Iduronate-2-Sulfatase Enzyme Replacement Therapy in Mucopolysaccharidosis II (MPS II)

This study has been completed.
Information provided by:
Shire Human Genetic Therapies, Inc. Identifier:
First received: September 29, 2003
Last updated: November 15, 2007
Last verified: November 2007

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.

Condition Intervention Phase
Mucopolysaccharidosis II
Drug: Iduronate-2-sulfatase enzyme replacement therapy
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by Shire Human Genetic Therapies, Inc.:

Study Start Date: September 2003
Detailed Description:

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.


Ages Eligible for Study:   5 Years to 25 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

To be eligible to participate in this study, patients must meet the following inclusion criteria prior to enrollment:

  1. The diagnosis of MPS II will be determined by the investigator based upon both clinical and biochemical criteria.
  2. 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
  3. 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).
  4. Must be male, 5 to 25 years of age.
  5. Forced vital capacity of <80% of predicted obtained at the baseline evaluation of this study.
  6. Must be able to adequately perform the testing required in this study, including reproducible pulmonary function testing by spirometry, as judged by the investigator.
  7. 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:

  1. Patient has received treatment with another investigational therapy within the past 60 days.
  2. Patient, patient's parent(s), or patient's legal guardian is unable to understand the nature, scope, and possible consequences of the study.
  3. 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.
  4. Patient has a tracheostomy.
  5. Patient has received a bone marrow or cord blood transplant.
  6. Patient with known hypersensitivity to any of the components of iduronate-2-sulfatase.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: 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
Mainz, Germany
United Kingdom
Addenbrooke's Hospital
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
Sponsors and Collaborators
Shire Human Genetic Therapies, Inc.
  More Information

No publications provided by Shire Human Genetic Therapies, Inc.

Additional publications automatically indexed to this study by Identifier (NCT Number): Identifier: NCT00069641     History of Changes
Other Study ID Numbers: TKT024
Study First Received: September 29, 2003
Last Updated: November 15, 2007
Health Authority: United States: Food and Drug Administration

Keywords provided by Shire Human Genetic Therapies, Inc.:
Mucopolysaccharidosis II
Hunter Syndrome
Iduronate-2-sulfatase deficiency

Additional relevant MeSH terms:
Mucopolysaccharidosis II
Carbohydrate Metabolism, Inborn Errors
Connective Tissue Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Heredodegenerative Disorders, Nervous System
Intellectual Disability
Lysosomal Storage Diseases
Mental Retardation, X-Linked
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
Neurobehavioral Manifestations
Neurologic Manifestations processed this record on May 04, 2015