E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mucopolysaccharidosis Type IVA |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028095 |
E.1.2 | Term | Mucopolysaccharidosis IV |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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 the ability of 2.0 mg/kg/week BMN 110 and 2.0 mg/kg/qow BMN 110 compared with placebo to enhance endurance in patients with MPS IVA, as measured by an increase in the number of meters walked in the 6MW test from baseline to Week 24. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the ability of 2.0 mg/kg/week BMN 110 and 2.0 mg/kg/qow BMN 110 compared with placebo to enhance endurance in patients with MPS IVA, as measured by an increase in the number of stairs climbed per minute in the 3MSC test from baseline to Week 24.
• To evaluate the ability of 2.0 mg/kg/week BMN 110 and 2.0 mg/kg/qow BMN 110 compared with placebo to reduce urine KS levels in patients with MPS IVA, as measured by a decrease in urine KS levels from baseline to Week 24. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• At least 5 years of age.
• Documented clinical diagnosis of MPS IVA based on clinical signs and symptoms of MPS IVA and documented reduced fibroblast or leukocyte GALNS enzyme activity or genetic testing confirming diagnosis of MPS IVA.
• Willing and able to provide written, signed informed consent, or in the case of patients 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.
• Must have an average screening 6MW test distance ≥ 30 and ≤ 325 meters.
• Sexually active patients 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. |
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E.4 | Principal exclusion criteria |
• Previous hematopoietic stem cell transplant (HSCT).
• Previous treatment with BMN 110.
• Has known hypersensitivity to any of the components of BMN 110.
• Major surgery within 3 months prior to study entry or planned major surgery during the 24-week treatment period.
• Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.
• Use of any investigational product or investigational medical device within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
• Concurrent disease or condition, including but not limited to symptomatic cervical spine instability, clinically significant spinal cord compression, or severe cardiac disease that would interfere with study participation or safety as determined by the Investigator.
• Any condition that, in the view of the Investigator, places the patient at high risk of poor treatment compliance or of not completing the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The change from baseline (measured at the Screening visit) in 6MW test distance will be the primary endpoint. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At screening and every 12 weeks |
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E.5.2 | Secondary end point(s) |
3-minute stair climb test; urine keratan sulfate (KS) levels (normalized to creatinine) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
3-minute Stair-Climb Test: Screening and every 12 weeks; urine keratan sulfate (KS) levels (normalized to creatinine): Baseline, week 2, 4, 8, 12, 16, 20, and 24 |
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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 | Yes |
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 | 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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Brazil |
Canada |
Colombia |
Denmark |
France |
Germany |
Italy |
Japan |
Korea, Republic of |
Netherlands |
Norway |
Poland |
Portugal |
Qatar |
Saudi Arabia |
Switzerland |
Taiwan |
United Kingdom |
United States |
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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.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |