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 | 16.1 |
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 the long-term safety and efficacy of weekly infusions of 2.0 mg/kg of BMN 110 administered in patients with MPS IVA. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the long-term effect of weekly infusions of 2.0 mg/kg of BMN 110 by monitoring changes in biochemical markers of inflammation, and bone and cartilage metabolism, in patients with MPS IVA. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• 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.
• 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 Baseline and be willing to have additional pregnancy tests during the study.
• Must have enrolled in a prior BioMarin sponsored clinical study of BMN 110.
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E.4 | Principal exclusion criteria |
• Pregnant or breastfeeding at Baseline or planning to become pregnant (self or partner) at any time during the study.
• Use of any investigational product (other than BMN 110 in a prior clinical study) or investigational medical device within 30 days prior to Baseline, 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.
• Were enrolled in MOR-004 (patients from MOR-004 may be eligible to participate in a separate, appropriately designed, extension study). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy Variables:
• endurance tests:
─ 6 minute walk (6MW) test
─ 3 minute stair climb (3MSC) test
• urine KS concentration (normalized to creatinine)
• respiratory function tests:
─ forced expiratory time (FET)
─ forced expiratory volume in 1 second (FEV1)
─ forced inspiratory vital capacity (FIVC)
─ forced vital capacity (FVC)
─ maximum voluntary ventilation (MVV)
• anthropometric measurements (standing height, length, sitting height, and weight)
• skeletal radiographs of lumbar spine and lower extremity
• MPS Health Assessment Questionnaire
• EuroQoL EQ-5D-5L
• PRO questionnaires
Safety Variables:
• adverse events (AEs)
• vital signs
• echocardiograms
• electrocardiograms (ECGs)
• cervical spine (flexion–extension) radiographs
• routine physical examinations, including standard neurologic examination and evaluation of presence or absence of corneal clouding
• standard clinical laboratory tests (serum chemistry, hematology, and urinalysis)
• concomitant medications
• immunogenicity tests
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
• At baseline and weekly: adverse events (AEs), vital signs, concomitant medications
• At baseline and every 24 weeks: urine KS concentration, anthropometric measurements, MPS Health Assessment Questionnaire, routine physical examinations, including standard neurologic examination and evaluation of presence or absence of corneal clouding, standard clinical laboratory tests, immunogenicity tests
• At baseline and every 48 weeks: endurance tests (6MW, 3MSC), respiratory function tests (FET, FEV1, FIVC, FVC, MVV), echocardiograms, electrocardiograms (ECGs)
• At baseline and every 72 weeks: skeletal radiographs of lumbar spine and lower extremity, cervical spine (flexion–extension) radiographs
• At or between Week 168 and the end of the study: EuroQoL EQ-5D-5L, PRO questionnaires |
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E.5.2 | Secondary end point(s) |
Exploratory Variables:
• blood inflammatory biomarkers
• biochemical markers of bone and cartilage metabolism |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Exploratory Variables:
• At baseline and every 24 weeks: blood inflammatory biomarkers, and biochemical markers of bone and cartilage metabolism |
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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 | Yes |
E.7.1.3.1 | Other trial type description |
Long-term extension study |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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.8.9.1 | In the Member State concerned years | 4 |
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 | 4 |
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 |