Long-Term Efficacy and Safety Extension Study of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)

Study Overview
=================
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

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)

Conditions
-----------------
Mucopolysaccharidosis IV A, Morquio A Syndrome, MPS IVA

Intervention / Treatment
-----------------
* Drug: BMN 110 - Weekly
* Drug: BMN 110 - Every Other Week


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 5 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BMN 110 Weekly<br>BMN 110 Weekly: In Part 1, patients will receive an intravenous infusion of BMN 110 at a dose of 2.0 mg/kg administered over a period of approximately 4 hours once a week. | Drug: BMN 110 - Weekly<br>* In Part 1, patients will receive intravenous (IV) infusions of study drug at a dose of 2.0 mg/kg/qw administered over a period of approximately 4 hours once a week. In Part 2, patients will continue to receive 2.0 mg/kg of BMN 110 every week, with no placebo.<br>* Other names: ERT;|
| Experimental: BMN 110 Every Other Week<br>BMN 110 Every Other Week: In Part 1, patients will receive an 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 will receive infusions of placebo on alternating weeks. | Drug: BMN 110 - Every Other Week<br>* In Part 1, patients will receive intravenous (IV) infusions of study drug at a dose of 2.0 mg/kg administered over a period of approximately 4 hours every other week. Patients randomized to the 2.0 mg/kg/qow arm will receive infusions of placebo on alternating weeks, to mask active drug weeks. In Part 2, patients will receive 2.0 mg/kg of BMN 110 every week, with no placebo.<br>* Other names: ERT;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 6-minute Walk (6MW) Test - ITT | Efficacy was assessed by changes from baseline in 6-minute walk test | Baseline to week 168 | 
| Change From Baseline in 6-minute Walk (6MW) Test - MPP | Efficacy was assessed by changes from baseline in 6-minute walk test | Baseline to week 168 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 3-minute Stair Climb Test - ITT | Efficacy was assessed by changes from baseline in 3-minute stair climb test. | Baseline to week 168 | 
| Change From Baseline in 3-minute Stair Climb Test - MPP | Efficacy was assessed by changes from baseline in 3-minute stair climb test. | Baseline to week 168 | 
| Change From Baseline in Urine Keratan Sulfate - ITT | Efficacy was assessed by changes from baseline in urine keratan sulfate (normalized to urine creatinine.) | Baseline to week 168 | 
| Change From Baseline in Urine Keratan Sulfate - MPP | Efficacy was assessed by changes from baseline in urine keratan sulfate (normalized to urine creatinine.) | Baseline to week 168 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
MPS IVA, Mucopolysaccharidosis IV type A, MPS IV Type A, Mucopolysaccharidosis 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