A Study of UX003 Recombinant Human Beta-Glucuronidase (rhGUS) Enzyme Replacement Therapy in Subjects With Mucopolysaccharidosis Type 7, Sly Syndrome (MPS 7)
Primary Purpose
Sly Syndrome, MPS VII, Mucopolysaccharidosis
Status
Completed
Phase
Phase 3
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.
- 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.
Sites / Locations
- Children's Hospital Oakland
- Children's Hospital of Orange County
- University of Minnesota
- Baylor College of Medicine
- Hospital Infantil Candido Fontoura Sao Paulo
- Centenario Hospital Miguel Hidalgo, Pediatrics
- Unidade de Doenças Metabólicas - Centro Hospitalar do Porto
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
UX003
Arm Description
4 mg/kg UX003 every other week (QOW)
Outcomes
Primary Outcome Measures
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation
An adverse event (AE) is defined as any untoward medical occurrence, whether or not considered drug related. A serious AE is an AE 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; or is an important medical event. AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), Grade 5 (death). TEAEs were defined as reported AEs with onset during the treatment.
Secondary Outcome Measures
Percent Change From Baseline Over Time in Urinary Glycosaminoglycan (uGAG) Excretion (Liquid Chromatography-Tandem Mass Spectrometry, Dermatan Sulfate)
First morning void urine was evaluated for uGAG concentration and normalized to urinary creatinine concentration.
Full Information
NCT ID
NCT02432144
First Posted
April 22, 2015
Last Updated
July 16, 2020
Sponsor
Ultragenyx Pharmaceutical Inc
1. Study Identification
Unique Protocol Identification Number
NCT02432144
Brief Title
A Study of UX003 Recombinant Human Beta-Glucuronidase (rhGUS) Enzyme Replacement Therapy in Subjects With Mucopolysaccharidosis Type 7, Sly Syndrome (MPS 7)
Official Title
A Long-Term Open-Label Treatment and Extension Study of UX003 rhGUS Enzyme Replacement Therapy in Subjects With MPS 7
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
November 10, 2015 (Actual)
Primary Completion Date
January 14, 2019 (Actual)
Study Completion Date
January 14, 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 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.
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 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
UX003
Arm Type
Experimental
Arm Description
4 mg/kg UX003 every other week (QOW)
Intervention Type
Drug
Intervention Name(s)
UX003
Other Intervention Name(s)
recombinant human beta-glucoronidase, rhGUS, Mepsevii ™, vestronidase alfa, vestronidase alfa-vjbk
Intervention Description
solution for intravenous (IV) infusion
Primary Outcome Measure Information:
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation
Description
An adverse event (AE) is defined as any untoward medical occurrence, whether or not considered drug related. A serious AE is an AE 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; or is an important medical event. AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), Grade 5 (death). TEAEs were defined as reported AEs with onset during the treatment.
Time Frame
From first dose of study drug until 30 days after the last dose of study drug. Mean duration of UX003 treatment was 100.5 weeks.
Secondary Outcome Measure Information:
Title
Percent Change From Baseline Over Time in Urinary Glycosaminoglycan (uGAG) Excretion (Liquid Chromatography-Tandem Mass Spectrometry, Dermatan Sulfate)
Description
First morning void urine was evaluated for uGAG concentration and normalized to urinary creatinine concentration.
Time Frame
Baseline (prior to the first dose of study drug in UX003-CL301), Weeks 0, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144
10. Eligibility
Sex
All
Minimum 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.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Ultragenyx Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Children's Hospital Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
Children's Hospital of Orange County
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Hospital Infantil Candido Fontoura Sao Paulo
City
Sao Paulo
Country
Brazil
Facility Name
Centenario Hospital Miguel Hidalgo, Pediatrics
City
Aguascalientes
ZIP/Postal Code
20230
Country
Mexico
Facility Name
Unidade de Doenças Metabólicas - Centro Hospitalar do Porto
City
Porto
ZIP/Postal Code
4050-371
Country
Portugal
12. IPD Sharing Statement
Citations:
PubMed Identifier
32063397
Citation
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. Erratum In: Mol Genet Metab. 2020 Sep - Oct;131(1-2):285.
Results Reference
result
PubMed Identifier
33874971
Citation
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.
Results Reference
derived
Learn more about this trial
A Study of UX003 Recombinant Human Beta-Glucuronidase (rhGUS) Enzyme Replacement Therapy in Subjects With Mucopolysaccharidosis Type 7, Sly Syndrome (MPS 7)
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