Mucopolysaccharidosis Type 7Phase 1/2NCT01856218
An Open-Label Phase 1/2 Study to Assess the Safety, Efficacy and Dose of Study Drug UX003 Recombinant Human Beta-glucuronidase (rhGUS) Enzyme Replacement Therapy in Patients With Mucopolysaccharidosis Type 7 (MPS 7)
A Phase 1/2 study testing UX003 in people with Mucopolysaccharidosis Type 7, run by Ultragenyx Pharmaceutical Inc at 1 site in United Kingdom.
Trial summary
UX003-CL201 is an open-label Phase 1/2 study to assess the safety, efficacy, and dose of UX003 in MPS 7 patients via intravenous (IV) administration every other week (QOW) for 36 weeks with up to an additional 36 weeks from the optional continuation period. Read more about this study
- Who is it for?
- Ages 5 to 30 years
- Conditions the study is for
- Mucopolysaccharidosis Type 7
- What is being tested?
- UX003
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Nov 2013to Jul 2016
- Phase
- Phase 1/2
- 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 5 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Confirmed diagnosis of MPS 7 based on leukocyte or fibroblast glucuronidase enzyme assay or genetic testing confirming diagnosis.
- Elevated urinary glycosaminoglycan (uGAG) excretion at a minimum of 2-fold over normal.
- Between 5 and 30 years of age, inclusive (approximately 2 subjects between the ages of 20-30 years).
- 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.
- Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study.
- Females of childbearing potential must have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have had tubal ligation at least one year prior to Screening, or who have had total hysterectomy.
Who cannot join
- Has undergone a successful bone marrow or stem cell transplant or has 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.
- Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.
- Use of any investigational product (drug or device or combination) 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, that it warrants immediate surgical intervention or other treatment or may not allow safe study participation.
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Manchester Academic Health Science Centre
Manchester
About this study
Official title: An Open-Label Phase 1/2 Study to Assess the Safety, Efficacy and Dose of UX003 rhGUS Enzyme Replacement Therapy in Patients With Mucopolysaccharidosis Type 7 (MPS 7)
UX003-CL201 is an open-label Phase 1/2 study to assess the safety, efficacy, and dose of UX003 in MPS 7 patients via intravenous (IV) administration every other week (QOW) for 36 weeks with up to an additional 36 weeks from the optional continuation period. Up to 5 participants, who are between 5 and 30 years of age inclusive, will be enrolled and treated with UX003.
The initial 12-week treatment period will be followed by a 24-week forced dose titration period to assess the optimal dose. Participants who complete both the initial treatment and forced dose titration periods will continue treatment in a 36- week continuation period.
- Conditions
- Mucopolysaccharidosis Type 7
- Being tested
- UX003
- Keywords
- Mucopolysaccharidosis type 7, MPS 7, Sly syndrome, enzyme replacement therapy, rare disease, lysosomal storage disease, metabolic disorder
- Medical subject headings
- Mucopolysaccharidosis VII, 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
| Study group | Role | What they receive |
|---|---|---|
| UX003 | Experimental | During the initial 14-week treatment period of the study, participants receive 2 mg/kg UX003 every other week (QOW) for 12 weeks. At Week 14, participants continue on UX003 therapy and begin a forced dose titration period for an additional 24 weeks at the dose sequence of 1, 4, and 2 mg/kg UX003 QOW as follows: 1 mg/kg UX003 for 8 weeks beginning on Week 14; then 4 mg/kg UX003 for 8 weeks beginning on Week 22; then 2 mg/kg UX003 for 8 weeks beginning on Week 30. Following the 24 week forced dose titration period, participants who continue on treatment (continuation period) received 2 mg/kg UX003 QOW beginning at Week 38 for up to an additional 36 weeks.
After the first phase of the study, participants who elect to continue drug treatment are transitioned to the long-term extension phase, where they are treated with UX003 at 4 mg/kg beginning at Week 74, for up to an additional 168 weeks. Receives: Drug: UX003 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage Change From Baseline in Urinary Glycosaminoglycan (uGAG) Dermatan Sulfate
Percentage change from baseline in the concentration of uGAGs normalized to the urinary creatinine concentration as measured by liquid chromatography-mass spectrometry/mass spectrometry-dermatan sulfate.
Measured: Baseline, Week 14, Week 22, Week 30, Week 38, Week 72, and end of study (up to Week 132)
Percentage Change From Baseline in uGAG Chondroitin Sulfate
Percentage change from baseline in the concentration of uGAGs normalized to the urinary creatinine concentration as measured by liquid chromatography-mass spectrometry/mass spectrometry-chondroitin sulfate.
Measured: Baseline, Week 14, Week 22, Week 30, Week 38, Week 72, and end of study (up to Week 132)
Number of Participants With Any ≥ 50% Decrease in uGAG
Participants with a ≥ 50% decrease in the concentration of uGAGs normalized to the urinary creatinine concentration as measured by liquid chromatography-mass spectrometry/mass spectrometry-dermatan sulfate or chondroitin sulfate.
Measured: up to Week 132
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, and Study/Treatment Discontinuations
Adverse Event (AE): any untoward medical occurrence in a subject, whether or not considered drug related. 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: Up to 242 weeks + 30 days. SAEs were recorded beginning at the time the subject signed the informed consent form through 30 days following the last study visit. Non-serious AEs were recorded from the time of informed consent through the last study visit.
Secondary outcomes (7)
Acceptable Dose as Determined by Total uGAG Excretion Using a Forced Dose Titration Regimen
The choice of the dose of UX003 QOW for the Long-Term Extension Phase was based on a preliminary efficacy analysis at Week 36 prior to all 3 participants completing the Forced-dose Titration Period of the First Phase of the study.
Measured: Week 36
Change From Baseline at Week 36 in Six-Minute Walk Test (6MWT)
The total distance walked (meters) in a 6-minute period was measured once each test day. The test was conducted using a pre-measured walking course according to administration guidelines established by the American Thoracic Society (ATS 2002). Participants who could not walk could omit this test.
Measured: Baseline, Week 36
Percent of Predicted Normal Distance Walked
The percent of predicted normal distance walked (based on published normative data) in the total distance walked in a six-minute period.
Measured: 36 Weeks
Change From Baseline at Week 36 in the 3-Minute Stair Climb Test (3MSCT)
The number of stairs climbed within a 3-minute period was assessed once each test day using available hospital stairs. Participants who could not climb stairs could omit this test.
Measured: Baseline, Week 36
Change From Baseline at Week 36 in Pulmonary Function Testing (Spirometry)
The following spirometry tests were administered to participants who did not require invasive ventilatory support or have a tracheostomy in accordance with American Thoracic Society/European Respiratory society (ATS/ERS) guidelines: forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), maximum voluntary ventilation in one minute (MVV1). Invasive ventilation is defined as any form of ventilatory support applied with the use of an endotracheal tube.
Measured: Baseline, Week 36
Change From Baseline at Week 36 in Growth Velocity for Height and Weight
Growth velocity (for males ≤18 years and females ≤15) was calculated from anthropometric measurements and compared with pretreatment growth velocity when available. Z-scores and percentiles were calculated using Centers for Disease Control (CDC) growth chart.
Measured: Baseline, Week 36
Change From Baseline at Week 36 in Shoulder Range of Motion (Goniometry)
The maximum passive shoulder range of motion in both flexion and extension will be measured in degrees using a goniometer.
Measured: Baseline, Week 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2013 (estimated)
- Study startNov 2013
- Primary completionJul 2016
- Study completionJul 2016
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 (1)Papers the sponsor has linked to this study.
- Other trials for Mucopolysaccharidosis Type 7Studies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ultragenyx Pharmaceutical Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Simon Jones, MD, Principal investigator, Univeristy of Manchester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01856218
- Sponsor's protocol ID
- UX003-CL201
- Status last verified
- Dec 2018
- First submitted
- 8 May 2013
- Last updated
- 4 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- Expanded access
- Available
Publications
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.
PubMed 30467742
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Phase 1/2 Study to Assess the Safety, Efficacy and Dose of UX003 rhGUS Enzyme Replacement Therapy in Patients With Mucopolysaccharidosis Type 7 (MPS 7)
- ClinicalTrials.gov ID
- NCT01856218
- Acronym / sponsor ID
- UX003-CL201
- Conditions
- Mucopolysaccharidosis Type 7
- Keywords
- Mucopolysaccharidosis type 7, MPS 7, Sly syndrome, enzyme replacement therapy, rare disease, lysosomal storage disease, metabolic disorder
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Ultragenyx Pharmaceutical IncIndustry (pharma, biotech, devices)
- Study start
- Nov 2013
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 17 May 2013 (estimated)
- Results
- Posted 5 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
UX003-CL201 is an open-label Phase 1/2 study to assess the safety, efficacy, and dose of UX003 in MPS 7 patients via intravenous (IV) administration every other week (QOW) for 36 weeks with up to an additional 36 weeks from the optional continuation period. Up to 5 participants, who are between 5 and 30 years of age inclusive, will be enrolled and treated with UX003.
The initial 12-week treatment period will be followed by a 24-week forced dose titration period to assess the optimal dose. Participants who complete both the initial treatment and forced dose titration periods will continue treatment in a 36- week continuation period.
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: UX003During the initial 14-week treatment period of the study, participants receive 2 mg/kg UX003 every other week (QOW) for 12 weeks. At Week 14, participants continue on UX003 therapy and begin a forced dose titration period for an additional 24 weeks at the dose sequence of 1, 4, and 2 mg/kg UX003 QOW as follows: 1 mg/kg UX003 for 8 weeks beginning on Week 14; then 4 mg/kg UX003 for 8 weeks beginning on Week 22; then 2 mg/kg UX003 for 8 weeks beginning on Week 30. Following the 24 week forced dose titration period, participants who continue on treatment (continuation period) received 2 mg/kg UX003 QOW beginning at Week 38 for up to an additional 36 weeks. After the first phase of the study, participants who elect to continue drug treatment are transitioned to the long-term extension phase, where they are treated with UX003 at 4 mg/kg beginning at Week 74, for up to an additional 168 weeks. |
Who may qualify
- Ages
- 5 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Confirmed diagnosis of MPS 7 based on leukocyte or fibroblast glucuronidase enzyme assay or genetic testing confirming diagnosis.
- Elevated urinary glycosaminoglycan (uGAG) excretion at a minimum of 2-fold over normal.
- Between 5 and 30 years of age, inclusive (approximately 2 subjects between the ages of 20-30 years).
- 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.
- Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study.
Key exclusion criteria (6 listed)
- Has undergone a successful bone marrow or stem cell transplant or has 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.
- Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.
- Use of any investigational product (drug or device or combination) 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, that it warrants immediate surgical intervention or other treatment or may not allow safe study participation.
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 |
|---|---|---|
| UX003 | Drug | UX003 |
Primary outcome
Percentage Change From Baseline in Urinary Glycosaminoglycan (uGAG) Dermatan Sulfate
Time frame: Baseline, Week 14, Week 22, Week 30, Week 38, Week 72, and end of study (up to Week 132)
Percentage change from baseline in the concentration of uGAGs normalized to the urinary creatinine concentration as measured by liquid chromatography-mass spectrometry/mass spectrometry-dermatan sulfate.
Percentage Change From Baseline in uGAG Chondroitin Sulfate
Time frame: Baseline, Week 14, Week 22, Week 30, Week 38, Week 72, and end of study (up to Week 132)
Percentage change from baseline in the concentration of uGAGs normalized to the urinary creatinine concentration as measured by liquid chromatography-mass spectrometry/mass spectrometry-chondroitin sulfate.
Number of Participants With Any ≥ 50% Decrease in uGAG
Time frame: up to Week 132
Participants with a ≥ 50% decrease in the concentration of uGAGs normalized to the urinary creatinine concentration as measured by liquid chromatography-mass spectrometry/mass spectrometry-dermatan sulfate or chondroitin sulfate.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Deaths, and Study/Treatment Discontinuations
Time frame: Up to 242 weeks + 30 days. SAEs were recorded beginning at the time the subject signed the informed consent form through 30 days following the last study visit. Non-serious AEs were recorded from the time of informed consent through the last study visit.
Adverse Event (AE): any untoward medical occurrence in a subject, whether or not considered drug related. 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.
7 secondary outcomes
Acceptable Dose as Determined by Total uGAG Excretion Using a Forced Dose Titration Regimen
Time frame: Week 36
Change From Baseline at Week 36 in Six-Minute Walk Test (6MWT)
Time frame: Baseline, Week 36
Percent of Predicted Normal Distance Walked
Time frame: 36 Weeks
Change From Baseline at Week 36 in the 3-Minute Stair Climb Test (3MSCT)
Time frame: Baseline, Week 36
Change From Baseline at Week 36 in Pulmonary Function Testing (Spirometry)
Time frame: Baseline, Week 36
Change From Baseline at Week 36 in Growth Velocity for Height and Weight
Time frame: Baseline, Week 36
Change From Baseline at Week 36 in Shoulder Range of Motion (Goniometry)
Time frame: Baseline, Week 36
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Related trials for Mucopolysaccharidosis Type 7
RecruitingObservational study
Mucopolysaccharidosis VII Disease Monitoring Program
Mucopolysaccharidosis VII, MPS VII
Active, not recruitingObservational study
Early Check: Expanded Screening in Newborns
Spinal Muscular Atrophy, Fragile X Syndrome
RecruitingObservational study
Registry of Patients Diagnosed With Lysosomal Storage Diseases
Mucopolysaccharidosis I, Mucopolysaccharidosis II
RecruitingPhase 1
PEARL (PrEnAtal Enzyme Replacement Therapy for Lysosomal Storage Disorders)
MPS I, MPS II
Active, not recruitingPhase 2
MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
Mucopolysaccharidosis Disorders, Hurler Syndrome
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.
Simon Jones, MD principal investigator
Univeristy of Manchester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing UX003 in people with Mucopolysaccharidosis Type 7, run by Ultragenyx Pharmaceutical Inc at 1 site in United Kingdom.
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 6 inclusion and 6 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 4 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 5 Jan 2018). 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?
Percentage Change From Baseline in Urinary Glycosaminoglycan (uGAG) Dermatan Sulfate (time frame: Baseline, Week 14, Week 22, Week 30, Week 38, Week 72, and end of study (up to Week 132)). The study lists 4 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 NCT01856218, which also lists 1 linked publication.
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 4 Jan 2019.