Clinical trial NCT01415427: Long-Term Efficacy and Safety Extension Study of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
Official title: A Multicenter, Multinational, Extension Study to Evaluate the Long-Term Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Mucopolysaccharidosis IV A
Morquio A Syndrome
MPS IVA
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: 2011-08-12
Enrollment: 173
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 extension study will evaluate the long-term efficacy and safety of BMN 110 2.0 mg/kg/week and/or BMN 110 2.0 mg/kg/every other week in patients with mucopolysaccharidosis IVA (Morquio A Syndrome).

Detailed description: This is a multi-center, multinational, extension study to evaluate 2 dose regimens of BMN 110 treatment in patients with MPS IVA who completed MOR-004.

The last study visit assessments for MOR-004 will constitute Baseline for this study. The first study drug dose of this protocol will occur on Week 0 of MOR-005, which is the same as the last visit (Week 24) of MOR-004. Initially, the study will be double-blind with patients previously randomized to BMN 110 in MOR-004 remaining on their assigned BMN 110 dose regimen (qw or qow dosing). The MOR-004 placebo patients will be re-randomized (1:1 ratio) to one of the 2 BMN 110 dose regimen groups: 2.0 mg/kg/qw or 2.0 mg/kg/qow.

There will be two study parts:

* Part 1 - randomized double-blind until the optimal BMN 110 dose regimen has been determined, based on the final primary efficacy analysis from MOR-004
* Part 2 - open-label BMN 110 treatment with the single optimal dose regimen

Eligibility criteria: Inclusion Criteria:

* Must have completed MOR-004
* Is willing and able to provide written, signed informed consent. Or in the case of patients under the age of 18 (or other age as defined by regional law or regulation), provide written assent (if required) and have written informed consent, signed by a legally authorize representative, after the nature of the study has been explained, and prior to performance of research-related procedures.
* If sexually active, must be willing to use an acceptable method of contraception while participating in the study.
* If female, of childbearing potential, must have a negative pregnancy test at Baseline and be willing to have additional pregnancy tests done during the study.

Exclusion Criteria:

* Is pregnant or breastfeeding, at Baseline, or planning to become pregnant (self or partner) at any time during the study.
* Has used any investigational product (other than BMN 110 in MOR-004), or investigational medical device, within 30 days prior to Baseline; or is required to use any investigational agent prior to completion of all scheduled study assessments.
* Was enrolled in a previous BMN 110 study, other than MOR-004.
* Has a 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 pose a safety risk, as determined by the Investigator.
* Has 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 6-minute Walk (6MW) Test - ITT
timeFrame: Baseline to week 168
measure: Change From Baseline in 6-minute Walk (6MW) Test - MPP
timeFrame: Baseline to week 168
Secondary outcomes:
measure: Change From Baseline in 3-minute Stair Climb Test - ITT
timeFrame: Baseline to week 168
measure: Change From Baseline in 3-minute Stair Climb Test - MPP
timeFrame: Baseline to week 168
measure: Change From Baseline in Urine Keratan Sulfate - ITT
timeFrame: Baseline to week 168
measure: Change From Baseline in Urine Keratan Sulfate - MPP
timeFrame: Baseline to week 168
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Oakland
country: United States
state: California
city: Orange
country: United States
state: California
city: Wilmington
country: United States
state: Delaware
city: Washington
country: United States
state: District of Columbia
city: Orlando
country: United States
state: Florida
city: Honolulu
country: United States
state: Hawaii
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: Rio de Janeiro
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: Marseille
country: France
city: Paris
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: Oslo
country: Norway
city: Coimbra
country: Portugal
city: Lisbon
country: Portugal
city: Doha
country: Qatar
city: Riyadh
country: Saudi Arabia
city: Santiago de Compostela
country: Spain
city: Taipei
country: Taiwan
city: Ankara
country: Turkey
city: Belfast
country: United Kingdom
city: Birmingham
country: United Kingdom
city: Birmingham
country: United Kingdom
city: London
country: United Kingdom
city: London
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: Hendriksz CJ, Parini R, AlSayed MD, Raiman J, Giugliani R, Mitchell JJ, Burton BK, Guelbert N, Stewart FJ, Hughes DA, Matousek R, Hawley SM, Decker C, Harmatz PR. Impact of long-term elosulfase alfa on activities of daily living in patients with Morquio A syndrome in an open-label, multi-center, phase 3 extension study. Mol Genet Metab. 2018 Feb;123(2):127-134. doi: 10.1016/j.ymgme.2017.11.015. Epub 2017 Dec 5.
citation: Hughes D, Giugliani R, Guffon N, Jones SA, Mengel KE, Parini R, Matousek R, Hawley SM, Quartel A. Clinical outcomes in a subpopulation of adults with Morquio A syndrome: results from a long-term extension study of elosulfase alfa. Orphanet J Rare Dis. 2017 May 23;12(1):98. doi: 10.1186/s13023-017-0634-0.
citation: Long B, Tompkins T, Decker C, Jesaitis L, Khan S, Slasor P, Harmatz P, O'Neill CA, Schweighardt B. Long-term Immunogenicity of Elosulfase Alfa in the Treatment of Morquio A Syndrome: Results From MOR-005, a Phase III Extension Study. Clin Ther. 2017 Jan;39(1):118-129.e3. doi: 10.1016/j.clinthera.2016.11.017. Epub 2016 Dec 10.