MPS III B, Mucopolysaccharidosis Type IIIB
Conditions
Keywords
Sanfilippo Syndrome Type B
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.
Interventions
DRUGAX 250
Chimeric fusion of recombinant human alpha-N-acetylglucosaminidase and truncated human insulin-like growth factor 2 (rhNAGLU-IGF2)
Sponsors
Allievex Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 10 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Entire study period, up to 124 weeks | 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. | Assessed at study end, up to 124 weeks. Collected at: Part 1 - Baseline; Part 2 - Weeks 12, 24, 36, & 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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. |
| 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 |
| 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 |
| 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 |
| 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. |
Countries
Colombia, Germany, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Outcome results
None listed