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

March 6, 2019 updated by: BioMarin Pharmaceutical

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

The purpose of this study is to determine whether BMN 190 is safe and effective in the treatment of patients with Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) disease.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The purpose of this study is to determine whether BMN 190 is safe and effective in the treatment of patients with Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) disease. This is an open label Phase 1/2 study conducted in patients with CLN2 disease. Efficacy measures (disease rating scale and MRI) will be compared to a natural history control.

The study will be conducted under cGCP and patients will be closely monitored.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Hamburg, Germany, 20246
        • University Hamburg-Eppendorf
  • Italy
      • Rome, Italy, 00165
        • Bambino Gesu Children's Hospital
  • United Kingdom
      • London, United Kingdom, SE1 7EH
        • Guy's & St. Thomas NHS Foundation Trust
      • London, United Kingdom, WC1N 3JH
        • Great Ormond Street Hospital for NHS Foundation Trust
  • United States
    • Ohio
      • Columbus, Ohio, United States, 43205
        • Nationwide Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 15 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: BMN190
recombinant human tripeptidyl peptidase-1 (rhTPP1/cerliponase alfa)
Biological: BMN 190
30-300 mg ICV infusion administered every other week for at least 48 weeks.
Other Names:
  • recombinant human tripeptidyl peptidase-1 (rhTPP1)
  • cerliponase alfa

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Motor-Language (ML) Scale Score During 300 mg Dosing Period
Time Frame: Baseline, Week 49/Last Assessment
The progression of ceroid lipofuscinosis (CLN2) disease was assessed using adapted motor and language domains of the Hamburg rating scale (ML scale score). Motor and Language are each 0 - 3 point subscales in which 3 represents best function and 0 represents loss of function. The sum of the motor and language scores (ML score, 0-6 points) was used to evaluate the loss of function.
Baseline, Week 49/Last Assessment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Percentage changes in whole brain volume from the ITT population for the 300 mg dosing period
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 changes in volume of total grey matter from the ITT population for the 300 mg dosing period
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 changes in total white matter volume from the ITT population for the 300 mg dosing period
Baseline, Week 49
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 changes in volume of cerebrospinal fluid from the ITT population for the 300 mg dosing period
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 changes in whole brain apparent diffusion coefficient from the ITT population for the 300 mg dosing period
Baseline, Week 49

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

BioMarin Pharmaceutical

Investigators

  • Study Director: David Jacoby, BioMarin Pharmaceutical

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2013

Primary Completion (Actual)

November 1, 2015

Study Completion (Actual)

November 1, 2015

Study Registration Dates

First Submitted

July 19, 2013

First Submitted That Met QC Criteria

July 22, 2013

First Posted (Estimate)

July 24, 2013

Study Record Updates

Last Update Posted (Actual)

March 8, 2019

Last Update Submitted That Met QC Criteria

March 6, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 190-201

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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