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 | 14.1 |
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 safety and tolerability of infusions of BMN 110 at a dose of 2.0 mg/kg/week over a 52-week period in MPS IVA patients less than 5 years of age.
For the extension Phase: To evaluate the long-term safety of BMN 110 at a dose of 2.0 mg/kg/week in patients with MPS IVA less than 5 years of age at enrollment. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the ability of 2.0 mg/kg/week BMN 110 to reduce urinary keratan sulfate (KS) levels in MPS IVA patients less than 5 years of age.
• To evaluate the ability of 2.0 mg/kg/week BMN 110 to affect growth velocity in MPS IVA patients less than 5 years of age.
For the extension phase of the study:
• To evaluate the ability of 2.0 mg/kg/week BMN 110 to reduce urinary KS levels in MPS IVA patients less than 5 years of age at enrollment.
• To evaluate the ability of 2.0 mg/kg/week BMN 110 to affect growth velocity in MPS IVA patients less than 5 years of age at enrollment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Less than 5 years of age at the time of the first study-drug infusion.
• 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.
• Written informed consent provided by parent or legally authorized representative after the nature of the study has been explained and prior to any research-related procedures. |
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E.4 | Principal exclusion criteria |
• Previous hematopoietic stem cell transplant (HSCT).
• Previous treatment with BMN 110.
• 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 52-week treatment period.
• 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) |
Evaluate safety and tolerability of infusions of BMN 110 at a dose of 2.0 mg/kg/week over a maximum of 209 week period (52 weeks in the initial clinical phase, and up to 156 doses plus 1 week of assessments in the extension phase) in MPS IVA patients less than 5 years of age (at the time of administration of the first dose of study drug). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Assessed at Screening and each visit |
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E.5.2 | Secondary end point(s) |
* Evaluate the ability of 2.0 mg/kg/week BMN 110 to reduce urinary keratan sulfate (KS) levels in MPS IVA patients less than 5 years of age (at the time of administration of the first dose of study drug)
* Evaluate the ability of 2.0 mg/kg/week BMN 110 to affect growth velocity in MPS IVA patients less than 5 years of age (at the time of administration of the first dose of study drug) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Evaluate the ability of 2.0 mg/kg/week BMN 110 to reduce urinary keratan sulfate (KS) levels in MPS IVA patients less than 5 years of age: Assessed at Baseline, Weeks 2, 4, 8, 13, 26, 39, and 52 and then every 26 weeks up to week 208.
• Evaluate the ability of 2.0 mg/kg/week BMN 110 to affect growth velocity in MPS IVA patients less than 5 years of age: Assessed at Baseline and every 13 weeks up to week 52 and then every 26 weeks up to week 208. |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
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 |
Italy |
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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End of trial is defined as 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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
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 |