A Treatment Study of Mucopolysaccharidosis Type IIIB

NCT02754076 | Completed Phase 1

• 1 other identifier: 250-201
• Study Type: interventional
• Target: 23
• Locations: 7 countries
• Sites: 7

Brief Summary

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.

Conditions

MPS III B; Mucopolysaccharidosis Type IIIB

Keywords

Sanfilippo Syndrome Type B

Outcome Measures

Primary Outcomes (2)

• 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.

  Number of participants with abnormal clinical laboratory values and/or Adverse Events that are related to treatment.

  Entire study period, up to 124 weeks

• 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.

  Assessed at study end, up to 124 weeks. Collected at: Part 1 - Baseline; Part 2 - Weeks 12, 24, 36, & 48

Secondary Outcomes (7)

• Characterize maximum concentration (Cmax) of AX 250 in cerebrospinal fluid (CSF) and plasma as relevant through completion of Part 1 and Part 2

  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 AX 250 in cerebrospinal fluid (CSF) and plasma as relevant through completion of Part 1 and Part 2

  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 AX 250 total anti-drug anti-body (TAb) in cerebrospinal fluid (CSF) and serum as relevant through completion of Part 1 and Part 2

  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)

  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

  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

Study Arms (1)

AX 250

EXPERIMENTAL

In Part 1, patients will receive up to 3 escalating doses of AX 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 AX 250 via ICV infusion that will continue for 48 weeks at the MTTD established in Part 1.

Drug: AX 250

Interventions

AX 250 DRUG

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

AX 250

Eligibility Criteria

• Age: 1 Year - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Allievex Corporation: lead

Study Sites (7)

Children's Hospital Oakland

Oakland, California, 94609, United States

Location

Fundación Cardio Infantil - Instituto de Cardiología

Bogotá, Colombia

Location

University Medical Center Hamburg Eppendorf, Department of Pediatrics

Hamburg, Germany

Location

Hospital Clinico Universitario de Santiago

Santiago de Compostela, Spain

Location

Mackay Memorial Hospital

Taipei, 10449, Taiwan

Location

Gazi Üniversitesi Tıp Fakültesi

Ankara, Turkey (Türkiye)

Location

Somers Clinical Research Facility, Great Ormond Street Hospital

London, United Kingdom

Location

Related Publications (2)

• Muschol N, Koehn A, von Cossel K, Okur I, Ezgu F, Harmatz P, de Castro Lopez MJ, Couce ML, Lin SP, Batzios S, Cleary M, Solano M, Nestrasil I, Kaufman B, Shaywitz AJ, Maricich SM, Kuca B, Kovalchin J, Zanelli E. A phase I/II study on intracerebroventricular tralesinidase alfa in patients with Sanfilippo syndrome type B. J Clin Invest. 2023 Jan 17;133(2):e165076. doi: 10.1172/JCI165076.

  PMID: 36413418 DERIVED

• Okur I, Ezgu F, Giugliani R, Muschol N, Koehn A, Amartino H, Harmatz P, de Castro Lopez MJ, Couce ML, Lin SP, Batzios S, Cleary M, Solano M, Peters H, Lee J, Nestrasil I, Shaywitz AJ, Maricich SM, Kuca B, Kovalchin J, Zanelli E. Longitudinal Natural History of Pediatric Subjects Affected with Mucopolysaccharidosis IIIB. J Pediatr. 2022 Oct;249:50-58.e2. doi: 10.1016/j.jpeds.2022.06.005. Epub 2022 Jun 13.

  PMID: 35709957 DERIVED

MeSH Terms

Conditions

Mucopolysaccharidosis III

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Allievex Medical Monitor

  Allievex Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2016
• First Posted: April 28, 2016
• Study Start: April 1, 2016
• Primary Completion: June 24, 2020
• Study Completion: July 31, 2020
• Last Updated: August 6, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); DE (1); US (1); ES (1); CO (1); TW (1); TU (1)