A Treatment Extension Study of Mucopolysaccharidosis Type IIIB

NCT03784287 | Unknown Phase 2 FDA Drug

• 1 other identifier: AX 250-202
• Study Type: interventional
• Target: 20
• Locations: 7 countries
• Sites: 8

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).

Conditions

Mucopolysaccharidosis Type IIIB; MPS III B

Keywords

Sanfilippo Syndrome Type B

Outcome Measures

Primary Outcomes (2)

• 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

  Entire study period, up to 240 weeks

• 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)

  Entire study period, up to 240 weeks

Secondary Outcomes (5)

• 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)

  Entire study period, up to 240 weeks

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

  Entire study period, up to 240 weeks

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

  Entire study period, up to 240 weeks

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

  Entire study period, up to 240 weeks

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

  Entire study period, up to 240 weeks

Study Arms (1)

AX 250

EXPERIMENTAL

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.

Drug: AX 250

Interventions

AX 250 DRUG

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

AX 250

Eligibility Criteria

• Age: 0 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Allievex Corporation: lead

Study Sites (8)

Children's Hospital and Research Center Oakland

Oakland, California, 94609, United States

Location

UPMC Children's Hospital Pittburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Fundación Cardio Infantil - Instituto de Cardiología

Bogotá, Colombia

Location

University Medical Center Hamburg-Eppendorf

Hamburg, Germany

Location

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

Santiago de Compostela, Spain

Location

MacKay Memorial Children's Hospital

Taipei, Taiwan

Location

Gazi University Faculty of Medicine

Ankara, Turkey (Türkiye)

Location

Great Ormond Street Hospital For Children, NHS Foundation Trust

London, WC1N 3JH, United Kingdom

Location

MeSH Terms

Conditions

Mucopolysaccharidosis III

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Medical Monitor, MD

  Allievex Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2018
• First Posted: December 21, 2018
• Study Start: February 19, 2018
• Primary Completion: January 1, 2025
• Study Completion: February 1, 2025
• Last Updated: January 18, 2023

Record last verified: 2022-10

Locations

TW (1); TU (1); GB (1); CO (1); DE (1); US (2); ES (1)