The primary objective of this study was to evaluate the safety of a 2.0 mg/kg/week and a 4.0 mg/kg/week of BMN 110 in patients with Morquio A syndrome for up to 196 weeks. Secondary objectives were to investigate the effect of the two doses on exercise capacity for up to 196 weeks. In addition, the pharmacokinetic (PK) parameters of both doses of BMN 110 was assessed.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
25
Weekly IV infusions of BMN 110 at 2.0 mg/kg/week over a period of approximately 4 hours per infusion for up to 192 weeks.
Weekly IV infusions of BMN 110 at 4.0 mg/kg/week over a period of approximately 4 hours per infusion for 27 weeks, and will eventually transition to 2.0 mg/kg/week for up to an additional 166 weeks.
Unnamed facility
Oakland, California, United States
Unnamed facility
Chicago, Illinois, United States
Unnamed facility
New York, New York, United States
Unnamed facility
Houston, Texas, United States
Safety Evaluation
The primary objective of the study is to evaluate the safety of weekly infusions of BMN 110; the safety variables included Adverse Events (AEs). The primary outcome measure data is presented in more detail under the Adverse Events section.
Time frame: Entire Study Period, up to 192 weeks or ETV (early termination visit)
6-minute Walk Test (6MWT)
Change from baseline to Week 12, 24, and 52 as measured in distance walked (meters) in 6MWT.
Time frame: Baseline, Week 12, 24, and 52
3-minute Stair Climb Test (3MSCT)
Change from baseline to Week 12, 24, and 52 as measured in speed (stairs/min) in 3MSCT.
Time frame: Baseline, Week 12, 24, and 52
Respiratory Function Test (MVV and FVC)
Respiratory Function was assessed by spirometry in accordance with American Thoracic Society standards. Percent change from baseline to Week 12, 24, and 52 as measured by Maximum Voluntary Ventilation (MVV, L/min) Percent change from baseline to Week 12, 24, and 52 as measured by Forced Vital Capacity (FVC, L)
Time frame: Baseline, Week 12, 24, and 52
Normalized Urine Keratan Sulfate (uKS)
Urinary KS was measured by a quantitative method and normalized using the sample urinary creatinine measurement. Percent change from baseline to Week 12, 24, and 52 in normalized urine keratan sulfate (ug/mg).
Time frame: Baseline, Week 12, 24, and 52
Cardiopulmonary Exercise Testing (CPET) - Duration of Exercise
Subjects performed maximal incremental exercise testing using an electronically braked upright cycle ergometer. Cycle ergometry is a method of CPET that may be feasible in subjects who have orthopedic, peripheral vascular, or neurological limitations that restrict weight bearing. Change from baseline to Week 25 and 52 as measured by the CPET Duration of Exercise (min)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Unnamed facility
Calgary, Alberta, Canada
Unnamed facility
Toronto, Ontario, Canada
Unnamed facility
Montreal, Quebec, Canada
Unnamed facility
Sherbrook, Quebec, Canada
Unnamed facility
Hamburg, Germany
Unnamed facility
Belfast, Northern Ireland, United Kingdom
...and 1 more locations
Time frame: Baseline, Week 25 and 52
Cardiopulmonary Exercise Testing (CPET) - Peak Workload
Subjects performed maximal incremental exercise testing using an electronically braked upright cycle ergometer. Cycle ergometry is a method of CPET that may be feasible in subjects who have orthopedic, peripheral vascular, or neurological limitations that restrict weight bearing. Percent change from baseline to Week 25 and 52 as measured by the CPET Peak workload (watt)
Time frame: Baseline, Week 25 and 52
Cardiopulmonary Exercise Testing (CPET) - O2 Pulse
Subjects performed maximal incremental exercise testing using an electronically braked upright cycle ergometer. Cycle ergometry is a method of CPET that may be feasible in subjects who have orthopedic, peripheral vascular, or neurological limitations that restrict weight bearing. Percent change from baseline to Week 25 and 52 as measured by the CPET O2 pulse (ml/beat)
Time frame: Baseline, Week 25 and 52
Cardiopulmonary Exercise Testing (CPET) - Aerobic Efficiency
Subjects performed maximal incremental exercise testing using an electronically braked upright cycle ergometer. Cycle ergometry is a method of CPET that may be feasible in subjects who have orthopedic, peripheral vascular, or neurological limitations that restrict weight bearing. Percent change from baseline to Week 25 and 52 as measured by the CPET Aerobic Efficiency (ml/watt). Note that decline in Aerobic Efficiency translate into an improvement
Time frame: Baseline, Week 25 and 52
Muscle Strength Testing (MST) - Knee Extension Test
Change from baseline to Week 25 and 52 as measured by the peak force in MST knee extension test (newton meters).
Time frame: Baseline, Week 25 and 52
Muscle Strength Testing (MST) - Knee Flexion Test
Percent change from baseline to Week 25 and 52 as measured by the peak force in MST knee flexion test (newton meters).
Time frame: Baseline, Week 25 and 52
Muscle Strength Testing (MST) - Elbow Flexion Test
Percent change from baseline to Week 25 and 52 as measured by the peak force in MST elbow flexion test (newton meters).
Time frame: Baseline, Week 25 and 52
Adolescent Pediatric Pain Tool (APPT) - Pain Intensity
The APPT is a validated, multidimensional tool to evaluate pain in children, adolescents, and young adults. The complete APPT is measured in three parts - Part 1 of the APPT scale determines the subject's pain locations using a body template. Part 2 of the APPT scale determines the intensity of the pain using a 10 cm visual analog scale (VAS) with the lowest point of the scale (0) labeled No Pain and the highest point on the scale (10) labeled Worst Possible Pain. Intermediate regions of the sale were labeled with 3 intermediate descriptors (Little Pain, Medium Pain, and Large Pain). Part 3 of the APPT scale characterizes the pain by tracking the number and percentage of words selected by subjects to describe their pain from a total of 57 choices. Part 2 corresponds most closely to other typically used pain scales (based on VAS) and for this reason the results from Part 2 are presented here. Change from baseline to Week 12, 24, and 52 in pain intensity.
Time frame: Baseline, Week 12, 24, and 52