E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mucopolysaccharidosis Type IV A |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028095 |
E.1.2 | Term | Mucopolysaccharidosis IV |
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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 safety of weekly infusions of BMN 110 administered in escalating doses to subjects with MPS IVA. |
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E.2.2 | Secondary objectives of the trial |
-To determine the pharmacokinetic (PK) parameters of infused BMN 110 in subjects with MPS IVA. -To determine the pharmacodynamic (PD) parameters of infused BMN 110, as measured by change in KS in subjects with MPS IVA. -To evaluate the efficacy of weekly infusions of BMN 110, administered in escalating doses, by monitoring changes in clinical measures of MPS IVA disorder. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Documented history of reduced GALNS activity relative to the normal range of the laboratory performing the assay. -Willing and able to provide written, signed informed consent, or in the case of subjects under the age of 16 years, 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. -Between 5 and 18 years of age, inclusive. -Sexually active subjects 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. Females considered not of childbearing potential include those who have been in menopause at least 2 years, or had tubal ligation at least 1 year prior to Screening, or who have had total hysterectomy. -Willing to perform all study procedures as physically possible. |
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E.4 | Principal exclusion criteria |
-Previous hematopoietic stem cell transplant (HSCT). -Has known hypersensitivity to BMN 110 or its excipients. -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 that would interfere with study participation or safety, including, but not limited to, symptomatic cervical spine instability. -Any condition that, in the view of the Principal Investigator (PI), places the subject 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) |
Safety: -Adverse events -Vital signs -Echocardiograms -Electrocardiograms -Cervical spine (flexion–extension) x-rays -Routine physical examinations, including standard neurologic examination -Standard clinical laboratory tests (serum chemistry, hematology, and urinalysis) -Concomitant medications -Immunogenicity tests
Efficacy: -Plasma KS concentration -Urine KS concentration (normalized to creatinine) -Endurance tests: 6-minute walk test; 3-minute stair climb test (unless clinically contraindicated) -Respiratory function tests: FET; FEV1; FIVC; FVC; MVV; TLC(optional) -Anthropometric measurements (standing height or length, sitting height, knee height, and weight) -MPS Health Assessment Questionnaire
Additional: -PK parameters: AUC(0-infinity); AUC(0-t); Cmax(obs); Tmax(obs); t1/2; CL; Vdz; Vdss -Blood inflammatory biomarkers: TNFα; IL-1β; CRP -Blood biochemical markers of bone and cartilage metabolism: procollagen type IIA N-propeptide; bone-specific alkaline phosphatase; parathyroid hormone; osteocalcin -Thyroid panel |
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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) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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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 | 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 | 3 |
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 | Information not present in EudraCT |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |