A Study to Evaluate the Safety, Tolerability and Efficacy of BMN 110 in Subjects With Mucopolysaccharidosis IVA
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Purpose
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).
| Condition | Intervention | Phase |
|---|---|---|
|
MPS IV A |
Drug: BMN 110 |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | 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) |
- To evaluate the safety of weekly infusions of BMN 110 based on: vital signs, physical examination, electrocardiogram and echocardiogram tests, cervical spine x-ray, clinical laboratory tests, adverse events, concomitant medications, immunogenicity tests. [ Time Frame: Various, see below for details ] [ Designated as safety issue: Yes ]
Vital signs, adverse events, concomitant medications: Screening,Baseline, Weeks 1 to 72, and 73 to 84 (as needed).
Physical examination: Screening, Baseline, Weeks 12, 24, 36, 48, 60, 72
Electrocardiogram and echocardiogram tests: Screening, Weeks 36, 72
Cervical spine x-ray: Screening, Week 72
Clinical laboratory tests: Screening, Baseline, Weeks 3, 6, 11, 15, 18, 23, 27, 30, 35, 48, 60, 72
Immunogenicity tests: Baseline, Weeks 3, 6, 9, 12, 18, 24, 30, 36, 48, 60, 72
- To determine the pharmacokinetic (PK) parameters of infused BMN 110 in subjects with MPS IVA [ Time Frame: Weeks 1, 12, 24, 36 ] [ Designated as safety issue: No ]
- To determine the pharmacodynamic (PD) parameters of infused BMN 110, as measured by change in KS in subjects with MPS IVA [ Time Frame: Screening, Baseline, Weeks 4, 8, 10, 11, 12, 16, 20, 22, 23, 24, 28, 32, 34, 35, 36, 48, 60, 72 ] [ Designated as safety issue: No ]
- To evaluate the efficacy of weekly infusions of BMN 110 by monitoring changes in clinical measures as measured by on endurance tests (6MWT, 3MSC), respiratory function tests, anthropometric measurements, and MPS Health Assessment Questionnaire [ Time Frame: Various, see below for details ] [ Designated as safety issue: No ]
Endurance tests (6MWT, 3MSC): Baseline, Weeks 6, 12, 18, 24, 30, 36, 48, 72
Respiratory function tests: Baseline, Weeks 12, 24, 36, 48, 72
Anthropometric measurements: Baseline, Weeks 12, 24, 36, 48, 60, 72
MPS Health Assessment Questionnaire: Baseline, Weeks 12, 24, 36, 48, 72
| Enrollment: | 20 |
| Study Start Date: | April 2009 |
| Study Completion Date: | March 2011 |
| Primary Completion Date: | February 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: BMN 110
Within-patient Dose-Escalation
|
Drug: BMN 110
Subjects will receive a weekly 4-hour intravenous infusion of BMN 110 in 3 consecutive 12-week dosing intervals, using the following regimen:
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-hour intravenous infusions of BMN 110 at a dose of 1.0 mg/kg/week. |
Eligibility| Ages Eligible for Study: | 5 Years to 18 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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.
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.
Contacts and Locations| United Kingdom | |
| Birmingham, United Kingdom | |
| London, United Kingdom | |
| Manchester, United Kingdom | |
| Study Director: | Celeste Decker, MD | BioMarin Pharmceutical Inc. |
More Information
Additional Information:
No publications provided
| Responsible Party: | BioMarin Pharmaceutical Inc. |
| ClinicalTrials.gov Identifier: | NCT00884949 History of Changes |
| Other Study ID Numbers: | MOR-002 |
| Study First Received: | April 10, 2009 |
| Last Updated: | July 15, 2011 |
| Health Authority: | United Kingdom: Medicines and Healthcare Products Regulatory Agency United Kingdom: Research Ethics Committee |
Keywords provided by BioMarin Pharmaceutical:
|
Mucopolysaccharidosis IV type A Mucopolysaccharidosis IVA MPS IV Type A MPS IVA Morquio A Syndrome Lysosomal Storage Disorder LSD |
N-acetylgalactosamine-6-sulfatase N-acetylgalactosamine-6-sulfate sulfatase galactose-6-sulfatase GALNS enzyme replacement therapy ERT |
Additional relevant MeSH terms:
|
Mucopolysaccharidoses Mucopolysaccharidosis IV Carbohydrate Metabolism, Inborn Errors Metabolism, Inborn Errors Genetic Diseases, Inborn |
Lysosomal Storage Diseases Mucinoses Connective Tissue Diseases Metabolic Diseases |
ClinicalTrials.gov processed this record on June 17, 2013