Clinical trial NCT01275066: A Double-Blind Study to Evaluate the Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: MPS IV A
Keywords: Mucopolysaccharidosis IV type A
MPS IV Type A
Mucopolysaccharidosis IVA
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
Lead sponsor: BioMarin Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2011-01-12
Enrollment: 177
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Endurance as Measured by the 6-minute Walk Test
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Change From Baseline in Endurance as Measured by the 3-minute Stair Climb Test
timeFrame: Baseline to Week 24
measure: Percent Change From Baseline in Urine Keratan Sulfate Normalized for Urine Creatinine
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: Oakland
country: United States
state: California
city: Wilmington
country: United States
state: Delaware
city: Washington
country: United States
state: District of Columbia
city: Chicago
country: United States
state: Illinois
city: New York
country: United States
state: New York
city: Seattle
country: United States
state: Washington
city: Cordoba
country: Argentina
city: Campina Grande
country: Brazil
city: Porto Alegre
country: Brazil
city: Montreal
country: Canada
city: Sherbrooke
country: Canada
city: Toronto
country: Canada
city: Bogota
country: Colombia
city: Copenhagen
country: Denmark
city: Lyon
country: France
city: Paris
country: France
city: Mainz
country: Germany
city: Monza
country: Italy
city: Tokyo
country: Japan
city: Seoul
country: Korea, Republic of
city: Amsterdam
country: Netherlands
city: Coimbra
country: Portugal
city: Doha
country: Qatar
city: Riyadh
country: Saudi Arabia
city: Taipei
country: Taiwan
city: Birmingham
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
Study officials:
affiliation: BioMarin Pharmaceutical
name: Debra Lounsbury
role: STUDY_DIRECTOR
References:
citation: Schweighardt B, Tompkins T, Lau K, Jesaitis L, Qi Y, Musson DG, Farmer P, Haller C, Shaywitz AJ, Yang K, O'Neill CA. Immunogenicity of Elosulfase Alfa, an Enzyme Replacement Therapy in Patients With Morquio A Syndrome: Results From MOR-004, a Phase III Trial. Clin Ther. 2015 May 1;37(5):1012-1021.e6. doi: 10.1016/j.clinthera.2014.11.005. Epub 2014 Dec 6.