Clinical Trial: Iduronate-2-sulfatase Enzyme Replacement Therapy in Mucopolysaccharidosis II (MPS II)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase II/III, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Weekly and Every Other Week Dosing Regimens of Iduronate-2-Sulfatase Enzyme Replacement Therapy

Brief Summary: The purpose of this study is to determine whether the administration of iduronate-2-sulfatase enzyme in a weekly or every other week therapy frequency is safe and efficacious in patients with MPS II.

Detailed Summary: MPS II is a rare, X-linked, lysosomal storage disorder caused by a deficiency in the enzyme iduronate-2-sulfatase. Because of this deficiency, glycosaminoglycans (GAG) accumulate in multiple tissues and organs, resulting in progressive cellular and organ system dysfunction. The purpose of this study is to determine if one year of therapy with iduronate-2-sulfatase enzyme replacement therapy, at a dose of 0.5mg/kg, weekly or every other week, is safe, and results in clinically meaningful improvement in multiple organ function, compared with a placebo group. Upon completion of the study, patients will be eligible to enroll in an open-label maintenance study.
Sponsor: Shire

Current Primary Outcome: Ranked Adjusted 2-Component Composite Variable Score Based on Change From Baseline to Week 53 [ Time Frame: Baseline, Week 53 ]

The 2-component composite variable consists of the sum of the ranked changes from baseline to Week 53 for percent predicted Forced Vital Capacity (FVC) and 6-Minute Walking Test (6MWT) total distance walked. For the 2 treatment groups being compared, ranking occurred within the comparison treatment groups combined (idursulfase weekly and placebo treatment groups). These comparison groups were pooled and ranked for each component separately. Within each component (% predicted FVC, 6MWT), the change from baseline was then ranked. The lowest change value was assigned a rank of 1, the next lowest a rank of 2, etc. The composite score for each participant was the sum of the 2 ranked scores corresponding to the 2 individual components (% predicted FVC and 6MWT) for each participant. Thus, the greater the composite score (greater the sum of the ranks of the changes from baseline, where the lowest change was ranked as 1), the greater the improvement.


Original Primary Outcome:

Current Secondary Outcome:

  • Change From Baseline in Mean Global Joint Range of Motion (JROM) Score at Week 53 [ Time Frame: Baseline, Week 53 ]
    Change was calculated at Week 53 from baseline. Global JROM (% of normal range of motion) is the average of 11 ratios multiplied by 100. Ratios are Left/Right means of passive range of motion in Shoulder (Flexion/Extension, Abduction, Internal/External Rotation), Elbow (Flexion/Extension), Wrist (Flexion/Extension), Index Finger (Flexion/Extension [Combined Metacarpophalangeal joint (MCP), Proximal interphalangeal joint (PIP), Distal interphalangeal joint (DIP) motion]), Hip (Flexion/Extension, Abduction, Internal/External Rotation), Knee (Flexion/Extension), and Ankle (Dorsiflexion) divided by the normal range (American Academy of Orthopedic Surgeons and American Medical Association).
  • Mean Combined Liver and Spleen Volume at Baseline [ Time Frame: Baseline ]
    Liver and Spleen volume was determined by Magnetic Resonance Imaging (MRI).
  • Percent Change From Baseline in Mean Combined Liver and Spleen Volume at Week 53 [ Time Frame: Baseline, Week 53 ]
    Liver and Spleen volume was determined by Magnetic Resonance Imaging (MRI). Change was calculated at Week 53 from baseline.
  • Change From Baseline in Mean Normalized Urine Glycosaminoglycan (GAG) Levels at Week 53 [ Time Frame: Baseline, Week 53 ]
    Mean normalized urine GAG was analyzed using urine testing. Change was calculated at Week 53 from baseline. The urine GAG levels were normalized to urine creatinine and were reported as microgram GAG per milligram creatinine (mcg GAG/mg creatinine).
  • Mean Cardiac Left Ventricular Mass Index (LVMI) at Baseline [ Time Frame: Baseline ]
    Cardiac LVMI was determined by echocardiography. LVMI is the left ventricular mass (LVM, in grams [g]) indexed to body surface area (BSA), in square meter [m^2]. LVMI (in gram per square meter [g/m^2]) = LVM divided by BSA.
  • Percent Change From Baseline in Mean Cardiac Left Ventricular Mass Index (LVMI) at Week 53 [ Time Frame: Baseline, Week 53 ]
    Cardiac LVMI was determined by echocardiography. Change was calculated at Week 53 from baseline. LVMI is the LVM, in grams indexed to BSA, in square meter [m^2]. LVMI in g/m^2 = LVM divided by BSA.


Original Secondary Outcome:

Information By: Shire

Dates:
Date Received: September 29, 2003
Date Started: September 2003
Date Completion:
Last Updated: April 27, 2015
Last Verified: January 2014