A Study to Evaluate the Safety, Tolerability and Efficacy of BMN 110 in Subjects With Mucopolysaccharidosis IVA
This study has been completed.
Information provided by (Responsible Party):
First received: April 10, 2009
Last updated: May 28, 2014
Last verified: May 2014
This multicenter, open-label study is designed to assess safety, dose-response using pharmacokinetic (PK) and pharmacodynamic (PD) measures, and clinical efficacy of BMN 110 in subjects between 5 and 18 years of age, diagnosed with Mucopolysaccharidosis IVA (MPS IVA).
MPS IV A
Drug: BMN 110
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Phase 1/2, Multicenter, Open-label, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Efficacy of BMN 110 in Subjects With Mucopolysaccharidosis IVA (Morquio Syndrome)
Primary Outcome Measures:
- Subject Incidence of Treatment Emergent AEs [ Time Frame: Entire Study, through week 84 ] [ Designated as safety issue: Yes ]
The primary objective of the study was to evaluate the safety of weekly infusions of BMN 110 administered in escalating doses to subjects with MPS IVA.
The safety variable incidence of TEAE is summarized.
Secondary Outcome Measures:
- Change From Baseline in 6MWT [ Time Frame: Baseline to Weeks 12, 24, 36, 48, 72 ] [ Designated as safety issue: No ]
Change from baseline in meters in 6-minute Walk Test. As a measure of endurance, a 6-minute walk test (6MWT) was performed according to the American Thoracic Society Guidelines. Patients were instructed to walk as far as possible in 6 minutes.
- Change From Baseline in 3MSCT [ Time Frame: Baseline to Weeks 12, 24, 36, 48, 72 ] [ Designated as safety issue: No ]
Change from baseline in the 3-minute Stair Climb Test. Patients walked up stairs that have a railing, which could be used for support, for 3 minutes, with the number of stairs climbed recorded. The test result was the number of steps climbed per minute.
- Percent Change From Baseline in uKS [ Time Frame: Baseline to Weeks 12, 24, 36, 72 ] [ Designated as safety issue: No ]
Percent Change from baseline in Normalized Urine KS. The percent change was calculated (Week X value - baseline value)/baseline value *100%
- Percent Change From Baseline in MVV [ Time Frame: Baseline to Weeks 12, 24, 36, 72 ] [ Designated as safety issue: No ]
Percent Change from baseline in Maximum Voluntary Ventilation.
- Percent Change From Baseline in FVC [ Time Frame: Baseline to Weeks 12, 24, 36, 72 ] [ Designated as safety issue: No ]
Percent Change from baseline in Forced Vital Capacity.
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||February 2011 (Final data collection date for primary outcome measure)
Experimental: BMN 110
Drug: BMN 110
Subjects will receive a weekly 4- to 5-hour intravenous infusion of BMN 110 in 3 consecutive 12-week dosing intervals, using the following regimen:
- Weeks 1-12: 0.1 mg/kg/week
- Weeks 13-24: 1.0 mg/kg/week
- Weeks 25-36: 2.0 mg/kg/week
Subjects who complete the 36-week Dose-Escalation Period will have the option to continue drug treatment for an additional 36 to 48 weeks. Subjects continuing on treatment after the Dose-Escalation period will receive weekly 4- to 5-hour intravenous infusions of BMN 110 at a dose of 1.0 mg/kg/week.
|Ages Eligible for Study:
||5 Years to 18 Years (Child, Adult)
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Documented history of reduced GALNS activity relative to the normal range of the laboratory performing the assay, or documented result of molecular genetic testing confirming diagnosis of MPS IVA.
- 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.
- Willing to perform all study procedures as physically possible.
- 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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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00884949
|Birmingham, United Kingdom |
|London, United Kingdom |
|Manchester, United Kingdom |
||Celeste Decker, MD
||BioMarin Pharmceutical Inc.
History of Changes
|Other Study ID Numbers:
|Study First Received:
||April 10, 2009
|Results First Received:
||March 13, 2014
||May 28, 2014
||United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee
Keywords provided by BioMarin Pharmaceutical:
Mucopolysaccharidosis IV type A
MPS IV Type A
Morquio A Syndrome
Lysosomal Storage Disorder
enzyme replacement therapy
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on September 27, 2016
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Connective Tissue Diseases