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A Treatment Study of Mucopolysaccharidosis Type IIIB (MPS IIIB)

This study is currently recruiting participants.
See Contacts and Locations
Verified August 2017 by BioMarin Pharmaceutical
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT02754076
First received: February 27, 2016
Last updated: August 30, 2017
Last verified: August 2017
  Purpose
The study's primary objectives are to evaluate the safety and tolerability of BMN 250 administered to subjects with MPS IIIB via an ICV reservoir and catheter and to evaluate the impact of BMN 250 on cognitive function in patients with MPS IIIB as assessed by the Development Quotient.

Condition Intervention Phase
MPS III B Mucopolysaccharidosis Type IIIB Drug: BMN 250 Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Open-Label Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Intracerebroventricular BMN 250 in Patients With Mucopolysaccharidosis Type IIIB (MPS IIIB, Sanfilippo Syndrome Type B)

Resource links provided by NLM:


Further study details as provided by BioMarin Pharmaceutical:

Primary Outcome Measures:
  • Safety Evaluation of weekly infusions of BMN 250 (Part 1 & Part 2) - Number of participants with abnormal clinical laboratory values and/or Adverse Events that are related to treatment. [ Time Frame: Entire study period, up to 124 weeks ]
    Number of participants with abnormal clinical laboratory values and/or Adverse Events that are related to treatment.

  • Development Quotient (DQ) as efficacy variable with analysis of rate of change of DQ score on treatment vs. rate of change of DQ score prior to treatment. [ Time Frame: Assessed at study end, up to 124 weeks. Collected at: Part 1 - Baseline; Part 2 - Weeks 12, 24, 36, & 48 ]

Secondary Outcome Measures:
  • Characterize maximum concentration (Cmax) of BMN 250 in cerebrospinal fluid (CSF) and plasma as relevant through completion of Part 1 and Part 2 [ Time Frame: Study end, up to 124 weeks. Collected at: Pre-dose, 0, 4, 10, 24, 48, 72, 96, 168 hours post-dose for the first dose during each dose escalation in Part 1. Pre-dose, 0, 4, 10, 24, 48, 72, 96, 168 hours post-dose for Baseline, Weeks 5, 12, 36 in Part 2. ]
  • Characterize area under concentration curve (AUC) of BMN 250 in cerebrospinal fluid (CSF) and plasma as relevant through completion of Part 1 and Part 2 [ Time Frame: Study end, up to 124 weeks. Collected at: Pre-dose, 0, 4, 10, 24, 48, 72, 96, 168 hours post-dose for the first dose during each dose escalation in Part 1. Pre-dose, 0, 4, 10, 24, 48, 72, 96, 168 hours post-dose for Baseline, Weeks 5, 12, 36 in Part 2. ]
  • Characterize immunogenicity of BMN 250 total anti-drug anti-body (TAb) in cerebrospinal fluid (CSF) and serum as relevant through completion of Part 1 and Part 2 [ Time Frame: Assessed at study end, up to 124 weeks. Collected at: First dose during each dose escalation in Part 1, and Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 in Part 2 ]
  • Evaluate GAG levels in cerebrospinal fluid (CSF) [ Time Frame: Assessed at study end, up to 124 weeks. Collected at: Each weekly visit as relevant through completion of Part 1 and Part 2 ]
  • Evaluate GAG levels in plasma [ Time Frame: Assessed at study end, up to 124 weeks. Collected at: Each weekly visit as relevant through completion of Part 1 and Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, as relevant in Part 2 ]
  • Evaluate GAG levels in urine [ Time Frame: Assessed at study end, up to 124 weeks. Collected at: Each weekly visit as relevant through completion of Part 1 and Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, as relevant in Part 2 ]
  • Evaluate the impact of BMN 250 treatment on brain structure assessed by magnetic resonance imaging (MRI) [ Time Frame: Assessed at study end, up to 124 weeks. Part 1 - Screening and Baseline; Part 2 - Screening, Baseline, Week 24, and Week 48 ]

Estimated Enrollment: 33
Study Start Date: April 2016
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BMN 250
In Part 1, patients will receive up to 3 escalating doses of BMN 250 (30, 100 and 300 mg) via ICV infusion every week until the maximum tolerated tested dose (MTTD) is established. In Part 2, patients will receive weekly doses of BMN250 via ICV infusion that will continue for 48 weeks at the MTTD established in Part 1.
Drug: BMN 250
Chimeric fusion of recombinant human alpha-N-acetylglucosaminidase and truncated human insulin-like growth factor 2 (rhNAGLU-IGF2)

  Eligibility

Ages Eligible for Study:   1 Year to 10 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Individuals eligible to participate in Part 1 of this study must meet all of the following criteria:

  • Has deficient NAGLU enzyme activity at Screening. Blood for NAGLU enzyme activity will be collected and analyzed centrally.
  • Is ≥ 1 and < 11 years of age (at least 1 of the 3 subjects in Part 1 must be ≥ 1 and < 6 years of age)
  • Has presented with signs/symptoms consistent with MPS IIIB; for individuals who have not presented with signs/symptoms of disease (eg, siblings of known patients), the determination of eligibility will be at the discretion of the BioMarin medical monitor in conjunction with the site investigator.
  • Written informed consent from parent or legal guardian and assent from subject, if required
  • Has the ability to comply with protocol requirements, in the opinion of the investigator

Individuals eligible to participate in Part 2 of this study must meet all of the following criteria:

  • Participated in and met protocol requirements for transitioning from Study 250-901 or participated in Part 1 of Study 250-201
  • Written informed consent from parent or legal guardian and assent from subject, if required

Exclusion Criteria:

Individuals who meet any of the following exclusion criteria are ineligible to participate in Part 1 of the study:

  • Has received stem cell, gene therapy or ERT for MPS IIIB
  • Has contraindications for neurosurgery (eg, congenital heart disease, severe respiratory impairment, or clotting abnormalities)
  • Has contraindications for MRI scans (eg, cardiac pacemaker, metal fragment or chip in the eye, or aneurysm clip in the brain)
  • Has a history of poorly controlled seizure disorder
  • Is prone to complications from intraventricular drug administration, including patients with hydrocephalus or ventricular shunts
  • Has received any investigational medication within 30 days prior to the Baseline visit or is scheduled to receive any investigational drug 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 protocol requirements, the subject's well-being or safety, or the interpretability of the subject's clinical data.
  • Is pregnant at any time during the study

Individuals who meet any of the following exclusion criteria are ineligible to participate in Part 2 of this study:

  • Has received stem cell, gene therapy or ERT for MPS IIIB
  • Has contraindications for neurosurgery (eg, congenital heart disease, severe respiratory impairment, or clotting abnormalities)
  • Has contraindications for MRI scans (eg, cardiac pacemaker, metal fragment or chip in the eye, or aneurysm clip in the brain)
  • Is prone to complications from intraventricular drug administration, including patients with hydrocephalus or ventricular shunts
  • Has received any investigational medication within 30 days prior to the Baseline visit or is scheduled to receive any investigational drug 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 protocol requirements, the subject's well-being or safety, or the interpretability of the subject's clinical data.
  • Is pregnant at any time during the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02754076

Contacts
Contact: BioMarin Trial Inquiries medinfo@bmrn.com

Locations
Germany
University Medical Center Hamburg Eppendorf, Department of Pediatrics Recruiting
Hamburg, Germany
Spain
Hospital Clinico Universitario de Santiago Recruiting
Santiago de Compostela, Spain
Taiwan
Mackay Memorial Hospital Recruiting
Taipei, Taiwan, 10449
United Kingdom
Somers Clinical Research Facility, Great Ormond Street Hospital Recruiting
London, United Kingdom
Sponsors and Collaborators
BioMarin Pharmaceutical
Investigators
Study Director: BioMarin Medical Monitor BioMarin Pharmaceutical
  More Information

Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT02754076     History of Changes
Other Study ID Numbers: 250-201
Study First Received: February 27, 2016
Last Updated: August 30, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by BioMarin Pharmaceutical:
Sanfilippo Syndrome Type B

Additional relevant MeSH terms:
Mucopolysaccharidoses
Mucopolysaccharidosis III
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases

ClinicalTrials.gov processed this record on September 21, 2017