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

• ClinicalTrials.gov Identifier: NCT02485899
• Recruitment Status: Active, not recruiting
• First Posted: June 30, 2015
• Last Update Posted: October 2, 2019
• Sponsor: BioMarin Pharmaceutical
• Information provided by (Responsible Party): BioMarin Pharmaceutical

Study Description

Brief Summary:

The Phase 1/2 study (190-201) evaluated the efficacy and safety of doses up to 300 mg/every other week (qow) BMN 190 in 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 to receive continued BMN 190 treatment. The 190-202 study is an open label extension protocol to assess long-term safety and efficacy.

Condition or disease	Intervention/treatment	Phase
Jansky-Bielschowsky Disease; Batten Disease; Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2; CLN2 Disease; CLN2 Disorder	Biological: BMN 190; Device: Intraventricular Access Device	Phase 1; Phase 2

Detailed 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 restore TPP1 enzyme activity. BMN 190 is designed to reduce the progressive, pathologic accumulation of lysosomal storage material, and improve the symptoms of disease. The Phase 1/2 study (190-201) evaluated the efficacy and safety of doses up to 300 mg/every other week (qow) BMN 190 in 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 23 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Multinational, Extension Study to Evaluate the Long-Term Efficacy and Safety of BMN 190 in Patients With CLN2 Disease
• Actual Study Start Date: February 2015
• Estimated Primary Completion Date: July 2020
• Estimated Study Completion Date: January 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: BMN190 recombinant human tripeptidyl peptidase-1 (rhTPP1)	Biological: BMN 190; 300 mg ICV infusion administered every other week for up to 240 weeks; Other Names: recombinant human tripeptidyl peptidase-1 (rhTPP1); cerliponase alfa; Device: Intraventricular 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.

Outcome Measures

Primary Outcome Measures :

1. Long Term Safety as assessed by analysis of adverse events. [ Time Frame: up to 240 weeks ]
   Long term safety of BMN 190 administered to subjects with CLN2 disease via an implanted intracerebroventricular (ICV) reservoir and cannula as assessed by analysis of adverse events.
2. Motor and Language Changes [ Time Frame: up to 240 weeks ]
   Change in motor and language (ML) subscales of the CLN2 disease rating scale in patients with CLN2 following administration of 300 mg every other week of BMN 190.

Secondary Outcome Measures :

1. Quantitative Assessment of Magnetic Resonance Imaging [ Time Frame: up to 240 weeks ]
   Changes in quantitative assessment of MRI.
2. CLN2 Disease Scale Score [ Time Frame: up to 240 weeks ]
   Changes in the CLN2 disease scale total score
3. Quality of Life Changes [ Time Frame: up to 240 weeks ]
   Changes in the quality of life with long-term use of BMN 190

Eligibility Criteria

• Ages Eligible for Study: 3 Years to 16 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Ohio

Columbus, Ohio, United States

Germany

Hamburg, Germany

Italy

Rome, Italy

United Kingdom

London, United Kingdom

Sponsors and Collaborators

BioMarin Pharmaceutical

Investigators

• Study Director: Dave Jacoby, MD; BioMarin Pharmaceutical

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Schulz A, Ajayi T, Specchio N, de Los Reyes E, Gissen P, Ballon D, Dyke JP, Cahan H, Slasor P, Jacoby D, Kohlschütter A; CLN2 Study Group. Study of Intraventricular Cerliponase Alfa for CLN2 Disease. N Engl J Med. 2018 May 17;378(20):1898-1907. doi: 10.1056/NEJMoa1712649. Epub 2018 Apr 24.

• Responsible Party: BioMarin Pharmaceutical
• ClinicalTrials.gov Identifier: NCT02485899
• Other Study ID Numbers: 190-202
• First Posted: June 30, 2015
• Last Update Posted: October 2, 2019
• Last Verified: September 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes

Keywords provided by BioMarin Pharmaceutical:

Late infantile Neuronal Ceroid Lipofuscinosis Type 2; LINCL; NCL2; CLN2; Jansky-Bielschowsky disease

Additional relevant MeSH terms:

Neuronal Ceroid-Lipofuscinoses; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Lipidoses; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Metabolic Diseases