Mucopolysaccharidosis Type IV A MedDRA version: 9.1 Level: LLT Classification code 10028095 Term: Mucopolysaccharidosis IV
Conditions
Interventions
Product Name: BMN 110
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: rhGALNS
Other descriptive name: recombinant human N-acetylgalactosamine
Sponsors
BioMarin Pharmaceutical Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: -To evaluate the safety of weekly infusions of BMN 110 administered in escalating doses to subjects with MPS IVA.;Secondary Objective: -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.;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: TNFa; IL-1ß; CRP -Blood biochemical markers of bone and cartilage metabolism: procollagen type IIA N-propeptide; bone-specific alkaline phosphatase; parathyroid hormone; osteocalcin -Thyroid panel | — |
Countries
United Kingdom
Outcome results
None listed