Clinical Trial: Efficacy and Safety Study of BMN 110 for Morquio A Syndrome Patients Who Have Limited Ambulation

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Phase 2, Open-label, Multinational Study to Evaluate the Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome) Who Have Limited Ambulation

Brief Summary: The primary objective of this study is to evaluate the effect of 2.0 mg/kg/week BMN 110 in a patient population that has limited ambulation, in a period of up to 144 weeks.

Detailed Summary:

Effect is defined by the following key domains:

  • Upper extremity function and dexterity
  • Mobility

Sponsor: BioMarin Pharmaceutical

Current Primary Outcome:

  • Percent Change From Baseline in Speed as Measured in Functional Dexterity Test (FDT) [ Time Frame: Up to 96 weeks ]
    FDT assesses the ability to use the hand in daily tasks. The test involves turning 16 wooden pegs over as quickly as possible on a hardwood pegboard with one hand requiring a three-jaw chuck prehension pattern between the fingers and thumb within a two-minute time limit. Hand function is evaluated by how fast a patient can turn over pegs in the given time limit, i.e. speed (number of pegs/minute).
  • Change From Baseline in Strength as Assessed by Grip and Pinch Test (GPT) [ Time Frame: Up to 96 weeks ]
    A grip-strength dynamometer and a pinch meter were used to measure grip strength and pinch strength. The results report change from baseline in strength for dominant and non-dominant hand in a forearm and wrist supported position.
  • Percent Change From Baseline in Speed as Measured in Timed 25-Foot Walk Test (25FWT) [ Time Frame: Up to 96 weeks ]
    The timed 25-Foot Walk Test (25FWT) is an assessment of mobility and performance of leg function. The patient was instructed to walk a marked 25-foot course as quickly as possible in a time limit of 3 minutes and immediately walk back the same distance when reaching one end.The patient is allowed to use any ambulation method to move. The outcome measures the speed (feet / min) of moving.


Original Primary Outcome: Efficacy will be determined/summarized by percent changes of the domain scores for upper extremity function, dexterity, mobility, pain, and self-care and functional ability testing from baseline. [ Time Frame: Up to 48 weeks ]

  • Upper extremity function will be tested using the Grip-Pinch Test.
  • Dexterity will be tested using the Functional Dexterity Test.
  • Mobility will be tested using the 25 Foot Walk test
  • Pain will be determined by the Brief Pain Inventory-Short Form questionnaire or the Adolescent Pediatric Pain Tool
  • Functional/self care abilities will be determined using Pediatric Outcomes Data Collection Instrument (PODCI) or the SF-36 questionnaire.

Efficacy will be measured at the following timepoints: Baseline, Week 12, Week 24, Week 36,and Week 48/ ETV



Current Secondary Outcome: Percent Change From Baseline in Normalized Urine Keratan Sulfate (uKS) [ Time Frame: Up to 96 weeks ]

Urinary keratan sulfate and urinary creatinine were measured through quantitative analysis. uKS is normalized to creatinine.


Original Secondary Outcome:

  • Change in respiratory function using a summarized analysis of the percentage change in FET, FIVC, FVC, FEV1, MVV and optional TLC values from the Baseline visit. [ Time Frame: Up to 48 weeks ]
    Timepoints: Baseline, Week 24, and Week 48
  • Change in plasma and urinary KS over time as determined by descriptive statistics. [ Time Frame: Up to 48 weeks ]
    Timepoints: Baseline, Week 2, Week 4, Week 6, Week 12, Week 24, Week 36, Week 48/ ETV
  • Assessment of effect on sleep apnea results as calculated using the Apnea-hypopnea index(AHI). [ Time Frame: Up to 48 weeks ]
    A subset of approximately 5 patients at selected sites who have abnormal overnight pulse oximetry readings and who provide additional informed consent will be assessed for sleep apnea.


Information By: BioMarin Pharmaceutical

Dates:
Date Received: September 17, 2012
Date Started: August 2012
Date Completion:
Last Updated: December 8, 2015
Last Verified: December 2015