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

NCT ID: NCT02418455

Last Updated: 2019-10-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-21
• Study Completion Date: 2019-03-26

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

UX003

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

Group Type: EXPERIMENTAL

UX003

Intervention Type: DRUG

solution for intravenous infusion

Interventions

UX003

solution for intravenous infusion

Intervention Type: DRUG

Other Intervention Names

recombinant human beta-glucuronidase; rhGUS; Mepsevii ™; vestronidase alfa-vjbk; vestronidase alfa

Eligibility Criteria

Inclusion Criteria

1. Confirmed diagnosis of MPS 7 based on leukocyte or fibroblast glucuronidase enzyme assay, or genetic testing.

2. Under 5 years of age at the time of informed consent.

3. Written informed consent of Legally Authorized Representative after the nature of the study has been explained, and prior to any research-related procedures.

Exclusion Criteria

1. Undergone a successful bone marrow or stem cell transplant or has evidence of any degree of detectable chimaerism with donor cells.

2. Any known hypersensitivity to rhGUS or its excipients that, in the judgment of the Investigator, places the subject at increased risk for adverse effects.

3. 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.

4. 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.

5. 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.

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ultragenyx Pharmaceutical Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Ultragenyx Pharmaceutical Inc

Locations

Children's National Health System

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

New York University Langone Medical Center

New York, New York, United States

University of Utah Hospital

Salt Lake City, Utah, United States

Centro Hospitalar do Porto

Porto, , Portugal

Hospital Universitario Virgen Del Rocio

Seville, , Spain

Countries

United States; Portugal; Spain

References

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.

Reference Type: DERIVED

PMID: 37415957 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35331634 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30467742 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-000104-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

UX003-CL203

Identifier Type: -

Identifier Source: org_study_id