Phase 2 study to evaluate safety and efficacy of BMN 190 in patients with CLN2

• Register: EUCTR
• Last refreshed on: 16 October 2017
• Main ID: EUCTR2015-000891-85-DE
• Date of registration: 04/11/2015
• Prospective Registration: Yes
• Primary sponsor: BioMarin Pharmaceutical Inc.
• Public title: Phase 2 study to evaluate safety and efficacy of BMN 190 in patients with CLN2
• Scientific title: A Phase 2 Open-Label Study to Evaluate Safety, Tolerability, and Efficacy of Intracerebroventricular BMN 190 in Pediatric Patients < 18 years of age with CLN2 Disease
• Date of first enrolment: 19/01/2016
• Target sample size: 10
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000891-85
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: External Control (Historical Control) If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: External Control (Historical Control) Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany, Italy, United Kingdom

Contacts

• Name: Clinical Trials Information
• Affiliation: BioMarin Pharmacutical Inc.

• Name: Clinical Trials Information
• Affiliation: BioMarin Pharmacutical Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
• Diagnosis of CLN2 disease as determined by TPP1 enzyme activity (dried blood spot) in the fibroblasts and leukocytes available at Screening. Note: Blood for TPP1 enzyme activity and CLN2 gene analysis must be collected to be analyzed centrally.
• Quantitative clinical assessment of the Hamburg motor-language aggregate score 3-6 at Screening, 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 from 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.)

Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Another inherited neurologic disease, e.g., other forms of CLN or seizures unrelated to CLN2 disease (patients with febrile seizures may be eligible)
• Another neurological illness that may have caused cognitive decline (e.g., trauma, meningitis, hemorrhage) or interfere with disease rating (autism) before Screening
• Percutaneous feeding tube placement prior to enrollment
• Has received stem cell, gene therapy, or ERT
• Contraindications for neurosurgery (e.g., congenital heart disease, severe respiratory impairment, or clotting abnormalities)
• 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 medication 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 wellbeing, 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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Neuronal Ceroid Lipofuscinosis type 2 (CLN2) disease
MedDRA version: 20.0 Level: LLT Classification code 10052074 Term: Neuronal ceroid lipofuscinosis NOS System Organ Class: 100000157084

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: Brineura
Product Name: cerliponase alfa
Product Code: BMN 190
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: cerliponase alfa
CAS Number: 151662-36-1
Current Sponsor code: BMN 190
Other descriptive name: recombinant human tripeptidyl peptidase-1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 30-

Primary Outcome(s)

Secondary Objective: Secondary objectives of this study include the following:
• characterize the PK of BMN 190 in CSF and plasma
• measure MRI parameters of disease progression
• assess impact of treatment on the total Hamburg clinical rating scale
• assess the time to disease manifestation for asymptomatic patients

Primary end point(s): The primary efficacy endpoint is the 0 to 6-point ML score on the Hamburg CLN2 rating scale. The primary measure of efficacy is the rate of CLN2 decline.

Main Objective: The primary objectives of this study include the following:
• evaluate safety and tolerability of BMN 190 administered via intracerebroventricular (ICV) device
• evaluate treatment effectiveness as a delay in progression of motor-language (ML) score on the Hamburg CLN2 clinical rating scale
• assess immunogenicity of BMN 190 in CSF and serum

Timepoint(s) of evaluation of this end point: The primary efficacy endpoint should be measured every 4 weeks during the study.

Secondary Outcome(s)

Secondary end point(s): Secondary endpoints of key interest include measurements obtained from MRI of the brain, time to disease manifestation (asymptomatic patients), time to first confirmed CLN2 decline (all patients), and the 0 to 12-point total (motor/language/vision/seizure) Hamburg CLN2 scores.

Timepoint(s) of evaluation of this end point: MRI of the brain should be performed every 24 weeks. The 0 to 12-point total (motor/language/vision/seizure) Hamburg CLN2 scores should be measured every 4 weeks.

Secondary ID(s)

190-203

Source(s) of Monetary Support

BioMarin Pharmaceutical Inc.