Sly SyndromePhase 3NCT02432144
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 study testing UX003 in people with Sly Syndrome and MPS VII, run by Ultragenyx Pharmaceutical Inc at 7 sites in 4 countries.
Trial summary
The primary objective of the study is to evaluate the long-term safety of UX003 in subjects with MPS 7. Read more about this study
- Who is it for?
- Ages 5 years and older
- 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
- 12 participants
- Where
- 7 sitesin 4 countries
- Study dates
- 10 Nov 2015to 14 Jan 2019
- Phase
- Phase 3
- 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 5 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
7 sites in 4 countries.
7 sites in 4 countries
United States4 sites
Baylor College of Medicine
Houston, Texas, 77030
University of Minnesota
Minneapolis, Minnesota, 55455
Children's Hospital Oakland
Oakland, California, 94609
Children's Hospital of Orange County
Orange, California, 92868
Mexico1 site
Centenario Hospital Miguel Hidalgo, Pediatrics
Aguascalientes, 20230
Portugal1 site
Unidade de Doenças Metabólicas - Centro Hospitalar do Porto
Porto, 4050-371
About this study
Official title: A Long-Term Open-Label Treatment and Extension Study of UX003 rhGUS Enzyme Replacement Therapy in Subjects With MPS 7
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.
- 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-glucoronidase, rhGUS, Mepsevii ™, vestronidase alfa
solution for intravenous (IV) infusion
| Study group | Role | What they receive |
|---|---|---|
| UX003 | Experimental | 4 mg/kg UX003 every other week (QOW) Receives: Drug: UX003 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 (1)
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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2015 (estimated)
- Study start10 Nov 2015
- Primary completion14 Jan 2019
- Study completion14 Jan 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 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 Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02432144
- Sponsor's protocol ID
- UX003-CL202
- Other IDs
- 2015-001875-32, 2015
- Status last verified
- Jul 2020
- First submitted
- 22 Apr 2015
- Last updated
- 30 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Expanded access
- Available
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.
PubMed 32063397Montano 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 37415957Tandon 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 at a glance
From the registry record, last updated by the sponsor on 30 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Long-Term Open-Label Treatment and Extension Study of UX003 rhGUS Enzyme Replacement Therapy in Subjects With MPS 7
- ClinicalTrials.gov ID
- NCT02432144
- Acronym / sponsor ID
- UX003-CL202
- Keywords
- MPS 7, Sly Syndrome, MPS VII, Enzyme Replacement Therapy, Rare Disease, Mucopolysaccharidosis Type 7, Lysosomal Storage Disease, Metabolic Disorder
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Ultragenyx Pharmaceutical IncIndustry (pharma, biotech, devices)
- Study start
- 10 Nov 2015 (actual)
- Primary completion
- 14 Jan 2019 (actual)
- Study completion
- 14 Jan 2019 (actual)
- First posted
- 1 May 2015 (estimated)
- Results
- Posted 30 Jul 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 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.
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: UX0034 mg/kg UX003 every other week (QOW) |
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
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-glucoronidase, rhGUS, Mepsevii ™, vestronidase alfasolution for intravenous (IV) infusion | Drug | UX003 |
Primary outcome
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation
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.
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.
1 secondary outcome
Percent Change From Baseline Over Time in Urinary Glycosaminoglycan (uGAG) Excretion (Liquid Chromatography-Tandem Mass Spectrometry, Dermatan Sulfate)
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 and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 32063397Wang 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.
- 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 33874971Tandon 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.
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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 Pharmaceuticals, Inc.
7 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing UX003 in people with Sly Syndrome and MPS VII, run by Ultragenyx Pharmaceutical Inc at 7 sites in 4 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 8 inclusion and 7 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 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Brazil, Mexico, Portugal. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 30 Jul 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?
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation (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.). 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 NCT02432144, 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 Jul 2020.