A Double-Blind Study to Evaluate the Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)

MPS IV A Clinical Trial

Official title:

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multinational Clinical Study to Evaluate the Efficacy and Safety of 2.0 mg/kg/Week and 2.0 mg/kg/Every Other Week BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01275066
• Other study ID #: MOR-004
• Secondary ID: 2010-020198-1810
• Status: Completed
• Phase: Phase 3
• First received: January 10, 2011
• Last updated: June 6, 2014
• Start date: February 2011
• Est. completion date: August 2012

Study information

• Verified date: June 2014
• Source: BioMarin Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review BoardUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: Research Ethics CommitteeNetherlands: Medical Ethics Review Committee (METC)Netherlands: Central Committee for Research Involving Human Subjects (CCMO)France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)France: Conseil National de l'Ordre des MédecinsCanada: Health CanadaKorea: Food and Drug AdministrationTaiwan : Food and Drug AdministrationTaiwan: Department of HealthItaly: The Italian Medicines AgencyItaly: Ethics CommitteeArgentina: Ministry of HealthArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaDenmark: Ethics CommitteeDenmark: Danish Health and Medicines AgencyJapan: Institutional Review BoardJapan: Pharmaceuticals and Medical Devices AgencyPortugal: Ethics Committee for Clinical ResearchPortugal: INFARMED - Autoridade Nacional do Medicamento e Produtos de Saúde, I.PBrazil: Ethics CommitteeBrazil: National Health Surveillance AgencyBrazil: National Committee of Ethics in ResearchColombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosColombia: Institutional Review BoardGermany: Ethics CommissionGermany: Federal Institute for Drugs and Medical DevicesQatar: Hamad Medical CorporationSaudi Arabia: Ethics CommitteeSaudi Arabia: Saudi Food and Drug Authority
• Study type: Interventional

Clinical Trial Summary

This Phase 3 study will evaluate the efficacy and safety of 2.0 mg/kg/week BMN 110 and 2.0 mg/kg/every other week BMN 110 in patients with mucopolysaccharidosis IVA (Morquio A Syndrome).

There is currently no standard accepted treatment for MPS IVA other than supportive care. Enzyme replacement therapy (ERT) may be a potential new treatment option for MPS IVA patients. BMN 110 is administered to MPS IVA patients by IV infusion, allowing cellular uptake by the mannose-6-phosphate receptor and transportation to the lysosomes.

This enzyme uptake into the lysosomes is hypothesized to promote increased catabolism of keratan sulfate (KS) in tissue macrophages, hyaline cartilage, other connective tissues, and heart valve, and reduce the progressive accumulation of KS which is responsible for the clinical manifestations of the disorders.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 177
• Est. completion date: August 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years and older

Eligibility

Inclusion Criteria:

• At least 5 years of age.

• Documented clinical diagnosis of MPS IVA based on clinical signs and symptoms of MPS IVA and documented reduced fibroblast or leukocyte GALNS enzyme activity or genetic testing confirming diagnosis of MPS IVA.

• Willing and able to provide written, signed informed consent, or in the case of patients under the age of 18 (or 16 years, depending on the region), 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.

• Must meet the study entrance requirements for the 6-minute walk test.

• Sexually active patients 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.

Exclusion Criteria:

• Previous hematopoietic stem cell transplant (HSCT).

• Previous treatment with BMN 110.

• Has known hypersensitivity to any of the components of BMN 110.

• Major surgery within 3 months prior to study entry or planned major surgery during the 24-week treatment period.

• 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, 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 safety as determined by the Investigator.

• 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• MPS IV A
• Mucopolysaccharidoses
• Mucopolysaccharidosis IV

Intervention

Drug:
• BMN 110 Weekly
BMN 110 Weekly: Intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours once a week.
• Placebo
Intravenous infusion of placebo solution at a volume equivalent to that needed for 2.0 mg/kg dose of BMN 110 administered over a period of approximately 4 hours once a week.
• BMN 110 Every Other Week
BMN 110 Every Other Week: Intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours every other week and infusions of placebo on alternating weeks.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
BioMarin Pharmaceutical

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Colombia,  Denmark,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Portugal,  Qatar,  Saudi Arabia,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Endurance as Measured by the 6-minute Walk Test		Baseline to Week 24	No
Secondary	Change From Baseline in Endurance as Measured by the 3-minute Stair Climb Test		Baseline to Week 24	No
Secondary	Percent Change From Baseline in Urine Keratan Sulfate Normalized for Urine Creatinine		Baseline to Week 24	No

External Links

•   BioMarin Pharmaceutical Inc. website