An Observational Study Evaluating Anti-Idursulfase Serum Antibody Response in Hunter Syndrome Patients

A Multi-Center Observational Study Evaluating Anti-Idursulfase Serum Antibody Response in Hunter Syndrome Patients Enrolled in the Hunter Outcome Survey (HOS) Receiving Idursulfase Enzyme Replacement Therapy

The objective of this study is to evaluate the effect of anti-idursulfase antibodies on idursulfase safety (measured by infusion related adverse events) between patients who develop anti-idursulfase antibodies and patients who do not after long-term idursulfase enzyme replacement therapy (ERT).

Study Overview

• Status: Completed
• Conditions: Hunter Syndrome
• Intervention / Treatment: Biological: Idursulfase

Detailed Description

This study is being conducted to satisfy post-marketing commitments to monitor anti-idursulfase antibody development in Hunter syndrome patients after long-term idursulfase enzyme replacement therapy. The study will be conducted as a sub-study within the Hunter Outcome Survey (HOS). Hunter syndrome patients in the HOS who have previously received idursulfase as well as treatment-naive patients who will begin idursulfase treatment within 30 days of study enrollment will be included.

• Study Type: Observational
• Enrollment (Actual): 26

Contacts and Locations

Study Locations

• Brazil
  • RS
    • Porto Alegre, RS, Brazil, 90035-903
      • Hospital de Clinicas de Porto Alegre, Servico de Genetica Medica
• United Kingdom
  • Birmingham, United Kingdom, B46NH
    • Birmingham Children's Hospital
  • London, United Kingdom, WC1N 3JH
    • Great Ormond Street Hospital
  • Manchester, United Kingdom, M139WL
    • Central Manchester University Hospitals, St. Mary's Hospital
• United States
  • California
    • Oakland, California, United States, 94609
      • Children's Hospital & Research Center Oakland
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Children's Hospitals and Clinics of Minnesota, Division of Genetics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

Patients with Hunter syndrome

Description

Inclusion Criteria:

Patients must meet all of the following criteria to be considered eligible for enrollment:

• The patient is male and enrolled in the HOS (i.e., meets the entry criteria of a documented diagnosis of Hunter syndrome)
• The patient is ≥ 5 years-old
• The patient is on idursulfase treatment or scheduled to begin idursulfase treatment within 30 days of study enrollment
• The patient, patient's parent(s), or patient's 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, patient's parent(s), or patient's legally authorized guardian.

Exclusion Criteria:

Patients who meet any of the following criteria are not eligible for this study:

• The patient has received biologic/ERT products other than idursulfase, or other investigational product(s) for any reason within 30 days prior to study entry.
• The patient has a life expectancy of < 2 years
• The patient is unable to comply with the protocol, e.g., has a clinically relevant medical condition making implementation of the protocol difficult; has an uncooperative attitude; is unable to return for safety evaluations; or is otherwise unlikely to complete the study, as determined by the Investigator.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Elaprase; Idursulfase 0.5 mg/kg Weekly	Biological: Idursulfase; Patients received idursulfase as prescribed by their physician following locally approved prescribing information. Patients will not be provided idursulfase by Shire Human Genetic Therapies, Inc. or the HOS.; Other Names: Elaprase

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infusion-Related Adverse Event (IRAE) Rates Between IgG Anti-idursulfase Antibody Positive (Ab+) and Anti-idursulfase IgG Antibody Negative (Ab-) Patients	The primary analysis of how presence of antibodies affected IRAE rates was performed based on a negative binomial regression model. This was done to account for potentially differential follow-up time between antibody groups.	Baseline to 109 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in uGAG Levels to 109 Weeks	Urine GAG	Baseline to 109 Weeks

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• Giugliani R, Harmatz P, Jones SA, Mendelsohn NJ, Vellodi A, Qiu Y, Hendriksz CJ, Vijayaraghavan S, Whiteman DA, Pano A. Evaluation of impact of anti-idursulfase antibodies during long-term idursulfase enzyme replacement therapy in mucopolysaccharidosis II patients. Mol Genet Metab Rep. 2017 Feb 21;12:2-7. doi: 10.1016/j.ymgmr.2017.01.014. eCollection 2017 Sep.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 14, 2008
• Primary Completion (ACTUAL): February 8, 2013
• Study Completion (ACTUAL): February 8, 2013

Study Registration Dates

• First Submitted: April 16, 2009
• First Submitted That Met QC Criteria: April 16, 2009
• First Posted (ESTIMATE): April 17, 2009

Study Record Updates

• Last Update Posted (ACTUAL): June 8, 2021
• Last Update Submitted That Met QC Criteria: May 14, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: enzyme replacement therapy; Hunter syndrome; lysosomal storage disorder; lysosomal storage disease; MPS 2; mps symptoms; enlarged adenoids; elaprase; hunter's syndrome; MPS2; hunters disease; hunter's disease treatment; hunter syndrome therapy; iduronate sulfatase; mps society; MPSII; hunter syndrome treatment; hunter's disease; iduronate 2 sulfatase; mucopolysaccharides; mps diagnosis; chronic ear infection; hunters syndrome; ert treatment; hunter disease; idursulfase; hunter's syndrome treatment; mps ii therapy; MPS II treatment; mps ii
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; 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; Mucopolysaccharidoses; Syndrome; Mucopolysaccharidosis II
• Other Study ID Numbers: HGT-ELA-042