CompletedNCT02432144Updated Jul 30, 2020Results posted

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

A Phase 3 interventional study of UX003 in Sly Syndrome, MPS VII and Mucopolysaccharidosis, sponsored by Ultragenyx Pharmaceutical Inc. Completed at 7 sites in 4 countries. Open to participants aged 5 Years and older. Per ClinicalTrials.gov, last updated 2020-07-30.

Sponsored by Ultragenyx Pharmaceutical Inc · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 12
Allocation: Not applicable
Ages: 5 Years and older
Sex: All

Study summary

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

Read the 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 studied

Sly Syndrome
MPS VII
Mucopolysaccharidosis
Mucopolysaccharidosis VII

Browse trials for

Keywords

MPS 7
Sly Syndrome
MPS VII
Enzyme Replacement Therapy
Rare Disease
Mucopolysaccharidosis Type 7
Lysosomal Storage Disease
Metabolic Disorder

In context

Mucopolysaccharidoses

145 studies on the registry are indexed under Mucopolysaccharidoses; 11 are open to participants now.

This study's enrollment of 12 is below the median of 15 across 80 interventional studies indexed under Mucopolysaccharidoses.

Browse Mucopolysaccharidoses studies →

Lead sponsor

Ultragenyx Pharmaceutical Inc is the lead sponsor of 63 studies on the registry; 8 are open to participants now.

Of its 13 completed or terminated interventional studies of FDA-regulated products, 11 (85%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 5 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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

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.

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 12 participants (actual)

Study arms

Experimental
UX003
4 mg/kg UX003 every other week (QOW)
Drug: UX003

Interventions

DrugUX003
solution for intravenous (IV) infusion
Also known as: recombinant human beta-glucoronidase, rhGUS, Mepsevii ™, vestronidase alfa, vestronidase alfa-vjbk

What researchers measure

Primary outcomes

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.
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 outcomes

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.
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

Results

Posted Jul 30, 2019

Participant flow

Participants with mucopolysaccharidosis VII (MPS 7) who were UX003 treatment-naïve or previously enrolled and treated in a prior clinical study of UX003 could enroll into this treatment and extension study provided all eligibility criteria had been met for a given participant.

Participant flow — Overall Study
Milestone	UX003
Started	12
Completed	11
Not completed	1
Withdrew: Participant non-compliance	1

Outcome measures

PrimaryNumber 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.

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.
Reported as:: Count of participants · Participants

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation
Participants	UX003
TEAEs	12
Serious TEAEs	4
Treatment-Related TEAEs	9
Treatment-Related Serious TEAEs	1
Grade 3 or 4 TEAEs	3
TEAEs Leading to Treatment Discontinuation	0
TEAEs Leading to Study Discontinuation	0
TEAEs Leading to Death	0

SecondaryPercent 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.

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
Reported as:: Mean · percentage change in uGAG excretion

Percent Change From Baseline Over Time in Urinary Glycosaminoglycan (uGAG) Excretion (Liquid Chromatography-Tandem Mass Spectrometry, Dermatan Sulfate)
percentage change in uGAG excretion	UX003
Week 0	-62.19 ± 16.133
Week 12	-67.31 ± 13.953
Week 24	-64.03 ± 14.669
Week 36	-60.58 ± 23.552
Week 48	-57.04 ± 23.611
Week 60	-72.25 ± 18.609
Week 72	-78.52 ± 10.367
Week 84	-80.89 ± 10.023
Week 96	-82.39 ± 6.011
Week 108	-82.19 ± 6.551
Week 120	-88.74 ± 4.023
Week 132	-89.22 ± 3.662
Week 144	-91.62 ± 1.827

Statistical analysis

UX003 · GEE model · p = < 0.0001 (P-values are from generalized estimating equation (GEE) model including baseline value and visit (in this study) as a categorical variable. The covariance structure within subjects is assumed to be exchangeable.) · Ls mean: -62.28 · 95% CI -71.98 to -52.59
UX003 · GEE model · p = < 0.0001 (P-values are from a GEE model including baseline value and visit (in this study) as a categorical variable. The covariance structure within subjects is assumed to be exchangeable.) · Ls mean: -67.18 · 95% CI -73.49 to -60.86
UX003 · GEE model · p = < 0.0001 (P-values are from a GEE model including baseline value and visit (in this study) as a categorical variable. The covariance structure within subjects is assumed to be exchangeable.) · Ls mean: -64.12 · 95% CI -71.99 to -56.24
UX003 · GEE model · p = < 0.0001 (P-values are from a GEE model including baseline value and visit (in this study) as a categorical variable. The covariance structure within subjects is assumed to be exchangeable.) · Ls mean: -60.80 · 95% CI -72.54 to -49.06
UX003 · GEE model · p = < 0.0001 (P-values are from a GEE model including baseline value and visit (in this study) as a categorical variable. The covariance structure within subjects is assumed to be exchangeable.) · Ls mean: -57.85 · 95% CI -71.87 to -43.82

Adverse events

Collected over 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.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
UX003	0/12 (0%)	4/12 (33.3%)	12/12 (100%)

Most frequent serious events

Most frequent serious events
Event	UX003
GastroenteritisInfections and infestations	1/12
Head InjuryInjury, poisoning and procedural complications	1/12
HeadacheNervous system disorders	1/12
Asthmatic CrisisRespiratory, thoracic and mediastinal disorders	1/12
BronchospasmRespiratory, thoracic and mediastinal disorders	1/12
Interstitial Lung DiseaseRespiratory, thoracic and mediastinal disorders	1/12
UrticariaSkin and subcutaneous tissue disorders	1/12

Most frequent other events

Showing 10 of 103

Most frequent other events
Event	UX003
Upper Respiratory Tract InfectionInfections and infestations	7/12
Infusion Site ExtravasationGeneral disorders	5/12
VomitingGastrointestinal disorders	4/12
CoughRespiratory, thoracic and mediastinal disorders	4/12
UrticariaSkin and subcutaneous tissue disorders	4/12
Gastrooesophageal Reflux DiseaseGastrointestinal disorders	3/12
RhinitisInfections and infestations	3/12
Nasal CongestionRespiratory, thoracic and mediastinal disorders	3/12
Ear PainEar and labyrinth disorders	2/12
Conjunctivitis AllergicEye disorders	2/12

Baseline characteristics

Age, Continuous
Age, Continuous(years)	UX003
Mean	16.56 ± 5.466

Sex: Female, Male
Sex: Female, Male(Participants)	UX003
Female	8
Male	4

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	UX003
Hispanic or Latino	6
Not Hispanic or Latino	6
Unknown or Not Reported	0

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	UX003
White	9
Other, Not Specified	3

Urinary Glycosaminoglycans (uGAG)
Urinary Glycosaminoglycans (uGAG)(g GAG/g creatinine)	UX003
Mean	1.54848 ± 0.413237

Study locations

7 sites

Children's Hospital Oakland
Oakland, California 94609, United States
Children's Hospital of Orange County
Orange, California 92868, United States
University of Minnesota
Minneapolis, Minnesota 55455, United States
Baylor College of Medicine
Houston, Texas 77030, United States
Hospital Infantil Candido Fontoura Sao Paulo
Sao Paulo, Brazil
Centenario Hospital Miguel Hidalgo, Pediatrics
Aguascalientes, 20230, Mexico
Unidade de Doenças Metabólicas - Centro Hospitalar do Porto
Porto, 4050-371, Portugal

References and documents

Publications

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. doi: 10.1016/j.ymgme.2020.08.001. PubMed 32063397 ↗
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. PubMed 33874971 ↗

Study documents

Study protocol · Jul 28, 2016
Statistical analysis plan · Mar 8, 2016

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jul 30, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02432144
Lead sponsor: Ultragenyx Pharmaceutical Inc
Responsible party: Sponsor
First posted: May 1, 2015
Start date: Nov 10, 2015
Primary completion: Jan 14, 2019
Completion: Jan 14, 2019
Results posted: Jul 30, 2019
Last update: Jul 30, 2020

Study contacts

Medical Director

study director · Ultragenyx Pharmaceuticals, Inc.

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jul 2020. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Mucopolysaccharidoses→

Other studies from this sponsor

Ultragenyx Pharmaceutical Inc

Start the discussion