E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mucopolysaccharidosis type 7 (MPS 7, Sly syndrome) |
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E.1.1.1 | Medical condition in easily understood language |
Mucopolysaccharidosis type 7 (MPS 7, Sly syndrome) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate long-term safety of UX003 in subjects with MPS 7. |
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E.2.2 | Secondary objectives of the trial |
To evaluate long-term efficacy of UX003 in reducing urinary GAG (uGAG) substrate in subjects with MPS 7. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Confirmed diagnosis of MPS 7 based on leukocyte or fibroblast glucuronidase enzyme assay or genetic testing. 2. 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. 3. Willing and able to comply with all study procedures. 4. 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. 5. 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. 6. 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. 7. For UX003 treatment-naïve subjects only, Elevated uGAG excretion at a minimum of 2-fold over normal. 8. For UX003 treatment-naïve subjects only, aged 5 years and older. |
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E.4 | Principal exclusion criteria |
1. 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. 2. Undergone a successful bone marrow or stem cell transplant or has any degree of detectable chimaerism with donor cells. 3. 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. 4. Pregnant or breastfeeding at Baseline or planning to become pregnant (self or partner) at any time during the study. 5. 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. 6. 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. 7. 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety of UX003 as measured by the incidence and frequency of AEs and serious adverse events (SAEs), including clinically significant changes from baseline to scheduled time points in Physical examination findings, Vital signs and weight, ECHO findings, Clinical laboratory evaluations, Concomitant medications, IgG antibodies to rhGUS, Complement C3, C4 and CH50 levels (as indicated). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Assessed up to Week 144. For subjects enrolling from an Ultragenyx-sponsored clinical trial, all AEs will be recorded from the time the subject signs the informed consent and completes the End of Treatment visit in the primary study until 30 days after the last dose of study drug. For subjects who are treatment naïve or who are enrolling from a non-Ultragenyx-sponsored clinical trial, all AEs will be recorded from the time the subject signs the informed consent until 30 days after the last dose of study drug.
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E.5.2 | Secondary end point(s) |
the mean percent change in uGAG excretion. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
First morning void urine samples will be collected every other week up to Week 144. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |