Sly SyndromePhase 2NCT02418455
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
A Phase 2 study testing UX003 in people with Sly Syndrome and MPS VII, run by Ultragenyx Pharmaceutical Inc at 5 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 day to 5 years
- Conditions the study is for
- Sly Syndrome, MPS VII, Mucopolysaccharidosis
- What is being tested?
- UX003
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 5 sitesin 3 countries
- Study dates
- 21 Jul 2015to 26 Mar 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 5 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
5 sites in 3 countries.
5 sites in 3 countries
United States3 sites
New York University Langone Medical Center
New York, New York, 10038
University of Utah Hospital
Salt Lake City, Utah, 84132
Children's National Health System
Washington D.C., District of Columbia, 20010
About this study
Official title: An Open-label Study of UX003 rhGUS Enzyme Replacement Therapy in MPS 7 Patients Less Than 5 Years Old
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.
- Being tested
- UX003
- Keywords
- MPS 7, Sly Syndrome, MPS VII, Enzyme Replacement Therapy, Rare Disease, Mucopolysaccharidosis type 7, Lysosomal Storage Disease, Metabolic Disorder
- Medical subject headings
- Mucopolysaccharidosis VII, Mucopolysaccharidoses, Rare Diseases, Lysosomal Storage Diseases, Metabolic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UX003Drug
Also called recombinant human beta-glucuronidase, rhGUS, Mepsevii ™, vestronidase alfa-vjbk
solution for intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| UX003 | Experimental | UX003 4 mg/kg every other week (QOW). Initial treatment period 48 weeks. Continuation period up to 240 weeks. Receives: Drug: UX003 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline (Week 0), Week 48
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.
Measured: 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 (9)
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.
Measured: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132
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.
Measured: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132
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.
Measured: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132
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.
Measured: Baseline, Weeks 12, 24, 36, 48
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.
Measured: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: Baseline, Weeks 12, 24, 48, 96, 144
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.
Measured: Baseline, Weeks 12, 24, 48, 96, 144
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2015 (estimated)
- Study start21 Jul 2015
- Primary completion26 Mar 2019
- Study completion26 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Sly SyndromeStudies of the same condition, open and under way.
- More trials run by Ultragenyx Pharmaceutical IncThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ultragenyx Pharmaceutical Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Ultragenyx Pharmaceutical Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02418455
- Sponsor's protocol ID
- UX003-CL203
- Other IDs
- 2015-000104-26, 2015
- Status last verified
- Oct 2019
- First submitted
- 12 Apr 2015
- Last updated
- 30 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Expanded access
- Available
Publications
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.
PubMed 37415957Lau 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.
PubMed 35331634Qi 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.
PubMed 30467742
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Study of UX003 rhGUS Enzyme Replacement Therapy in MPS 7 Patients Less Than 5 Years Old
- ClinicalTrials.gov ID
- NCT02418455
- Acronym / sponsor ID
- UX003-CL203
- Keywords
- MPS 7, Sly Syndrome, MPS VII, Enzyme Replacement Therapy, Rare Disease, Mucopolysaccharidosis type 7, Lysosomal Storage Disease, Metabolic Disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Ultragenyx Pharmaceutical IncIndustry (pharma, biotech, devices)
- Study start
- 21 Jul 2015 (actual)
- Primary completion
- 26 Mar 2019 (actual)
- Study completion
- 26 Mar 2019 (actual)
- First posted
- 16 Apr 2015 (estimated)
- Results
- Posted 16 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| UX003 | Experimental | Drug: UX003UX003 4 mg/kg every other week (QOW). Initial treatment period 48 weeks. Continuation period up to 240 weeks. |
Who may qualify
- Ages
- 1 day to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UX003Also: recombinant human beta-glucuronidase, rhGUS, Mepsevii ™, vestronidase alfa-vjbksolution for intravenous infusion | Drug | UX003 |
Primary outcome
Percent Change From Baseline in uGAG Excretion (LC-MS/MS-DS) at Week 48
Time frame: Baseline (Week 0), 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
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
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.
9 secondary outcomes
Change From Baseline Over Time in Standing Height
Time frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132
Change From Baseline Over Time in Standing Height Z-Score
Time frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132
Change From Baseline Over Time in Head Circumference
Time frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132
Change From Baseline Over Time in Head Circumference Z-Score
Time frame: Baseline, Weeks 12, 24, 36, 48
Change From Baseline Over Time in Weight
Time frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132
Post-UX003 Growth Velocity (cm/yr) for Participants With Both Historical Pre-UX003 (Within 2 Years) and Post-UX003 Data
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)
Change From Pre-Treatment (Within 2 Years) to Post-Treatment Growth Velocity Z-Score
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)
Change From Baseline Over Time in Liver Measurement
Time frame: Baseline, Weeks 12, 24, 48, 96, 144
Change From Baseline Over Time in Spleen Measurement
Time frame: Baseline, Weeks 12, 24, 48, 96, 144
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37415957Montano 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.
- Derived from this study: PubMed 35331634Lau 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.
- Derived from this study: PubMed 30467742Qi 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Ultragenyx Pharmaceutical Inc
5 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing UX003 in people with Sly Syndrome and MPS VII, run by Ultragenyx Pharmaceutical Inc at 5 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Portugal, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change From Baseline in uGAG Excretion (LC-MS/MS-DS) at Week 48 (time frame: Baseline (Week 0), Week 48). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02418455, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2019.