Back to resultsA Treatment Study of Mucopolysaccharidosis Type IIIB (MPS IIIB)
Primary Purpose
MPS III B, Mucopolysaccharidosis Type IIIB
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
AX 250
Sponsored by
About this trial
This is an interventional treatment trial for MPS III B focused on measuring Sanfilippo Syndrome Type B
Eligibility 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
Sites / Locations
- Children's Hospital Oakland
- Fundación Cardio Infantil - Instituto de Cardiología
- University Medical Center Hamburg Eppendorf, Department of Pediatrics
- Hospital Clinico Universitario de Santiago
- Mackay Memorial Hospital
- Gazi Üniversitesi Tıp Fakültesi
- Somers Clinical Research Facility, Great Ormond Street Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
AX 250
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Characterize maximum concentration (Cmax) of AX 250 in cerebrospinal fluid (CSF) and plasma as relevant through completion of Part 1 and 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
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
Evaluate GAG levels in cerebrospinal fluid (CSF)
Evaluate GAG levels in plasma
Evaluate GAG levels in urine
Evaluate the impact of AX 250 treatment on brain structure assessed by magnetic resonance imaging (MRI)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02754076
Brief Title
A Treatment Study of Mucopolysaccharidosis Type IIIB
Acronym
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)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
April 2016 (Actual)
Primary Completion Date
June 24, 2020 (Actual)
Study Completion Date
July 31, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Allievex Corporation
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
MPS III B, Mucopolysaccharidosis Type IIIB
Keywords
Sanfilippo Syndrome Type B
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AX 250
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
AX 250
Intervention Description
Chimeric fusion of recombinant human alpha-N-acetylglucosaminidase and truncated human insulin-like growth factor 2 (rhNAGLU-IGF2)
Primary Outcome Measure Information:
Title
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.
Description
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
Title
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 Measure Information:
Title
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.
Title
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.
Title
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
Title
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
Title
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
Title
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
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Allievex Medical Monitor
Organizational Affiliation
Allievex Corporation
Official's Role
Study Director
Facility Information:
Facility Name
Children's Hospital Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
Fundación Cardio Infantil - Instituto de Cardiología
City
Bogotá
Country
Colombia
Facility Name
University Medical Center Hamburg Eppendorf, Department of Pediatrics
City
Hamburg
Country
Germany
Facility Name
Hospital Clinico Universitario de Santiago
City
Santiago de Compostela
Country
Spain
Facility Name
Mackay Memorial Hospital
City
Taipei
ZIP/Postal Code
10449
Country
Taiwan
Facility Name
Gazi Üniversitesi Tıp Fakültesi
City
Ankara
Country
Turkey
Facility Name
Somers Clinical Research Facility, Great Ormond Street Hospital
City
London
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35709957
Citation
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.
Results Reference
derived
Learn more about this trial
A Treatment Study of Mucopolysaccharidosis Type IIIB
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