An Extension Study to Evaluate the Long-Term Efficacy and Safety of BMN 190 in Patients With CLN2 Disease

Batten Disease Clinical Trial

Official title:

A Multicenter, Multinational, Extension Study to Evaluate the Long-Term Efficacy and Safety of BMN 190 in Patients With CLN2 Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02485899
• Other study ID #: 190-202
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 2015
• Est. completion date: December 10, 2020

Study information

• Verified date: July 2022
• Source: BioMarin Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The Phase 1/2 study (190-201) evaluated the efficacy and safety of a 300 mg dose of BMN 190 administered every other week (qow) to patients with CLN2. The dose and regimen for this study (190-202) are based on the results of the 190-201 study. The rationale for this phase 2 extension study is to provide patients who complete the 190-201 study with the option to continue BMN 190 treatment. The 190-202 study is an open label extension protocol to assess long-term safety and efficacy.

Description:

BMN 190 is a recombinant form of human tripeptidyl peptidase 1 (TPP1), the enzyme deficient in patients with CLN2 disease (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. The Phase 1/2 study (190-201) evaluated the efficacy and safety of a 300 mg dose of BMN 190 administered every other week (qow) to patients with CLN2. The dose and regimen for this study (190-202) are based on the results of the 190-201 study. The rationale for this phase 2 extension study is to provide patients who complete the 190-201 study with the option to continue BMN 190 treatment. The 190-202 study is an open label extension protocol to assess long-term safety and efficacy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: December 10, 2020
• Est. primary completion date: December 10, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 16 Years

Eligibility

Inclusion Criteria:

• Must have completed 48 weeks in Study 190-201.

• Is willing and able to provide written, signed informed consent. Or, in the case of patients under the age of 18 (or other age as defined by regional law or regulation), provide written assent (if required) and have written informed consent, signed by a legally authorized representative, after the nature of the study has been explained, and prior to performance of research-related procedures.

• 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.

• If female, of childbearing potential, must have a negative pregnancy test at the Screening Visit and be willing to have additional pregnancy tests done during the study.

Exclusion Criteria:

• Has had a loss of 3 or more points in the combined motor and language components of the Hamburg CLN2 rating scale between Baseline of Study 190-201 and the Study Completion visit in Study 190-201 and would not benefit from enrolling in the study in the Investigator's discretion.

• Has a score of 0 points on the combined motor and language components of the Hamburg CLN2 rating scale.

• Is pregnant or breastfeeding, at Baseline, or planning to become pregnant (self or partner) at any time during the study.

• Has used any investigational product (other than BMN 190 in 190-201), or investigational medical device, within 30 days prior to Baseline; or is required to use any investigational agent prior to completion of all scheduled study assessments.

• Has a concurrent disease or condition that would interfere with study participation, or pose a safety risk, as determined by the Investigator.

• Has any condition that, in the view of the Investigator, places the patient at high risk of poor treatment compliance or of not completing the study.

Related Conditions & MeSH terms

• Batten Disease
• CLN2 Disease
• CLN2 Disorder
• Jansky-Bielschowsky Disease
• Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2
• Neuronal Ceroid-Lipofuscinoses

Intervention

Biological:
• BMN 190
300 mg Intracerebroventricular (ICV) infusion administered every other week for up to 240 weeks

Device:
• Intracerebroventricular (ICV) access device
Surgical implantation of an MRI compatible ICV access device in the lateral ventricle of the right hemisphere is required for administration of study drug.

Locations

Country	Name	City	State
Germany	Universitaetsklinikum Hamburg-Eppendorf	Hamburg
Italy	Children's Hospital Bambino Gesù,IRCCS	Rome	Piazza
United Kingdom	Great Ormond Street Childrens Hospital	London
United States	Nationwide Children's Hospital	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
BioMarin Pharmaceutical

Countries where clinical trial is conducted

United States,  Germany,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Probability of Unreversed 2-point Decline in Motor-language (ML) Score or Score of 0	Motor and Language are each 0-3 point subscales in which 3 represents best function and 0 represents loss of function. Thus, the 0-6 point ML score was used as the primary mode of evaluation of loss of function.; In 190-201, the primary endpoint was a responder endpoint: unreversed ML 2-point decline or score of 0 at Week 48 compared to the 50% rate expected in natural history using the 1-sample binomial test. For 190-202, the primary endpoint was revised to assess response over the full duration of follow-up. It is not clear, given the variable follow-up much greater than 48 weeks, what response rate is expected in natural history. For this reason, the assessment of the primary endpoint is based on comparing to natural history data and using the Kaplan-Meier method and Cox proportional hazards model with covariate adjustment (i.e., baseline ML score and age as continuous covariates, and genotype [common alleles] and sex as categorical covariates).	Up to Week 289
Primary	Probability of Unreversed Motor-language (ML) Score of Zero.	Motor and Language are each 0-3 point subscales in which 3 represents best function and 0 represents loss of function. Thus, the 0-6 point ML score was used as the primary mode of evaluation of loss of function.; In 190-201, the primary endpoint was a responder endpoint: unreversed ML 2-point decline or score of 0 at Week 48 compared to the 50% rate expected in natural history using the 1-sample binomial test. For 190-202, the primary endpoint was revised to assess response over the full duration of follow-up. It is not clear, given the variable follow-up much greater than 48 weeks, what response rate is expected in natural history. For this reason, the assessment of the primary endpoint is based on comparing to natural history data and using the Kaplan-Meier method and Cox proportional hazards model with covariate adjustment (baseline ML score, age, genotype [common alleles], and sex).	Up to Week 289
Secondary	Whole Brain Volume	Percentage change from Baseline to Last Observation: Whole Brain volume	Baseline (Week 1 of BMN 190-201) to Week 289 / Last observation
Secondary	Volume of Cerebrospinal Fluid	Percentage Change from Baseline to last observation: Volume of cerebrospinal fluid	Baseline (Week 1 of BMN 190-201) to Week 289 / Last observation
Secondary	Volume of Total Cortical Gray Matter	Percentage Change from Baseline to last observation: Volume of total cortical gray matter	Baseline (Week 1 of BMN 190-201) to Week 289 / Last observation
Secondary	Total White Matter Volume	Percentage Change from Baseline to last observation: Total white matter volume	Baseline (Week 1 of BMN 190-201) to Week 289 / Last observation
Secondary	Whole Brain Apparent Diffusion Coefficient	Change from Baseline to last observation Whole brain apparent diffusion coefficient	Baseline (Week 1 of BMN 190-201) to Week 289 / Last observation