Back to results

A Treatment Extension Study of Mucopolysaccharidosis Type IIIB

Primary Purpose

Mucopolysaccharidosis Type IIIB, MPS III B

Status

Active

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

AX 250

About this trial

This is an interventional treatment trial for Mucopolysaccharidosis Type IIIB focused on measuring Sanfilippo Syndrome Type B

Eligibility Criteria

0 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Must have completed 48 weeks in Part 2 of Study 250-201 and enter 250-202 within 8 weeks of study completion
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
Males and females who are of reproductive age should practice true abstinence, defined as no sexual activity, during the study and for 6 months after the study has been completed (or withdrawal from the study). If sexually active and not practicing true abstinence, males and females of reproductive age must use a highly effective method of contraception while participating in the study.
If female with childbearing potential, must have a negative pregnancy test at the Screening visit and be willing to have additional pregnancy tests during the study.

Exclusion Criteria:

Has both (1) a cognitive AEq score ≤ 18 months, and (2) a DQ score ≤ 20
Would not benefit from enrolling in the study in the opinion of the investigator
Has received stem cell, gene therapy or ERT (other than AX 250) 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 other than AX 250 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 and Research Center Oakland
UPMC Children's Hospital Pittburgh
Fundación Cardio Infantil - Instituto de Cardiología
University Medical Center Hamburg-Eppendorf
Complexo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario
MacKay Memorial Children's Hospital
Gazi University Faculty of Medicine
Great Ormond Street Hospital For Children, NHS Foundation Trust

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AX 250

Arm Description

All subjects will receive AX 250 at the MTTD established in 250-201, 300mg administered weekly by ICV infusion that will continue for up to 240 weeks.

Outcomes

Primary Outcome Measures

Evaluate the Long-term safety and tolerability of AX 250 administered in up to 33 subjects with MPS IIIB by assessing the number of participants with abnormal clinical laboratory values and/or Adverse Events related to the treatment

Evaluating the impact of long-term AX 250 treatment on cognitive function in up to 33 patients with MPS IIIB as assessed by developmental quotient (DQ)

Secondary Outcome Measures

Evaluate the impact of long-term AX 250 treatment on cognitive function in up to 33 patients with MPS IIIB as assessed by age equivalent score (AEq)

Age equivalent score is derived from neurocognitive tests (Bayley Scales of Infant Development, 3rd edition OR Kaufman Assessment battery for Children, 2nd edition)

Characterize immunogenicity as measured by IgE levels, formation of anti-AX 250, IGF1 and IGF2 antibodies in Cerebrospinal fluid (CSF) and serum.

Evaluate the impact of long-term AX 250 treatment on Heparan sulfate (HS) levels in cerebrospinal fluid (CSF), serum and urine.

Evaluate the impact of long-term AX 250 treatment on brain structure assessed by magnetic resonance imaging (MRI)

Evaluate the impact of long-term AX 250 treatment on adaptive function derived from the Vineland Adaptive Behavior Scales, 2nd edition (VABS-II)

VABS-II is a measure of adaptive behavior and can be used to assess the level of subjects' functioning at various ages. Scale ranges from 0-4 (0 meaning never performs the behavior, and 4 meaning almost always performs the behavior independently)

Full Information

NCT ID

NCT03784287

First Posted

March 30, 2018

Last Updated

January 16, 2023

Sponsor

Allievex Corporation

1. Study Identification

Unique Protocol Identification Number

NCT03784287

Brief Title

A Treatment Extension Study of Mucopolysaccharidosis Type IIIB

Official Title

A Multicenter, Multinational, Extension Study to Evaluate the Long Term Safety 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

October 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

February 19, 2018 (Actual)

Primary Completion Date

January 2025 (Anticipated)

Study Completion Date

February 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Allievex Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

Brief Summary

The primary objectives of this study are to evaluate the long-term safety and tolerability of AX 250 administered to subjects with MPS IIIB by an implanted ICV reservoir and catheter and to evaluate the impact of long-term AX 250 treatment on cognitive function in patients with MPS IIIB as assessed by developmental quotient (DQ).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Mucopolysaccharidosis Type IIIB, MPS III B

Keywords

Sanfilippo Syndrome Type B

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

AX 250

Arm Type

Experimental

Arm Description

All subjects will receive AX 250 at the MTTD established in 250-201, 300mg administered weekly by ICV infusion that will continue for up to 240 weeks.

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

Time Frame

Entire study period, up to 240 weeks

Title

Evaluating the impact of long-term AX 250 treatment on cognitive function in up to 33 patients with MPS IIIB as assessed by developmental quotient (DQ)

Time Frame

Entire study period, up to 240 weeks

Secondary Outcome Measure Information:

Title

Evaluate the impact of long-term AX 250 treatment on cognitive function in up to 33 patients with MPS IIIB as assessed by age equivalent score (AEq)

Description

Age equivalent score is derived from neurocognitive tests (Bayley Scales of Infant Development, 3rd edition OR Kaufman Assessment battery for Children, 2nd edition)

Time Frame

Entire study period, up to 240 weeks

Title

Characterize immunogenicity as measured by IgE levels, formation of anti-AX 250, IGF1 and IGF2 antibodies in Cerebrospinal fluid (CSF) and serum.

Time Frame

Entire study period, up to 240 weeks

Title

Evaluate the impact of long-term AX 250 treatment on Heparan sulfate (HS) levels in cerebrospinal fluid (CSF), serum and urine.

Time Frame

Entire study period, up to 240 weeks

Title

Evaluate the impact of long-term AX 250 treatment on brain structure assessed by magnetic resonance imaging (MRI)

Time Frame

Entire study period, up to 240 weeks

Title

Evaluate the impact of long-term AX 250 treatment on adaptive function derived from the Vineland Adaptive Behavior Scales, 2nd edition (VABS-II)

Description

Time Frame

Entire study period, up to 240 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

0 Years

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Must have completed 48 weeks in Part 2 of Study 250-201 and enter 250-202 within 8 weeks of study completion 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 Males and females who are of reproductive age should practice true abstinence, defined as no sexual activity, during the study and for 6 months after the study has been completed (or withdrawal from the study). If sexually active and not practicing true abstinence, males and females of reproductive age must use a highly effective method of contraception while participating in the study. If female with childbearing potential, must have a negative pregnancy test at the Screening visit and be willing to have additional pregnancy tests during the study. Exclusion Criteria: Has both (1) a cognitive AEq score ≤ 18 months, and (2) a DQ score ≤ 20 Would not benefit from enrolling in the study in the opinion of the investigator Has received stem cell, gene therapy or ERT (other than AX 250) 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 other than AX 250 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

Medical Monitor, MD

Organizational Affiliation

Allievex Corporation

Official's Role

Study Director

Facility Information:

Facility Name

Children's Hospital and Research Center Oakland

City

Oakland

State/Province

California

ZIP/Postal Code

94609

Country

United States

Facility Name

UPMC Children's Hospital Pittburgh

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15224

Country

United States

Facility Name

Fundación Cardio Infantil - Instituto de Cardiología

City

Bogotá,

Country

Colombia

Facility Name

University Medical Center Hamburg-Eppendorf

City

Hamburg

Country

Germany

Facility Name

Complexo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario

City

Santiago de Compostela

Country

Spain

Facility Name

MacKay Memorial Children's Hospital

City

Taipei

Country

Taiwan

Facility Name

Gazi University Faculty of Medicine

City

Ankara

Country

Turkey

Facility Name

Great Ormond Street Hospital For Children, NHS Foundation Trust

City

London

ZIP/Postal Code

WC1N 3JH

Country

United Kingdom

12. IPD Sharing Statement

Learn more about this trial

A Treatment Extension Study of Mucopolysaccharidosis Type IIIB

We'll reach out to this number within 24 hrs