A Phase 1/2 Open-Label Dose-Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of Intracerebroventricular BMN 190 in Patients With Late-Infantile Neuronal Ceroid Lipofuscinosis (CLN2) Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01907087
• Date of registration: 19/07/2013
• Prospective Registration: Yes
• Primary sponsor: BioMarin Pharmaceutical
• Public title: A Phase 1/2 Open-Label Dose-Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of Intracerebroventricular BMN 190 in Patients With Late-Infantile Neuronal Ceroid Lipofuscinosis (CLN2) Disease
• Scientific title: A Phase 1/2 Open-Label Dose-Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of Intracerebroventricular BMN 190 in Patients With Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) Disease
• Date of first enrolment: September 2013
• Target sample size: 24
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01907087
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Germany, Italy, United Kingdom, United States

Contacts

• Name: David Jacoby
• Affiliation: BioMarin Pharmaceutical

Key inclusion & exclusion criteria

Inclusion Criteria:

- Has a diagnosis of CLN2 determined by TPP1 enzyme activity (dried blood spot)
available at study entry. If no genotype information is available, blood will be
collected for CLN2 gene analysis at baseline. In addition, blood for TPP1 enzyme
activity (dried blood spot) will be collected at baseline to be analyzed centrally

- Has mild to moderate disease documented by a two-domain score of 3- 6 on motor and
language domains of the Hamburg Scale, with a score of at least 1 in each of these two
domains

- Written informed consent from parent or legal guardian and assent from subject, if
appropriate

- Has the ability to comply with protocol requirements, in the opinion of the
investigator

- Seizures are stable in the judgement of the investigator

Exclusion Criteria:

- Is less than 3 years old at enrollment

- Is 16 years old or older at enrollement

- Has another inherited neurologic disease, e.g. other forms of CLN or seizures
unrelated to CLN2 (patients with febrile seizures may be eligible)

- Has another neurological illness that may have caused cognitive decline (e.g., trauma,
meningitis, hemorrhage) before study entry

- Requires ventilation support, except for noninvasive support at night

- Has received stem cell, gene therapy, or ERT for CLN2

- Has contraindications for neurosurgery (e.g., congenital heart disease, severe
respiratory impairment, or clotting abnormalities)

- Has contraindications for MRI scans (e.g., cardiac pacemaker, metal fragment or chip
in the eye, aneurysm clip in the brain)

- Has generalized motor status epilepticus within 4 weeks before the First Dose visit,
taking care that status epilepticus is on clinical examination and not only
electroencephalogram (EEG) (enrollment may be postponed)

- Has severe infection (e.g., pneumonia, pyelonephritis, or meningitis) within 4 weeks
before the First Dose visit (enrollment may be postponed)

- Is prone to complications from intraventricular drug administration, including
patients with hydrocephalus or ventricular shunts

- 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 well being, safety, or
clinical interpretability

- Pregnancy any time during the study



Age minimum: 3 Years
Age maximum: 15 Years
Gender: All

Health Condition(s) or Problem(s) studied

Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2

Jansky-Bielschowsky Disease

CLN2 Disease

Batten Disease

Intervention(s)

Biological: BMN 190

Primary Outcome(s)

Motor-Language (ML) Scale Score During 300 mg Dosing Period [Time Frame: Baseline, Week 49/Last Assessment]

Secondary Outcome(s)

Percentage Change From Baseline of Magnetic Resonance Imaging (MRI) at Week 49 During 300 mg Dosing Period: Volume of Cerebrospinal Fluid [Time Frame: Baseline, Week 49]

Percentage Change From Baseline of Magnetic Resonance Imaging (MRI) at Week 49 During 300 mg Dosing Period: Total White Matter Volume [Time Frame: Baseline, Week 49]

Percentage Change From Baseline of Magnetic Resonance Imaging (MRI) at Week 49 During 300 mg Dosing Period: Whole Brain Apparent Diffusion Coefficient [Time Frame: Baseline, Week 49]

Percentage Change From Baseline of Magnetic Resonance Imaging (MRI) at Week 49 During 300 mg Dosing Period: Volume of Total Grey Matter [Time Frame: Baseline, Week 49]

Percentage Change From Baseline of Magnetic Resonance Imaging (MRI) at Week 49 During 300 mg Dosing Period: Whole Brain Volume [Time Frame: Baseline, Week 49]

Secondary ID(s)

190-201

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 11/06/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01907087