Iduronate-2-sulfatase Enzyme Replacement Therapy in Mucopolysaccharidosis II (MPS II)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00069641|
Recruitment Status : Completed
First Posted : October 1, 2003
Results First Posted : May 13, 2015
Last Update Posted : May 13, 2015
|Condition or disease||Intervention/treatment||Phase|
|Mucopolysaccharidosis II||Biological: Iduronate-2-sulfatase enzyme replacement therapy Biological: iduronate-2-sulfatase enzyme replacement therapy Biological: Placebo||Phase 2 Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||96 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|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 in Patients With MPS II|
|Study Start Date :||September 2003|
|Actual Primary Completion Date :||March 2005|
|Actual Study Completion Date :||March 2005|
|Experimental: Idursulfase weekly (0.5 mg/kg)||
Biological: Iduronate-2-sulfatase enzyme replacement therapy
Patients will receive weekly infusions of idursulfase at a dose of 0.5 mg/kg.
Other Name: Elaprase
|Experimental: Idursulfase every other week (0.5 mg/kg)||
Biological: iduronate-2-sulfatase enzyme replacement therapy
Patients will receive every other week infusions of idursulfase at a dose of 0.5 mg/kg.
Other Name: Elaprase
|Placebo Comparator: Placebo||
Patients will receive weekly infusions of placebo.
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00069641
|United States, California|
|Children's Hospital Oakland|
|Oakland, California, United States, 94609|
|United States, Missouri|
|St. Louis Children's Hospital, Washington University|
|St. Louis, Missouri, United States, 63110|
|United States, North Carolina|
|University of North Carolina at Chapel Hill|
|Chapel Hill, North Carolina, United States, 27599|
|United States, Texas|
|Texas Children's Hospital, Baylor College of Medicine|
|Houston, Texas, United States, 77030|
|Hospital de Clinicas de Porto Alegre|
|Porto Alegre, Brazil|
|Children's Hospital, Johannes-Gutenburg Universitaet Mainz|
|Cambridge, England, United Kingdom, CB2 2QQ|
|Great Ormond Street Hospital for Sick Children|
|London, England, United Kingdom, WC1N3JH|
|Royal Manchester Children's Hospital|
|Manchester, England, United Kingdom, M27 4HA|
|Principal Investigator:||Joseph Muenzer, MD, PhD||University of North Carolina, Chapel Hill|
|Principal Investigator:||Rick A. Martin, MD||St. Louis Children's Hospital, Washington University|
|Principal Investigator:||Paul Harmatz, MD||Children's Hospital & Research Center Oakland|
|Principal Investigator:||Christine Eng, MD||Texas Children's Hospital, Baylor College of Medicine|
|Principal Investigator:||Michael Beck, MD, PhD||Children's Hospital, Johannes-Gutenburg Universitaet Mainz|
|Principal Investigator:||Roberto Giugliani, MD, PhD||Hospital de Clinicas de Porto Alegre|
|Principal Investigator:||Ashok Vellodi, MD||Great Ormond Street Hospital for Sick Children|
|Principal Investigator:||Edmund Wraith, MD||Royal Manchester Children's Hospital|
|Principal Investigator:||Uma Ramaswami, MD||Cambridge University Hospitals NHS Foundation Trust|