MPS III BPhase 1/2MPS IIIBNCT02754076
A Treatment Study of Mucopolysaccharidosis Type IIIB
A Phase 1/2 study testing AX 250 in people with MPS III B and Mucopolysaccharidosis Type IIIB, run by Allievex Corporation at 7 sites in 7 countries.
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. Read more about this study
- Who is it for?
- Ages 1 year to 10 years
- Conditions the study is for
- MPS III B, Mucopolysaccharidosis Type IIIB
- What is being tested?
- AX 250
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 7 sitesin 7 countries
- Study dates
- Apr 2016to 31 Jul 2020
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 10 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
7 sites in 7 countries.
7 sites in 7 countries
United States1 site
Children's Hospital Oakland
Oakland, California, 94609
Germany1 site
University Medical Center Hamburg Eppendorf, Department of Pediatrics
Hamburg
United Kingdom1 site
Somers Clinical Research Facility, Great Ormond Street Hospital
London
About this study
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)
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
- Being tested
- AX 250
- Keywords
- Sanfilippo Syndrome Type B
- Medical subject headings
- Mucopolysaccharidosis III
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AX 250Drug
Chimeric fusion of recombinant human alpha-N-acetylglucosaminidase and truncated human insulin-like growth factor 2 (rhNAGLU-IGF2)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: AX 250 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: 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
Measured: 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 GAG levels in urine
Measured: 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)
Measured: Assessed at study end, up to 124 weeks. Part 1 - Screening and Baseline; Part 2 - Screening, Baseline, Week 24, and Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2016 (estimated)
- Study startApr 2016
- Primary completion24 Jun 2020
- Study completion31 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for MPS III BStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Allievex Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Allievex Medical Monitor, Study director, Allievex Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02754076
- Sponsor's protocol ID
- 250-201
- Acronym
- MPS IIIB
- Status last verified
- Aug 2020
- First submitted
- 27 Feb 2016
- Last updated
- 6 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 36413418Okur 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.
PubMed 35709957
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02754076
- Acronym / sponsor ID
- MPS IIIB / 250-201
- Conditions
- MPS III B, Mucopolysaccharidosis Type IIIB
- Keywords
- Sanfilippo Syndrome Type B
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Allievex CorporationIndustry (pharma, biotech, devices)
- Study start
- Apr 2016 (actual)
- Primary completion
- 24 Jun 2020 (actual)
- Study completion
- 31 Jul 2020 (actual)
- First posted
- 28 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AX 250 | Experimental | Drug: AX 250In 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. |
Who may qualify
- Ages
- 1 year to 10 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AX 250Chimeric fusion of recombinant human alpha-N-acetylglucosaminidase and truncated human insulin-like growth factor 2 (rhNAGLU-IGF2) | Drug | AX 250 |
Primary outcome
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.
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
7 secondary outcomes
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.
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.
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
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
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2020.
- Derived from this study: PubMed 36413418Muschol 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.
- Derived from this study: PubMed 35709957Okur 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Allievex Medical Monitor study director
Allievex Corporation
7 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AX 250 in people with MPS III B and Mucopolysaccharidosis Type IIIB, run by Allievex Corporation at 7 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Colombia, Germany, Spain, Taiwan and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02754076, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2020; AzTrials last refreshed its copy on 7 Nov 2026.