A Phase 3 Study of UX003 Recombinant Human Betaglucuronidase (rhGUS) Enzyme Replacement Therapy in Patients With Mucopolysaccharidosis Type 7 (MPS 7)

NCT ID: NCT02230566

Last Updated: 2020-07-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-31
• Study Completion Date: 2016-05-31

Brief Summary

The Phase 3 study will use a novel randomized, intra-subject placebo-controlled, single crossover design, referred to as Blind Start, to evaluate the safety and efficacy of UX003. The Blind Start is a novel design whereby participants will be randomized to 1 of 4 groups, each representing a different treatment sequence, and will cross over to UX003 at different pre-defined time points in a blinded manner. All groups will receive a minimum of 24 weeks treatment with 4 mg/kg UX003 every other week (QOW).

Conditions

MPS 7; Sly Syndrome; Mucopolysaccharidosis; MPS VII

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Group A: 4 mg/kg UX003

4 mg/kg UX003 QOW through Week 46

Group Type: EXPERIMENTAL

UX003

Intervention Type: DRUG

UX003 is a sterile concentrate formulation of rhGUS for intravenous infusion

Group B: 8 Weeks Placebo then 4 mg/kg UX003

Placebo QOW for the first 8 weeks followed by 4 mg/kg UX003 QOW through Week 46

Group Type: EXPERIMENTAL

UX003

Intervention Type: DRUG

UX003 is a sterile concentrate formulation of rhGUS for intravenous infusion

Placebo

Intervention Type: OTHER

Placebo consisting of the UX003 formulation buffer (without rhGUS)

Group C: 16 Weeks Placebo then 4 mg/kg UX003

Placebo QOW for the first 16 weeks followed by 4 mg/kg UX003 QOW through Week 46

Group Type: EXPERIMENTAL

UX003

Intervention Type: DRUG

UX003 is a sterile concentrate formulation of rhGUS for intravenous infusion

Placebo

Intervention Type: OTHER

Placebo consisting of the UX003 formulation buffer (without rhGUS)

Group D: 24 Weeks Placebo then 4 mg/kg UX003

Placebo QOW for the first 24 weeks followed by 4 mg/kg UX003 QOW through Week 46

Group Type: EXPERIMENTAL

UX003

Intervention Type: DRUG

UX003 is a sterile concentrate formulation of rhGUS for intravenous infusion

Placebo

Intervention Type: OTHER

Placebo consisting of the UX003 formulation buffer (without rhGUS)

Interventions

UX003

UX003 is a sterile concentrate formulation of rhGUS for intravenous infusion

Intervention Type: DRUG

Placebo

Placebo consisting of the UX003 formulation buffer (without rhGUS)

Intervention Type: OTHER

Other Intervention Names

recombinant human beta-glucuronidase; rh-β-glucuronidase; rhGUS; Reference therapy

Eligibility Criteria

Inclusion Criteria

• Confirmed diagnosis of MPS 7 based on leukocyte or fibroblast glucuronidase enzyme assay or genetic testing.
• Elevated urinary glycosaminoglycan (uGAG) excretion at a minimum of 3-fold over the mean normal for age (at Screening).
• 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.
• Aged 5 - 35 years, inclusive.
• Willing and able to provide written 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.
• 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 Screening 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 Screening, or who have had total hysterectomy.
• Naïve to treatment with UX003.

Exclusion Criteria

• Undergone a successful bone marrow or stem cell transplant or has any degree of detectable chimaerism with donor cells.
• Major surgery within 3 months prior to study entry or planned major surgery during the study that may not allow safe participation in the study.
• 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 Screening or planning to become pregnant (self or partner) at any time during the study.
• Use of any investigational product (drug or device or combination) within 30 days prior to Screening, 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 participation in the study.
• 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
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ultragenyx Pharmaceutical Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul Harmatz, MD

Role: PRINCIPAL_INVESTIGATOR

UCSF Benioff Children's Hospital Oakland

Raymond Wang, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Orange County

Mislen Bauer, MD

Role: PRINCIPAL_INVESTIGATOR

Nicklaus Children's Hospital f/k/a Miami Children's Hospital

Chester Whitley, MD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Locations

Children's Hospital Oakland

Oakland, California, United States

Children's Hospital of Orange County

Orange, California, United States

Miami Children's Hospital

Miami, Florida, United States

University of Minnesota

Minneapolis, Minnesota, United States

Countries

United States

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)

Harmatz P, Whitley CB, Wang RY, Bauer M, Song W, Haller C, Kakkis E. A novel Blind Start study design to investigate vestronidase alfa for mucopolysaccharidosis VII, an ultra-rare genetic disease. Mol Genet Metab. 2018 Apr;123(4):488-494. doi: 10.1016/j.ymgme.2018.02.006. Epub 2018 Feb 12.

Reference Type: RESULT

PMID: 29478819 (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)

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)

Other Identifiers

UX003-CL301

Identifier Type: -

Identifier Source: org_study_id