Score of 0

  An unreversed 2-point decline is any decline of 2 points or more that had not reversed to a 1-point decline (or better) at last recorded observation. An unreversed score of 0 is a decline to 0 that had not increased to a score \>0 at last recorded observation ML score decline is measured by motor \& language domains on CLN2 rating scale. Combined motor/gait \&language (ML) score, as derived from Hamburg CLN2 rating scale, immediately preceding first infusion. Combined ML score is determined as sum of the 0-3 point motor(M)\&language(L) where 0 represents no function, \& 3 represents normal function, \& can range from 0 (severely impaired) to 6 (normal). Thus, high scores describe better function \& low scores describe poor function Model includes data up to week 169. Estimates from the model are presented for Wks 49, 97 \& 145 No.analyzed is no.of subj out of overall no.of participants analyzed who have not been censored/had unreversed 2-point decline/score of 0 at given time points.

  Baseline to Last assessment (Week 169)

• Probability of Decline of Unreversed Motor-language (ML) Score of 0

  The combined motor/gait and language (ML) score, as derived from the Hamburg CLN2 rating scale, immediately preceding the first infusion. The combined ML score is determined as the sum of the 0-3 point motor (M) and language (L) subscales where 0 represents no function, and 3 represents normal function, and can range from 0 (severely impaired) to 6 (normal). Thus, high scores describe better function and low scores describe poor function. Model includes data up to week 169. Estimates from the model are presented for Weeks 49, 97 and 145. No.analyzed is no.of subj out of overall no.of participants analyzed who have not been censored/had unreversed decline/score of 0 at given time points

  Baseline to Last assessment (Week 169)

• Rate of Decline in Individual Motor Domains

  Rate of decline = (-1) x (48 x 7) x (Ending score - Starting score)/(Ending date - Starting date). A positive rate of decline means that the subject declined, a negative rate of decline means that the subject improved. The 0-3 point motor (M) subscales, as derived from the Hamburg CLN2 rating scale, where 0 represents no function, and 3 represents normal function. Thus, high scores describe better function, and low scores describe poor function.

  Baseline to Last assessment (Week 169)

• Rate of Decline in Individual Language Domains

  Rate of decline = (-1) x (48 x 7) x (Ending score - Starting score)/(Ending date - Starting date). A positive rate of decline means that the subject declined, a negative rate of decline means that the subject improved. The 0-3 point language (L) subscales, as derived from the Hamburg CLN2 rating scale, where 0 represents no function, and 3 represents normal function. Thus, high scores describe better function and low scores describe poor function. Patients with baseline score of 0 are excluded.

  Baseline to Last assessment (Week 169)

Secondary Outcomes (9)

• Probability of Decline of Disease Manifestation at Week 49 & 97

  Baseline to Last assessment (Week 169)

• Probability of Decline of Disease Manifestation at Week 145

  Baseline to Week 145

• Change From Baseline in ML Scale Score

  Baseline to Week 49, Week 97, Week 145, & Week 169

• Changes From Baseline in MLV Scale Score

  Baseline to Week 49, Week 97, Week 145, & Week 169

• Changes From Baseline in the 0-12 Point MLVS Motor, Language, Vision, and Seizure Subscales (MLVS) Score.

  Baseline to Week 49, Week 97, Week 145, & Week 169

Study Arms (1)

BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1)

EXPERIMENTAL

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

Biological: BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1); Device: Intracerebroventricular access device

Interventions

BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1) BIOLOGICAL

Also known as: recombinant human tripeptidyl peptidase-1 (rhTPP1), cerliponase alfa, Brineura®

BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1)

Intracerebroventricular access device 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.

BMN 190 recombinant human tripeptidyl peptidase-1 (rhTPP1)

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.)

You may not qualify if:

• 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

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (4)

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Children's Hospital Bambino Gesù,IRCCS

Rome, Piazza, 00165, Italy

Location

Great Ormond Street Childrens Hospital

London, WC1N 3JH, United Kingdom

Location

MeSH Terms

Conditions

Neuronal Ceroid-Lipofuscinoses

Interventions

cerliponase alfa

Condition Hierarchy (Ancestors)

Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Pascal Reisewitz, Global Medical Director, PhD
• Organization: BioMarin Pharmaceutical Inc

medinfo@bmrn.com

1-800-983-4587

Study Officials

• Medical Director, MD

  BioMarin Pharmaceutical

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2016
• First Posted: February 10, 2016
• Study Start: January 22, 2016
• Primary Completion: April 20, 2022
• Study Completion: April 20, 2022
• Last Updated: February 17, 2025
• Results First Posted: February 17, 2025

Record last verified: 2024-11

Locations

US (1); IT (1); DE (1); GB (1)