Clinical trial NCT02678689: A Safety, Tolerability, and Efficacy Study of BMN 190 in Pediatric Patients < 18 Years of Age With CLN2 Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Jansky-Bielschowsky Disease
Batten Disease
Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2
CLN2 Disease
CLN2 Disorder
Lead sponsor: BioMarin Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2016-02-10
Enrollment: 14
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Motor Language (ML) Scale: Rate of Decline in the 0 to 6-point ML Score.
timeFrame: Baseline to Last assessment (Week 169)
measure: Probability of Unreversed 2-Point Decline in Motor-language (ML) Score or Score of 0
timeFrame: Baseline to Last assessment (Week 169)
measure: Probability of Decline of Unreversed Motor-language (ML) Score of 0
timeFrame: Baseline to Last assessment (Week 169)
measure: Rate of Decline in Individual Motor Domains
timeFrame: Baseline to Last assessment (Week 169)
measure: Rate of Decline in Individual Language Domains
timeFrame: Baseline to Last assessment (Week 169)
Secondary outcomes:
measure: Probability of Decline of Disease Manifestation at Week 49 & 97
timeFrame: Baseline to Last assessment (Week 169)
measure: Probability of Decline of Disease Manifestation at Week 145
timeFrame: Baseline to Week 145
measure: Change From Baseline in ML Scale Score
timeFrame: Baseline to Week 49, Week 97, Week 145, & Week 169
measure: Changes From Baseline in MLV Scale Score
timeFrame: Baseline to Week 49, Week 97, Week 145, & Week 169
measure: Changes From Baseline in the 0-12 Point MLVS Motor, Language, Vision, and Seizure Subscales (MLVS) Score.
timeFrame: Baseline to Week 49, Week 97, Week 145, & Week 169
measure: Percentage Change From Baseline to Last Assessment: Volume of Cerebrospinal Fluid (mL)
timeFrame: Baseline to Last assessment (Week 169)
measure: Percentage Change From Baseline to Last Assessment: Volume of Total Cortical Gray Matter (mL)
timeFrame: Baseline to Last assessment (Week 169)
measure: Percentage Change From Baseline to Last Assessment: Volume of Total White Matter (mL)
timeFrame: Baseline to Last assessment (Week 169)
measure: Change From Baseline to Last Assessment: Whole Brain Apparent Diffusion Coefficient Value
timeFrame: Baseline to Last assessment (Week 169)
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
city: Rome
country: Italy
facility: Children's Hospital Bambino Gesù,IRCCS
state: Piazza
city: London
country: United Kingdom
facility: Great Ormond Street Childrens Hospital
Study officials:
affiliation: BioMarin Pharmaceutical
name: Medical Director, MD
role: STUDY_DIRECTOR
References: