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

NCT00069641 | Completed Phase 2 Results DMC

• 1 other identifier: TKT024
• Study Type: interventional
• Target: 96
• Locations: 4 countries
• Sites: 9

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.

Conditions

Mucopolysaccharidosis II

Keywords

Mucopolysaccharidosis II; MPS II; Hunter Syndrome; iduronate-2-sulfatase; I2S; Iduronate-2-sulfatase deficiency

Outcome Measures

Primary Outcomes (1)

• Ranked Adjusted 2-Component Composite Variable Score Based on Change From Baseline to 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.

  Baseline, Week 53

Secondary Outcomes (6)

• Change From Baseline in Mean Global Joint Range of Motion (JROM) Score at Week 53

  Baseline, Week 53

• Mean Combined Liver and Spleen Volume at Baseline

  Baseline

• Percent Change From Baseline in Mean Combined Liver and Spleen Volume at Week 53

  Baseline, Week 53

• Change From Baseline in Mean Normalized Urine Glycosaminoglycan (GAG) Levels at Week 53

  Baseline, Week 53

• Mean Cardiac Left Ventricular Mass Index (LVMI) at Baseline

  Baseline

Study Arms (3)

Idursulfase weekly (0.5 mg/kg)

EXPERIMENTAL

Biological: Iduronate-2-sulfatase enzyme replacement therapy

Idursulfase every other week (0.5 mg/kg)

EXPERIMENTAL

Biological: iduronate-2-sulfatase enzyme replacement therapy

Placebo

PLACEBO COMPARATOR

Biological: Placebo

Interventions

iduronate-2-sulfatase enzyme replacement therapy BIOLOGICAL

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

Also known as: Elaprase

Idursulfase weekly (0.5 mg/kg)

Placebo BIOLOGICAL

Patients will receive weekly infusions of placebo.

Placebo

Eligibility Criteria

• Age: 5 Years - 25 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shire: lead

Study Sites (9)

Children's Hospital Oakland

Oakland, California, 94609, United States

Location

St. Louis Children's Hospital, Washington University

St Louis, Missouri, 63110, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Texas Children's Hospital, Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Hospital de Clinicas de Porto Alegre

Porto Alegre, Brazil

Location

Children's Hospital, Johannes-Gutenburg Universitaet Mainz

Mainz, Germany

Location

Addenbrooke's Hospital

Cambridge, England, CB2 2QQ, United Kingdom

Location

Great Ormond Street Hospital for Sick Children

London, England, WC1N3JH, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, England, M27 4HA, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 33874971 DERIVED

• 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.

  PMID: 23837440 DERIVED

MeSH Terms

Conditions

Mucopolysaccharidosis II; Sudden Infant Death

Interventions

idursulfase

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Death, Sudden; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infant Death

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2003
• First Posted: October 1, 2003
• Study Start: September 18, 2003
• Primary Completion: March 16, 2005
• Study Completion: March 16, 2005
• Last Updated: June 10, 2021
• Results First Posted: May 13, 2015

Record last verified: 2021-05

Locations

BR (1); DE (1); US (4); GB (3)