A Study of UX003 Recombinant Human Beta-Glucuronidase (rhGUS) Enzyme Replacement Therapy in Subjects With Mucopolysaccharidosis Type 7, Sly Syndrome (MPS 7)

NCT ID: NCT02432144

Last Updated: 2020-07-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-10
• Study Completion Date: 2019-01-14

Brief Summary

The primary objective of the study is to evaluate the long-term safety of UX003 in subjects with MPS 7.

Detailed Description

Participants with MPS 7 who were UX003 treatment-naïve or previously enrolled and treated in a prior clinical study of UX003 (e.g. UX003-CL301 [NCT02230566], investigator sponsored trials, expanded access/compassionate use) can enroll into this treatment and extension study provided all eligibility criteria is met for a given participant.

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

4 mg/kg UX003 every other week (QOW)

Group Type: EXPERIMENTAL

UX003

Intervention Type: DRUG

solution for intravenous (IV) infusion

Interventions

UX003

solution for intravenous (IV) infusion

Intervention Type: DRUG

Other Intervention Names

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

Eligibility Criteria

Inclusion Criteria

• Confirmed diagnosis of MPS 7 based on leukocyte or fibroblast glucuronidase enzyme assay or genetic testing.
• Willing and able to provide written, signed informed consent or, in the case of subjects under the age of 18 (or 16 years, depending on the region), provide written assent (if required) and written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures.
• Willing and able to comply with all study procedures.
• Sexually active subjects must be willing to use acceptable, highly-effective methods of contraception while participating in the study and for 30 days following the last dose.
• Females of childbearing potential must have a negative pregnancy test at Baseline and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have not experienced menarche, or have had tubal ligation at least one year prior to completion of the primary study, or have had total hysterectomy.
• For UX003 treatment-naïve subjects only, apparent clinical signs of lysosomal storage disease as judged by the Investigator, including at least one of the following: enlarged liver and spleen, joint limitations, airway obstruction or pulmonary problems, limitation of mobility while still ambulatory.
• For UX003 treatment-naïve subjects only, elevated urinary glycosaminoglycans (uGAG) excretion at a minimum of 2-fold over normal.
• For UX003 treatment-naïve subjects only, aged 5 years and older.

Exclusion Criteria

• If enrolled in a prior UX003 clinical study, the subject experienced safety-related event(s) in the prior UX003 clinical study that, in the opinion of the Investigator and sponsor, precludes resuming UX003 treatment.
• Undergone a successful bone marrow or stem cell transplant or has any degree of detectable chimaerism with donor cells.
• Presence or history of any hypersensitivity to rhGUS or its excipients that, in the judgment of the Investigator, places the subject at increased risk for adverse effects.
• Pregnant or breastfeeding at Baseline or planning to become pregnant (self or partner) at any time during the study.
• Other than the use of UX003, use of any investigational product (drug or device or combination) within 30 days prior to Baseline, or requirement for any investigational agent prior to completion of all scheduled study assessments.
• Presence of a condition of such severity and acuity that, in the opinion of the Investigator, warrants immediate surgical intervention or other treatment or may not allow safe study participation.
• Concurrent disease or condition, or laboratory abnormality 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 introduce additional safety concerns.

• Minimum 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 Pharmaceuticals, Inc.

Locations

Children's Hospital Oakland

Oakland, California, United States

Children's Hospital of Orange County

Orange, California, United States

University of Minnesota

Minneapolis, Minnesota, United States

Baylor College of Medicine

Houston, Texas, United States

Hospital Infantil Candido Fontoura Sao Paulo

São Paulo, , Brazil

Centenario Hospital Miguel Hidalgo, Pediatrics

Aguascalientes, , Mexico

Unidade de Doenças Metabólicas - Centro Hospitalar do Porto

Porto, , Portugal

Countries

United States; Brazil; Mexico; Portugal

References

Wang RY, da Silva Franco JF, Lopez-Valdez J, Martins E, Sutton VR, Whitley CB, Zhang L, Cimms T, Marsden D, Jurecka A, Harmatz P. The long-term safety and efficacy of vestronidase alfa, rhGUS enzyme replacement therapy, in subjects with mucopolysaccharidosis VII. Mol Genet Metab. 2020 Mar;129(3):219-227. doi: 10.1016/j.ymgme.2020.01.003. Epub 2020 Jan 11.

Reference Type: RESULT

PMID: 32063397 (View on PubMed)

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)

Tandon PK, Kakkis ED. The multi-domain responder index: a novel analysis tool to capture a broader assessment of clinical benefit in heterogeneous complex rare diseases. Orphanet J Rare Dis. 2021 Apr 19;16(1):183. doi: 10.1186/s13023-021-01805-5.

Reference Type: DERIVED

PMID: 33874971 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-001875-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

UX003-CL202

Identifier Type: -

Identifier Source: org_study_id