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

NCT ID: NCT00069641

Last Updated: 2021-06-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-09-18
• Study Completion Date: 2005-03-16

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 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.

Conditions

Mucopolysaccharidosis II

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Idursulfase weekly (0.5 mg/kg)

Group Type: EXPERIMENTAL

Iduronate-2-sulfatase enzyme replacement therapy

Intervention Type: BIOLOGICAL

Patients will receive weekly infusions of idursulfase at a dose of 0.5 mg/kg.

Idursulfase every other week (0.5 mg/kg)

Group Type: EXPERIMENTAL

iduronate-2-sulfatase enzyme replacement therapy

Intervention Type: BIOLOGICAL

Patients will receive every other week infusions of idursulfase at a dose of 0.5 mg/kg.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Patients will receive weekly infusions of placebo.

Interventions

Iduronate-2-sulfatase enzyme replacement therapy

Patients will receive weekly infusions of idursulfase at a dose of 0.5 mg/kg.

Intervention Type: BIOLOGICAL

iduronate-2-sulfatase enzyme replacement therapy

Patients will receive every other week infusions of idursulfase at a dose of 0.5 mg/kg.

Intervention Type: BIOLOGICAL

Placebo

Patients will receive weekly infusions of placebo.

Intervention Type: BIOLOGICAL

Other Intervention Names

Elaprase; Elaprase

Eligibility Criteria

Inclusion Criteria

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.

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 25 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Children's Hospital Oakland

Oakland, California, United States

St. Louis Children's Hospital, Washington University

St Louis, Missouri, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Texas Children's Hospital, Baylor College of Medicine

Houston, Texas, United States

Hospital de Clinicas de Porto Alegre

Porto Alegre, , Brazil

Children's Hospital, Johannes-Gutenburg Universitaet Mainz

Mainz, , Germany

Addenbrooke's Hospital

Cambridge, England, United Kingdom

Great Ormond Street Hospital for Sick Children

London, England, United Kingdom

Royal Manchester Children's Hospital

Manchester, England, United Kingdom

Countries

United States; Brazil; Germany; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 33874971 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23837440 (View on PubMed)

Other Identifiers

TKT024

Identifier Type: -

Identifier Source: org_study_id