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Completed

NCT Number: NCT02754076

A Treatment Study of Mucopolysaccharidosis Type IIIB

The study's primary objectives are to evaluate the safety and tolerability of AX 250 administered to subjects with MPS IIIB via an ICV reservoir and catheter and to evaluate the impact of AX 250 on cognitive function in patients with MPS IIIB as assessed by the Development Quotient.

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Key information

Conditions

MPS III B Carbohydrate Metabolism, Inborn Errors Congenital, Hereditary, and Neonatal Diseases and Abnormalities Connective Tissue Diseases Genetic Diseases, Inborn Lysosomal Storage Diseases Metabolic Diseases Metabolism, Inborn Errors Mucinoses Mucopolysaccharidoses Mucopolysaccharidosis III Mucopolysaccharidosis Type IIIB Nutritional and Metabolic Diseases Skin and Connective Tissue Diseases

Age range

1 year–10 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Fundación Cardio Infantil - Instituto de Cardiología, Bogotá, Colombia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

AX 250

Drug

Chimeric fusion of recombinant human alpha-N-acetylglucosaminidase and truncated human insulin-like growth factor 2 (rhNAGLU-IGF2)

Primary outcomes

  1. Safety Evaluation of weekly infusions of AX 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.

  2. 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 outcomes

  1. Characterize maximum concentration (Cmax) of AX 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.

  2. Characterize area under concentration curve (AUC) of AX 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.

  3. Characterize immunogenicity of AX 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

  4. 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

  5. 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

  6. 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

  7. Evaluate the impact of AX 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

Sponsors and collaborators

Lead sponsor

Allievex Corporation

Industry

Registry information

Official study title

A Phase 1/2 Open-Label Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Intracerebroventricular AX 250 in Patients With Mucopolysaccharidosis Type IIIB (MPS IIIB, Sanfilippo Syndrome Type B)

Acronym: MPS IIIB

Important dates

Study start
2016
Primary completion
2020
Study completion
2020
First posted
Apr 28, 2016
Registry last updated
Aug 6, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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