- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00069641
Iduronate-2-sulfatase Enzyme Replacement Therapy in Mucopolysaccharidosis II (MPS II)
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 Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
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Porto Alegre, Brazil
- Hospital de Clinicas de Porto Alegre
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Mainz, Germany
- Children's Hospital, Johannes-Gutenburg Universitaet Mainz
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England
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Cambridge, England, United Kingdom, CB2 2QQ
- Addenbrooke's Hospital
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London, England, United Kingdom, WC1N3JH
- Great Ormond Street Hospital for Sick Children
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Manchester, England, United Kingdom, M27 4HA
- Royal Manchester Children's Hospital
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California
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Oakland, California, United States, 94609
- Children's Hospital Oakland
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Missouri
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Saint Louis, Missouri, United States, 63110
- St. Louis Children's Hospital, Washington University
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North Carolina
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Chapel Hill, North Carolina, United States, 27599
- University of North Carolina At Chapel Hill
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Texas
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Houston, Texas, United States, 77030
- Texas Children's Hospital, Baylor College of Medicine
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
To be eligible to participate in this study, patients must meet the following inclusion criteria prior to enrollment:
- The diagnosis of MPS II will be determined by the investigator based upon both clinical and biochemical criteria.
All patients must have at least one of the following Clinical Criteria considered by the investigator to be MPS II-related:
- Hepatosplenomegaly
- Radiographic evidence of dysostosis multiplex
- Valvular heart disease
- Evidence of obstructive pulmonary disease
In addition, patients must have the following Biochemical Criteria:
- Documented deficiency in iduronate-2-sulfastase enzyme activity of less than or equal to 10% of the lower limit of the normal range as measured in plasma, fibroblasts, or leukocytes (based on normal range of measuring laboratory).
- A normal enzyme activity level of one other sulfatase as measured in plasma, fibroblasts, or leukocytes (based on normal range of measuring laboratory).
- Must be male, 5 to 25 years of age.
- Forced vital capacity of <80% of predicted obtained at the baseline evaluation of this study.
- Must be able to adequately perform the testing required in this study, including reproducible pulmonary function testing by spirometry, as judged by the investigator.
- Patient, patient's parent(s), or legally authorized guardian must have voluntarily signed an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent form after all relevant aspects of the study have been explained and discussed with the patient.
Exclusion Criteria:
Patients meeting any of the following criteria are not eligible for participation in this study:
- Patient has received treatment with another investigational therapy within the past 60 days.
- Patient, patient's parent(s), or patient's legal guardian is unable to understand the nature, scope, and possible consequences of the study.
- Patient is unable to comply with the protocol (e.g., due to a medical condition such as cervical cord compression or uncooperative attitude) or is unlikely to complete the study, as determined by the investigator.
- Patient has a tracheostomy.
- Patient has received a bone marrow or cord blood transplant.
- Patient with known hypersensitivity to any of the components of iduronate-2-sulfatase.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Placebo Comparator: Placebo
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Patients will receive weekly infusions of placebo.
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Experimental: Idursulfase weekly (0.5 mg/kg)
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Patients will receive weekly infusions of idursulfase at a dose of 0.5 mg/kg.
Other Names:
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Experimental: Idursulfase every other week (0.5 mg/kg)
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Patients will receive every other week infusions of idursulfase at a dose of 0.5 mg/kg.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Ranked Adjusted 2-Component Composite Variable Score Based on Change From Baseline to Week 53
Time Frame: Baseline, Week 53
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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.
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Baseline, Week 53
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change From Baseline in Mean Global Joint Range of Motion (JROM) Score at Week 53
Time Frame: Baseline, Week 53
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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).
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Baseline, Week 53
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Mean Combined Liver and Spleen Volume at Baseline
Time Frame: Baseline
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Liver and Spleen volume was determined by Magnetic Resonance Imaging (MRI).
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Baseline
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Percent Change From Baseline in Mean Combined Liver and Spleen Volume at Week 53
Time Frame: Baseline, Week 53
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Liver and Spleen volume was determined by Magnetic Resonance Imaging (MRI).
Change was calculated at Week 53 from baseline.
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Baseline, Week 53
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Change From Baseline in Mean Normalized Urine Glycosaminoglycan (GAG) Levels at Week 53
Time Frame: Baseline, Week 53
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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).
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Baseline, Week 53
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Mean Cardiac Left Ventricular Mass Index (LVMI) at Baseline
Time Frame: Baseline
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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.
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Baseline
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Percent Change From Baseline in Mean Cardiac Left Ventricular Mass Index (LVMI) at Week 53
Time Frame: Baseline, Week 53
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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.
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Baseline, Week 53
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Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Tandon PK, Kakkis ED. The multi-domain responder index: a novel analysis tool to capture a broader assessment of clinical benefit in heterogeneous complex rare diseases. Orphanet J Rare Dis. 2021 Apr 19;16(1):183. doi: 10.1186/s13023-021-01805-5. Review.
- Raluy-Callado M, Chen WH, Whiteman DA, Fang J, Wiklund I. The impact of Hunter syndrome (mucopolysaccharidosis type II) on health-related quality of life. Orphanet J Rare Dis. 2013 Jul 10;8:101. doi: 10.1186/1750-1172-8-101.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Metabolic Diseases
- Nervous System Diseases
- Neurologic Manifestations
- Neurobehavioral Manifestations
- Genetic Diseases, Inborn
- Genetic Diseases, X-Linked
- Connective Tissue Diseases
- Carbohydrate Metabolism, Inborn Errors
- Metabolism, Inborn Errors
- Lysosomal Storage Diseases
- Mucinoses
- Mental Retardation, X-Linked
- Intellectual Disability
- Heredodegenerative Disorders, Nervous System
- Mucopolysaccharidosis II
- Mucopolysaccharidoses
Other Study ID Numbers
- TKT024
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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