Back to resultsStudy 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
Primary Purpose
Sly Syndrome, MPS VII, Mucopolysaccharidosis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
UX003
Sponsored by
About this trial
This is an interventional treatment trial for Sly Syndrome focused on measuring MPS 7, Sly Syndrome, MPS VII, Enzyme Replacement Therapy, Rare Disease, Mucopolysaccharidosis type 7, Lysosomal Storage Disease, Metabolic Disorder
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
- Children's National Health System
- New York University Langone Medical Center
- University of Utah Hospital
- Centro Hospitalar do Porto
- Hospital Universitario Virgen Del Rocio
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
UX003
Arm Description
UX003 4 mg/kg every other week (QOW). Initial treatment period 48 weeks. Continuation period up to 240 weeks.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Change From Baseline Over Time in Standing Height
For all participants (including the participant previously treated with UX003 under an eIND), the last non-missing study assessment prior to the first dose in this study was used as baseline.
Change From Baseline Over Time in Standing Height Z-Score
The Z-score indicates the number of standard deviations away from a reference population (from the CDC growth charts) in the same age range and with the same sex. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z-scores indicate a better outcome.
For all participants (including the participant previously treated with UX003 under an eIND), the last non-missing study assessment prior to the first dose in this study was used as baseline.
Change From Baseline Over Time in Head Circumference
For all participants (including the participant previously treated with UX003 under an eIND), the last non-missing study assessment prior to the first dose in this study was used as baseline.
Change From Baseline Over Time in Head Circumference Z-Score
The Z-score indicates the number of standard deviations away from a reference population (from the CDC growth charts) in the same age range and with the same sex. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z-scores indicate a better outcome.
For all participants (including the participant previously treated with UX003 under an eIND), the last non-missing study assessment prior to the first dose in this study was used as baseline.
Change From Baseline Over Time in Weight
For all participants (including the participant previously treated with UX003 under an eIND), the last non-missing study assessment prior to the first dose in this study was used as baseline.
Post-UX003 Growth Velocity (cm/yr) for Participants With Both Historical Pre-UX003 (Within 2 Years) and Post-UX003 Data
The growth velocity for pre-treatment is based on standing height within 2 years prior to treatment. The growth velocity for post-treatment is based on all standing height data during the study period. For the participant previously treated with UX003 under an eIND, the growth velocity was calculated for pre initial UX003 treatment and post initial UX003 treatment.
Change From Pre-Treatment (Within 2 Years) to Post-Treatment Growth Velocity Z-Score
The Z-score indicates the number of standard deviations away from a reference population (based on Tanner's standard [Tanner et al. 1985]) in the same age range and with the same sex. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z-scores indicate a better outcome.
The growth velocity for pre-treatment is based on standing height within 2 years prior to treatment. The growth velocity for post-treatment is based on all standing height data during the study period. For the participant previously treated with UX003 under an eIND, the growth velocity was calculated for pre initial UX003 treatment and post initial UX003 treatment.
Change From Baseline Over Time in Liver Measurement
For all participants (including the participant previously treated with UX003 under an eIND), the last non-missing study assessment prior to the first dose in this study was used as baseline.
Change From Baseline Over Time in Spleen Measurement
For all participants (including the participant previously treated with UX003 under an eIND), the last non-missing study assessment prior to the first dose in this study was used as baseline.
Full Information
NCT ID
NCT02418455
First Posted
April 12, 2015
Last Updated
October 15, 2019
Sponsor
Ultragenyx Pharmaceutical Inc
1. Study Identification
Unique Protocol Identification Number
NCT02418455
Brief Title
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
2. Study Status
Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
July 21, 2015 (Actual)
Primary Completion Date
March 26, 2019 (Actual)
Study Completion Date
March 26, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ultragenyx Pharmaceutical Inc
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
UX003
Arm Type
Experimental
Arm Description
UX003 4 mg/kg every other week (QOW). Initial treatment period 48 weeks. Continuation period up to 240 weeks.
Intervention Type
Drug
Intervention Name(s)
UX003
Other Intervention Name(s)
recombinant human beta-glucuronidase, rhGUS, Mepsevii ™, vestronidase alfa-vjbk, vestronidase alfa
Intervention Description
solution for intravenous infusion
Primary Outcome Measure Information:
Title
Percent Change From Baseline in uGAG Excretion (LC-MS/MS-DS) at Week 48
Description
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.
Time Frame
Baseline (Week 0), Week 48
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs
Description
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.
Time Frame
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 Outcome Measure Information:
Title
Change From Baseline Over Time in Standing Height
Description
For all participants (including the participant previously treated with UX003 under an eIND), the last non-missing study assessment prior to the first dose in this study was used as baseline.
Time Frame
Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132
Title
Change From Baseline Over Time in Standing Height Z-Score
Description
The Z-score indicates the number of standard deviations away from a reference population (from the CDC growth charts) in the same age range and with the same sex. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z-scores indicate a better outcome.
For all participants (including the participant previously treated with UX003 under an eIND), the last non-missing study assessment prior to the first dose in this study was used as baseline.
Time Frame
Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132
Title
Change From Baseline Over Time in Head Circumference
Description
For all participants (including the participant previously treated with UX003 under an eIND), the last non-missing study assessment prior to the first dose in this study was used as baseline.
Time Frame
Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132
Title
Change From Baseline Over Time in Head Circumference Z-Score
Description
The Z-score indicates the number of standard deviations away from a reference population (from the CDC growth charts) in the same age range and with the same sex. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z-scores indicate a better outcome.
For all participants (including the participant previously treated with UX003 under an eIND), the last non-missing study assessment prior to the first dose in this study was used as baseline.
Time Frame
Baseline, Weeks 12, 24, 36, 48
Title
Change From Baseline Over Time in Weight
Description
For all participants (including the participant previously treated with UX003 under an eIND), the last non-missing study assessment prior to the first dose in this study was used as baseline.
Time Frame
Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132
Title
Post-UX003 Growth Velocity (cm/yr) for Participants With Both Historical Pre-UX003 (Within 2 Years) and Post-UX003 Data
Description
The growth velocity for pre-treatment is based on standing height within 2 years prior to treatment. The growth velocity for post-treatment is based on all standing height data during the study period. For the participant previously treated with UX003 under an eIND, the growth velocity was calculated for pre initial UX003 treatment and post initial UX003 treatment.
Time Frame
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)
Title
Change From Pre-Treatment (Within 2 Years) to Post-Treatment Growth Velocity Z-Score
Description
The Z-score indicates the number of standard deviations away from a reference population (based on Tanner's standard [Tanner et al. 1985]) in the same age range and with the same sex. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z-scores indicate a better outcome.
The growth velocity for pre-treatment is based on standing height within 2 years prior to treatment. The growth velocity for post-treatment is based on all standing height data during the study period. For the participant previously treated with UX003 under an eIND, the growth velocity was calculated for pre initial UX003 treatment and post initial UX003 treatment.
Time Frame
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)
Title
Change From Baseline Over Time in Liver Measurement
Description
For all participants (including the participant previously treated with UX003 under an eIND), the last non-missing study assessment prior to the first dose in this study was used as baseline.
Time Frame
Baseline, Weeks 12, 24, 48, 96, 144
Title
Change From Baseline Over Time in Spleen Measurement
Description
For all participants (including the participant previously treated with UX003 under an eIND), the last non-missing study assessment prior to the first dose in this study was used as baseline.
Time Frame
Baseline, Weeks 12, 24, 48, 96, 144
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Day
Maximum Age & Unit of Time
5 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Ultragenyx Pharmaceutical Inc
Official's Role
Study Director
Facility Information:
Facility Name
Children's National Health System
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
New York University Langone Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10038
Country
United States
Facility Name
University of Utah Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Centro Hospitalar do Porto
City
Porto
ZIP/Postal Code
4099-345
Country
Portugal
Facility Name
Hospital Universitario Virgen Del Rocio
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
35331634
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.
Results Reference
derived
PubMed Identifier
30467742
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. Erratum In: Clin Pharmacokinet. 2018 Dec 4;:
Results Reference
derived
Learn more about this trial
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
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