Clinical trial NCT02418455: 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
Official title: An Open-label Study of UX003 rhGUS Enzyme Replacement Therapy in MPS 7 Patients Less Than 5 Years Old
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Ultragenyx Pharmaceutical Inc
Sponsor class: INDUSTRY
First posted: 2015-04-16
Enrollment: 8
Sex: ALL
Minimum age (years): 1
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percent Change From Baseline in uGAG Excretion (LC-MS/MS-DS) at Week 48
timeFrame: Baseline (Week 0), Week 48
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs
timeFrame: 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:
measure: Change From Baseline Over Time in Standing Height
timeFrame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132
measure: Change From Baseline Over Time in Standing Height Z-Score
timeFrame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132
measure: Change From Baseline Over Time in Head Circumference
timeFrame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132
measure: Change From Baseline Over Time in Head Circumference Z-Score
timeFrame: Baseline, Weeks 12, 24, 36, 48
measure: Change From Baseline Over Time in Weight
timeFrame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132
measure: Post-UX003 Growth Velocity (cm/yr) for Participants With Both Historical Pre-UX003 (Within 2 Years) and Post-UX003 Data
timeFrame: Pre-treatment (based on standing height within 2 years prior to treatment), Post-treatment (based on all standing height data during the study period up to 240 weeks)
measure: Change From Pre-Treatment (Within 2 Years) to Post-Treatment Growth Velocity Z-Score
timeFrame: Pre-treatment (based on standing height within 2 years prior to treatment), Post-treatment (based on all standing height data during the study period up to Week 48)
measure: Change From Baseline Over Time in Liver Measurement
timeFrame: Baseline, Weeks 12, 24, 48, 96, 144
measure: Change From Baseline Over Time in Spleen Measurement
timeFrame: Baseline, Weeks 12, 24, 48, 96, 144
Other outcomes:
Locations:
city: Washington
country: United States
facility: Children's National Health System
state: District of Columbia
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: Porto
country: Portugal
facility: Centro Hospitalar do Porto
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
Study officials:
affiliation: Ultragenyx Pharmaceutical Inc
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.