A Treatment Study of Mucopolysaccharidosis Type IIIB

Mucopolysaccharidosis Type IIIB Clinical Trial

— MPS IIIB  

Official 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02754076
• Other study ID #: 250-201
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 2016
• Est. completion date: July 31, 2020

Study information

• Verified date: August 2020
• Source: Allievex Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: July 31, 2020
• Est. primary completion date: June 24, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 10 Years

Eligibility

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

Related Conditions & MeSH terms

• MPS III B
• Mucopolysaccharidoses
• Mucopolysaccharidosis III
• Mucopolysaccharidosis Type IIIB

Intervention

Drug:
• AX 250
Chimeric fusion of recombinant human alpha-N-acetylglucosaminidase and truncated human insulin-like growth factor 2 (rhNAGLU-IGF2)

Locations

Country	Name	City	State
Colombia	Fundación Cardio Infantil - Instituto de Cardiología	Bogotá
Germany	University Medical Center Hamburg Eppendorf, Department of Pediatrics	Hamburg
Spain	Hospital Clinico Universitario de Santiago	Santiago de Compostela
Taiwan	Mackay Memorial Hospital	Taipei
Turkey	Gazi Üniversitesi Tip Fakültesi	Ankara
United Kingdom	Somers Clinical Research Facility, Great Ormond Street Hospital	London
United States	Children's Hospital Oakland	Oakland	California

Sponsors (1)

Lead Sponsor	Collaborator
Allievex Corporation

Countries where clinical trial is conducted

United States,  Colombia,  Germany,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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.
Secondary	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.
Secondary	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
Secondary	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
Secondary	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
Secondary	Evaluate GAG levels in urine		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
Secondary	Evaluate the impact of AX 250 treatment on brain structure assessed by magnetic resonance imaging (MRI)		Assessed at study end, up to 124 weeks. Part 1 - Screening and Baseline; Part 2 - Screening, Baseline, Week 24, and Week 48