Clinical trial NCT01609062: Safety and Exercise Study of Two Doses of BMN 110 for Morquio A Syndrome
Official title: A Randomized, Double-Blind, Pilot Study of the Safety and Physiological Effects of Two Doses of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Mucopolysaccharidosis IVA
Morquio A Syndrome
MPS IVA
Keywords: Mucopolysaccharidosis IVA Type A
MPS IVA 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
MOR-008
CPET
MST
muscle strength test
physiological effect
Lead sponsor: BioMarin Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2012-05-31
Enrollment: 25
Sex: ALL
Minimum age (years): 7
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Is willing and able to provide written, signed informed consent (or patient's legally authorized representative) after the nature of the study has been explained and prior to performance of any research- related procedure. Also, patients who do not meet country and local age requirements for informed consent must be willing and able to 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 performance of any research-related procedure.
* Has documented clinical diagnosis of Morquio A Syndrome (MPS IVA) based on clinical signs and symptoms of MPS IVA and documented reduced fibroblast or leukocyte N-acetylgalactosamine-6-sulfatase (GALNS) enzyme activity or genetic testing confirming diagnosis of MPS IVA.
* Is at least 7 years of age
* Is able to walk ≥ 200 meters as assessed by the 6-minute Walk Test (6MWT)
* If sexually active, is 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 the Screening Visit and be willing to have additional pregnancy tests during the study
* Is willing and able to perform all study procedures, including cardiopulmonary exercise testing (CPET)

Exclusion Criteria:

* Inability to perform an exercise test due to limited mobility
* Body weight greater than 95 kg at Screening
* Severe, untreated sleep apnea as measured during Screening with a home sleep testing device
* Patients with a history of, or current condition of sleep apnea or sleep disordered breathing under adequate treatment may be enrolled if approved by the medical monitor.
* Requirement for supplemental oxygen
* Use of ventilator assistance in the 3 months prior to study entry
* Use of positive airway pressure (continuous positive airway pressure, CPAP, or bilevel airway pressure) for treatment of sleep apnea or sleep disordered breathing is allowed if settings have been stable for at least 1 month prior to study entry, and is approved by the medical monitor.
* 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 previous hematopoietic stem cell transplant (HSCT)
* Has received previous treatment with BMN 110
* Has a known hypersensitivity to BMN 110 or its excipients
* Has had major surgery within 3 months prior to study entry or is planning to have a major surgery during the duration of the study
* Use of any other investigational product (IP) or investigational medical device within 30 days prior to the beginning of the Screening Period or requires any investigational agent prior to completion of all scheduled study assessments
* Is pregnant or breastfeeding during the Screening Period or planning to become pregnant (self or partner) at any time during the study
* Has a concurrent disease or condition that may interfere with study participation or safety, and/or ability to perform study procedures as determined by the Investigator
* Has any condition that, in the view of the Investigator, poses a safety risk to the patient
* 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: Safety Evaluation
timeFrame: Entire Study Period, up to 192 weeks or ETV (early termination visit)
Secondary outcomes:
measure: 6-minute Walk Test (6MWT)
timeFrame: Baseline, Week 12, 24, and 52
measure: 3-minute Stair Climb Test (3MSCT)
timeFrame: Baseline, Week 12, 24, and 52
measure: Respiratory Function Test (MVV and FVC)
timeFrame: Baseline, Week 12, 24, and 52
measure: Normalized Urine Keratan Sulfate (uKS)
timeFrame: Baseline, Week 12, 24, and 52
measure: Cardiopulmonary Exercise Testing (CPET) - Duration of Exercise
timeFrame: Baseline, Week 25 and 52
measure: Cardiopulmonary Exercise Testing (CPET) - Peak Workload
timeFrame: Baseline, Week 25 and 52
measure: Cardiopulmonary Exercise Testing (CPET) - O2 Pulse
timeFrame: Baseline, Week 25 and 52
measure: Cardiopulmonary Exercise Testing (CPET) - Aerobic Efficiency
timeFrame: Baseline, Week 25 and 52
measure: Muscle Strength Testing (MST) - Knee Extension Test
timeFrame: Baseline, Week 25 and 52
measure: Muscle Strength Testing (MST) - Knee Flexion Test
timeFrame: Baseline, Week 25 and 52
measure: Muscle Strength Testing (MST) - Elbow Flexion Test
timeFrame: Baseline, Week 25 and 52
measure: Adolescent Pediatric Pain Tool (APPT) - Pain Intensity
timeFrame: Baseline, Week 12, 24, and 52
Other outcomes:
Locations:
city: Oakland
country: United States
state: California
city: Chicago
country: United States
state: Illinois
city: New York
country: United States
state: New York
city: Houston
country: United States
state: Texas
city: Calgary
country: Canada
state: Alberta
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Sherbrook
country: Canada
state: Quebec
city: Hamburg
country: Germany
city: Belfast
country: United Kingdom
state: Northern Ireland
city: Manchester
country: United Kingdom
Study officials:
affiliation: BioMarin Pharmaceutical
name: Adam Shaywitz, MD PhD
role: STUDY_DIRECTOR
References:
citation: Berger KI, Burton BK, Lewis GD, Tarnopolsky M, Harmatz PR, Mitchell JJ, Muschol N, Jones SA, Sutton VR, Pastores GM, Lau H, Sparkes R, Shaywitz AJ. Cardiopulmonary Exercise Testing Reflects Improved Exercise Capacity in Response to Treatment in Morquio A Patients: Results of a 52-Week Pilot Study of Two Different Doses of Elosulfase Alfa. JIMD Rep. 2018;42:9-17. doi: 10.1007/8904_2017_70. Epub 2017 Nov 21.