E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neuronal Ceroid Lipofuscinosis type 2 (CLN2) disease |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052074 |
E.1.2 | Term | Neuronal ceroid lipofuscinosis NOS |
E.1.2 | System Organ Class | 100000004850 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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
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E.2.2 | Secondary objectives of the trial |
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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.)
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E.4 | Principal 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
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E.5 End points |
E.5.1 | 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary efficacy endpoint should be measured every 4 weeks during the study. |
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E.5.2 | 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. |
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E.5.2.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
External Control (Historical Control) |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
External Control (Historical Control) |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |