Study of UX003 Recombinant Human Beta-Glucuronidase (rhGUS) Enzyme Replacement Treatment in Mucopolysaccharidosis Type 7, Sly Syndrome (MPS 7) Patients Less Than 5 Years of Age

NCT02418455 | Completed Phase 2 Results

• 2 other identifiers: UX003-CL2032015-000104-26
• Study Type: interventional
• Target: 8
• Locations: 3 countries
• Sites: 5

Brief Summary

The primary objective was to evaluate the effect of UX003 treatment in pediatric MPS VII participants less than 5 years of age on safety, tolerability, and efficacy as determined by the reduction of urinary glycosaminoglycans (uGAG) excretion.

Conditions

Sly Syndrome; MPS VII; Mucopolysaccharidosis; Mucopolysaccharidosis VII

Keywords

MPS 7; Sly Syndrome; MPS VII; Enzyme Replacement Therapy; Rare Disease; Mucopolysaccharidosis type 7; Lysosomal Storage Disease; Metabolic Disorder

Outcome Measures

Primary Outcomes (2)

• Percent Change From Baseline in uGAG Excretion (LC-MS/MS-DS) at Week 48

  Liquid chromatography-mass spectrometry/mass spectrometry-dermatan sulfate (LS-MS/MS-DS) method. For the participant previously treated with UX003 under an eIND, percent change from initial baseline was used.

  Baseline (Week 0), Week 48

• Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs

  Adverse event (AE): any untoward medical occurrence in a participant, whether or not considered drug related. Serious AE (SAE): an AE or suspected adverse reaction that at any dose results in any of the following outcomes: death; a life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; a congenital anomaly/birth defect. Other important medical events may also, in the opinion of the Investigator, be considered SAEs. An AE was considered a TEAE if it occurred on or after the first dose, and was not present prior to the first dose, or it was present at the first dose but increased in severity during the study. Events recorded as either possibly, probably, or definitely related to treatment were categorized as related. AE severity was graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events, Version 4.03.

  From first dose of study drug until 30 days after the last dose of study drug. Mean (SD) treatment duration was 98.11 (29.02) weeks

Secondary Outcomes (9)

• Change From Baseline Over Time in Standing Height

  Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132

• Change From Baseline Over Time in Standing Height Z-Score

  Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132

• Change From Baseline Over Time in Head Circumference

  Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132

• Change From Baseline Over Time in Head Circumference Z-Score

  Baseline, Weeks 12, 24, 36, 48

• Change From Baseline Over Time in Weight

  Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132

Study Arms (1)

UX003

EXPERIMENTAL

UX003 4 mg/kg every other week (QOW). Initial treatment period 48 weeks. Continuation period up to 240 weeks.

Drug: UX003

Interventions

UX003 DRUG

solution for intravenous infusion

Also known as: recombinant human beta-glucuronidase, rhGUS, Mepsevii ™, vestronidase alfa-vjbk, vestronidase alfa

UX003

Eligibility Criteria

• Age: 1 Day - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Confirmed diagnosis of MPS 7 based on leukocyte or fibroblast glucuronidase enzyme assay, or genetic testing.
• Under 5 years of age at the time of informed consent.
• Written informed consent of Legally Authorized Representative after the nature of the study has been explained, and prior to any research-related procedures.

You may not qualify if:

• Undergone a successful bone marrow or stem cell transplant or has evidence of any degree of detectable chimaerism with donor cells.
• Any known hypersensitivity to rhGUS or its excipients that, in the judgment of the Investigator, places the subject at increased risk for adverse effects.
• Use of any investigational product (drug or device or combination) other than UX003 within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments at any time during the study.
• Has a condition of such severity and acuity, in the opinion of the Investigator, which may not allow safe study participation. For patients with hydrops fetalis, the ongoing interventions to manage fluid balance can be continued; if the addition of enzyme replacement therapy (ERT) is considered a fluid-overload risk, the individual should be excluded.
• Has a concurrent disease or condition that, in the view of the Investigator, places the subject at high risk of poor treatment compliance or of not completing the study, or would interfere with study participation or affect safety. Since hydropic patients have a high rate of mortality, the risk of death prior to 1 year of age should not be considered sufficient to exclude the patient from the study for compliance.

Sponsors & Collaborators

• Ultragenyx Pharmaceutical Inc: lead

Study Sites (5)

Children's National Health System

Washington D.C., District of Columbia, 20010, United States

Location

New York University Langone Medical Center

New York, New York, 10038, United States

Location

University of Utah Hospital

Salt Lake City, Utah, 84132, United States

Location

Centro Hospitalar do Porto

Porto, 4099-345, Portugal

Location

Hospital Universitario Virgen Del Rocio

Seville, 41013, Spain

Location

Related Publications (3)

• Montano AM, Rozdzynska-Swiatkowska A, Jurecka A, Ramirez AN, Zhang L, Marsden D, Wang RY, Harmatz P. Growth patterns in patients with mucopolysaccharidosis VII. Mol Genet Metab Rep. 2023 Jun 26;36:100987. doi: 10.1016/j.ymgmr.2023.100987. eCollection 2023 Sep.

  PMID: 37415957 DERIVED

• Lau HA, Viskochil D, Tanpaiboon P, Lopez AG, Martins E, Taylor J, Malkus B, Zhang L, Jurecka A, Marsden D. Long-term efficacy and safety of vestronidase alfa enzyme replacement therapy in pediatric subjects < 5 years with mucopolysaccharidosis VII. Mol Genet Metab. 2022 May;136(1):28-37. doi: 10.1016/j.ymgme.2022.03.002. Epub 2022 Mar 9.

  PMID: 35331634 DERIVED

• Qi Y, McKeever K, Taylor J, Haller C, Song W, Jones SA, Shi J. Pharmacokinetic and Pharmacodynamic Modeling to Optimize the Dose of Vestronidase Alfa, an Enzyme Replacement Therapy for Treatment of Patients with Mucopolysaccharidosis Type VII: Results from Three Trials. Clin Pharmacokinet. 2019 May;58(5):673-683. doi: 10.1007/s40262-018-0721-y.

  PMID: 30467742 DERIVED

MeSH Terms

Conditions

Mucopolysaccharidosis VII; Mucopolysaccharidoses; Rare Diseases; Lysosomal Storage Diseases; Metabolic Diseases

Interventions

vestronidase alfa

Condition Hierarchy (Ancestors)

Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Nutritional and Metabolic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Medical Information
• Organization: Ultragenyx Pharmaceutical Inc

medinfo@ultragenyx.com

1-888-756-8567

Study Officials

• Medical Director

  Ultragenyx Pharmaceutical Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: April 12, 2015
• First Posted: April 16, 2015
• Study Start: July 21, 2015
• Primary Completion: March 26, 2019
• Study Completion: March 26, 2019
• Last Updated: October 30, 2019
• Results First Posted: October 16, 2019

Record last verified: 2019-10

Locations

ES (1); US (3); PT (1)