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A Treatment Extension Study of Mucopolysaccharidosis Type IIIB

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ClinicalTrials.gov Identifier: NCT03784287
Recruitment Status : Enrolling by invitation
First Posted : December 21, 2018
Last Update Posted : December 21, 2018
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical

Brief Summary:
The primary objectives of this study are to evaluate the long-term safety and tolerability of BMN 250 administered to subjects with MPS IIIB by an implanted ICV reservoir and catheter and to evaluate the impact of long-term BMN 250 treatment on cognitive function in patients with MPS IIIB as assessed by developmental quotient (DQ).

Condition or disease Intervention/treatment Phase
Mucopolysaccharidosis Type IIIB MPS III B Drug: BMN 250 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 33 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 Safety and Efficacy of Intracerebroventricular BMN 250 in Patients With Mucopolysaccharidosis Type IIIB (MPS IIIB, Sanfilippo Syndrome Type B)
Actual Study Start Date : February 19, 2018
Estimated Primary Completion Date : October 2023
Estimated Study Completion Date : October 2024


Arm Intervention/treatment
Experimental: BMN 250
All subjects will receive BMN 250 at the MTTD established in 250-201, 300mg administered weekly by ICV infusion that will continue for up to 240 weeks.
Drug: BMN 250
Chimeric fusion of recombinant human alpha-N-acetylglucosaminidase and truncated human insulin-like growth factor 2 (rhNAGLU-IGF2)




Primary Outcome Measures :
  1. Evaluate the Long-term safety and tolerability of BMN 250 administered in up to 33 subjects with MPS IIIB by assessing the number of participants with abnormal clinical laboratory values and/or Adverse Events related to the treatment [ Time Frame: Entire study period, up to 240 weeks ]
  2. Evaluating the impact of long-term BMN 250 treatment on cognitive function in up to 33 patients with MPS IIIB as assessed by developmental quotient (DQ) [ Time Frame: Entire study period, up to 240 weeks ]

Secondary Outcome Measures :
  1. Evaluate the impact of long-term BMN 250 treatment on cognitive function in up to 33 patients with MPS IIIB as assessed by age equivalent score (AEq) [ Time Frame: Entire study period, up to 240 weeks ]
    Age equivalent score is derived from neurocognitive tests (Bayley Scales of Infant Development, 3rd edition OR Kaufman Assessment battery for Children, 2nd edition)

  2. Characterize immunogenicity as measured by IgE levels, formation of anti-BMN250, IGF1 and IGF2 antibodies in Cerebrospinal fluid (CSF) and serum. [ Time Frame: Entire study period, up to 240 weeks ]
  3. Evaluate the impact of long-term BMN 250 treatment on Heparan sulfate (HS) levels in cerebrospinal fluid (CSF), serum and urine. [ Time Frame: Entire study period, up to 240 weeks ]
  4. Evaluate the impact of long-term BMN 250 treatment on brain structure assessed by magnetic resonance imaging (MRI) [ Time Frame: Entire study period, up to 240 weeks ]
  5. Evaluate the impact of long-term BMN 250 treatment on adaptive function derived from the Vineland Adaptive Behavior Scales, 2nd edition (VABS-II) [ Time Frame: Entire study period, up to 240 weeks ]
    VABS-II is a measure of adaptive behavior and can be used to assess the level of subjects' functioning at various ages. Scale ranges from 0-4 (0 meaning never performs the behavior, and 4 meaning almost always performs the behavior independently)



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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have completed 48 weeks in Part 2 of Study 250-201 and enter 250-202 within 8 weeks of study completion
  • 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
  • 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 with childbearing potential, must have a negative pregnancy test at the Screening visit and be willing to have additional pregnancy tests during the study.

Exclusion Criteria:

  • Has both a DQ score < 20 and DQ score < 25% that of the 250-201 Baseline DQ score at the 250-201 Week 48 visit
  • Would not benefit from enrolling in the study in the opinion of the investigator
  • Has received stem cell, gene therapy or ERT (other than BMN 250) 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 other than BMN 250 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03784287


Locations
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United States, California
Children's Hospital and Research Center Oakland
Oakland, California, United States, 94609
Germany
University Medical Center Hamburg-Eppendorf
Hamburg, Germany
Spain
Complexo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario
Santiago de Compostela, Spain
Taiwan
MacKay Memorial Children's Hospital
Taipei, Taiwan
Turkey
Gazi University Faculty of Medicine
Ankara, Turkey
United Kingdom
Great Ormond Street Hospital For Children, NHS Foundation Trust
London, United Kingdom, WC1N 3JH
Sponsors and Collaborators
BioMarin Pharmaceutical
Investigators
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Study Director: Medical Monitor, MD BioMarin Pharmaceutical

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Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT03784287     History of Changes
Other Study ID Numbers: BMN 250-202
First Posted: December 21, 2018    Key Record Dates
Last Update Posted: December 21, 2018
Last Verified: December 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by BioMarin Pharmaceutical:
Sanfilippo Syndrome Type B

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