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 the long-term safety and efficacy of BMN 110 administration at 2.0 mg/kg/qw and 2.0 mg/kg/qow in patients with MPS IVA. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the long-term effect of BMN 110 administration at 2.0 mg/kg/qw and 2.0 mg/kg/qow on 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 |
• Must have completed MOR-004.
• Is willing and able to provide written, signed informed consent. Or, in the case of patients under the age of 18 (or other age as defined by regional law or regulation), provide written assent (if required) and have written informed consent, signed by a legally authorized representative, after the nature of the study has been explained, and prior to performance of research-related procedures.
• If sexually active, must be willing to use an acceptable method of contraception while participating in the study.
• If female, of childbearing potential, must have a negative pregnancy test at Baseline and be willing to have additional pregnancy tests done during the study. |
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E.4 | Principal exclusion criteria |
• Is pregnant or breastfeeding, at Baseline, or planning to become pregnant (self or partner) at any time during the study.
• Has used any investigational product (other than BMN 110 in MOR-004), or investigational medical device, within 30 days prior to Baseline; or is required to use any investigational agent prior to completion of all scheduled study assessments.
• Was enrolled in a previous BMN 110 study, other than MOR-004.
• Has a 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 pose a safety risk, as determined by the Investigator.
• Has 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) |
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 X-rays of lumbar spine and lower extremity
• MPS Health Assessment Questionnaire
• audiometry examinations
Safety Variables:
• adverse events (AEs)
• standard clinical laboratory tests (serum chemistry, hematology, and urinalysis)
• vital signs
• echocardiograms
• electrocardiograms (ECGs)
• routine physical examinations (including standard neurologic examination)
• concomitant medications
• immunogenicity tests
• cervical spine (flexion–extension) X-rays |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
• 6MW test, 3MSC test: baseline, wk 12, every 24 wks in Part 1, every 48 wks in Part 2
• respiratory function tests: baseline, every 24 wks in Part 1, every 48 wks in Part 2
• anthropometric measurements, MPS Health Assessment Questionnaire, audiometry examinations: baseline, every 24 wks in Part 1 and Part 2
• adverse events, vital signs, concomitant medications: baseline, weekly in Part 1, weekly or every other week in Part 2
• echocardiograms, electrocardiograms: baseline, every 48 wks in Part 2
• routine physical examinations, immunogenicity tests, standard clinical laboratory tests, urine KS concentration: baseline, every 12 wks in Part 1, every 24 wks in Part 2
• x-rays of cervical spine, lumbar spine and lower extremity: baseline, every 72 wks in Part 2 |
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E.5.2 | Secondary end point(s) |
Exploratory Variables:
• blood inflammatory biomarkers
• blood 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:
• blood inflammatory biomarkers, and blood biochemical markers of bone and cartilage metabolism: baseline, every 24 wks in Part 1 and Part 2
•To evaluate patient perception of impairment and improvement in patients with MPS IVA.
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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 | 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 | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
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 | 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 |