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 |
• Efficacy of UX003 in MPS 7 subjects based on the totality of the clinical data on a per subject basis. No primary endpoint will be declared. (US only)
• Efficacy of UX003 in MPS7 subjects as determined by the percent reduction of uGAG excretion after 24 weeks of treatment relative to the pre-treatment baseline. (EU and rest of World)
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E.2.2 | Secondary objectives of the trial |
• Safety and tolerability following up to 48 weeks of UX003 exposure
• Efficacy of UX003 in MPS 7 subjcts as measured by a multi-domain clinical responder index following 24 weeks of UX003 exposure
• Efficacy following 24 weeks of treatment as determined by the proportion of subjects achieving a positive ICR outcome
• Clinical effects including pulmonary function, walking distance, shoulder flexion, fine motor function, and gross motor function following 24 weeks of UX003 exposure
• Efficacy of UX003 in MPS7 subjects as determined by the percent reduction of uGAG excretion after 24 weeks of treatment relative to the pre-treatment baseline. (US only) |
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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) Elevated uGAG excretion at a minimum of 3-fold over the mean normal for age (at Screening)
3) 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
4) Aged 5 to 35 years, inclusive
5) Willing and able to provide written 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
6) 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
7) 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 not experienced menarche, or have had tubal ligation at least one year prior to Screening, or who have had total hysterectomy
8) Naïve to treatment with UX003 |
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E.4 | Principal exclusion criteria |
1) Undergone a successful bone marrow or stem cell transplant or has any degree of detectable chimaerism with donor cells
2) Major surgery within 3 months prior to study entry or planned major surgery during the study that may not allow safe participation in the study
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 Screening or planning to become pregnant (self or partner) at any time during the study
5) 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
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 participation in the study
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) |
No primary endpoint for US.
For EU and Rest of World, efficacy of UX003 in MPS7 subjects as determined by the percent reduction of uGAG excretion after 24 weeks of treatment relative to the pre-treatment baseline.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
For EU and Rest of World, efficacy (total urinary GAG excretion): Urine samples will be collected every other week up to Week 48, and 2 samples will be collected during the baseline week. |
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E.5.2 | Secondary end point(s) |
• Safety and tolerability following up to 48 weeks of UX003 exposure
• Efficacy of UX003 in MPS 7 subjcts as measured by a multi-domain clinical responder index (MDRI), consisting of 6MWT, FVC, shoulder flexion, visual acuity, BOT-2 fine motor and BOT-2 gross motor, following 24 weeks of UX003 exposure
• Efficacy following 24 weeks of treatment as determined by the proportion of subjects achieving a positive Individualized clinical response (ICR) outcome
• Clinical effects including pulmonary function, walking distance, shoulder flexion, fine motor function, and gross motor function following 24 weeks of UX003 exposure
• Efficacy of UX003 in MPS7 subjects as determined by the percent reduction of uGAG excretion after 24 weeks of treatment relative to the pre-treatment baseline. (US only) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Safety: Assessed up to Week 48. Serious adverse events (SAEs) will be recorded beginning at the time the subject signs the informed consent form (ICF) through 30 days following the last study visit. Non-serious
AEs will be recorded from the time of signing the ICF through the last study visit.
• MDRI: assessed every 8 weeks.
• ICR outcome: assessed every 8 weeks.
• Clinical effects including pulmonary function, walking distance, shoulder flexion, fine motor function, and gross motor function, assessed every 8 weeks.
• For US only - total urinary GAG excretion: Urine samples will be collected every other week up to Week 48, and 2 samples will be collected during the baseline week. |
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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 | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | Yes |
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 | Yes |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |