A Study of ELAPRASE in Treatment-naïve Participants With Hunter Syndrome (Mucopolysaccharidosis [MPS] II)

NCT05494593 | Withdrawn Phase 4 DMC FDA Drug

• 1 other identifier: TAK-665-4003
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 8

Brief Summary

The main aim of this study is to evaluate the ability of a prophylactic immune tolerizing regimen (ITR) to prevent or reduce the development of high titer anti-idursulfase antibodies in treatment-naïve participants with Hunter syndrome. In this open label, single arm study, all participants will receive ELAPRASE treatment and a prophylactic ITR. Participants will be treated with ELAPRASE for up to 104 weeks. The prophylactic ITR will start 1 day prior to the start of ELAPRASE. The prophylactic ITR will consist of a 5-week cycle of: Rituximab (intravenously \[IV\], weekly for 4 weeks); Methotrexate (oral, 3 times per week for 5 weeks) and intravenous immunoglobulin (IVIG) (IV, every 4 weeks of the cycle). Following the completion of 1 cycle, an assessment will be made at Month 6, 12, and 18 regarding the need for administering another 5-week cycle of the ITR. Participants will be in the study for approximately 112 weeks (including 6 weeks for screening, up to 104 weeks for treatment, and 2 weeks for follow-up).

Conditions

Mucopolysaccharidosis (MPS); Hunter Syndrome

Outcome Measures

Primary Outcomes (1)

• Rate of Anti-Idursulfase Antibodies Formation, Including Anti-Idursulfase Antibodies That Have Enzyme Neutralizing Activity

  Serum samples will be collected for evaluation of anti-idursulfase antibodies including binding antibodies and neutralizing antibodies. Analysis of anti-idursulfase antibodies will be conducted using validated 3-tier immunoassay methods. Rate will be defined as the number of participants having positive antibodies compared to the total number of participants.

  Up to 24 months

Secondary Outcomes (4)

• Correlation Between Anti-drug Antibody (ADA) Responses and Iduronate-2-Sulfatase (IDS) Gene Mutations and Clinical Outcomes

  Every 6 months up to 24 months

• Change From Baseline in Urinary Glycosaminoglycan (uGAG) Levels Normalized to Urine Creatinine

  Up to 24 months

• Change From Baseline in Normalized uGAG per Upper Limit of Normal for age (uGAG)/ULN)

  Up to 24 months

• Change From Baseline in Liver Volume

  Up to 24 months

Study Arms (1)

ITR + ELAPRASE

EXPERIMENTAL

Participants will receive prophylactic ITR which consist of rituximab, methotrexate and IVIG in a 5-week cycle. Following the completion of 1 cycle and at the Month 6, 12, and 18 study visits, an assessment will be made regarding the need for administering another 5-week cycle of the ITR depending on the trend of the participants anti-idursulfase antibody titers and lymphocyte quantitation and CD19 percent (%) recovery. Elaprase treatment (IV, weekly) will start 1 day after the initiation of the first cycle of ITR and continue for 104 weeks. The dose of ELAPRASE will be calculated based on the participant's weight at each visit.

Drug: ELAPRASE; Drug: Rituximab; Drug: Methotrexate; Drug: Intravenous Immunoglobulin (IVIG)

Interventions

ELAPRASE DRUG

Participants will receive 0.5 milligram per kilogram (mg/kg) of body weight of ELAPRASE, intravenous, infusion for 104 weeks.

Also known as: Idursulfase

ITR + ELAPRASE

Rituximab DRUG

Participants will receive 375 milligram per square meter per dose (mg/m\^2/dose) of intravenous rituximab weekly for 4 weeks in 5-week cycle.

ITR + ELAPRASE

Methotrexate DRUG

Participants will receive 0.4 mg/kg of methotrexate by mouth (PO) 3 times per week for 5 weeks in each cycle.

ITR + ELAPRASE

Intravenous Immunoglobulin (IVIG) DRUG

Participants will receive 500 mg/kg of IVIG every 4 weeks in 5-week cycle.

ITR + ELAPRASE

Eligibility Criteria

• Age: Up to 6 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participant is male.
• Participant is ELAPRASE-naïve at study entry.
• Participant must have a documented diagnosis of MPS II. The following combination will be accepted as diagnostic of MPS II:
• Participant has a deficiency in iduronate-2-sulfatase (I2S) enzyme activity of less than or equal to (\<=) 10 percent (%) of the lower limit of the normal range as measured in plasma, fibroblasts, or leukocytes (based on the reference laboratory's normal range). The participant has a normal enzyme activity level of at least 1 other sulfatase as measured in plasma, fibroblasts, or leukocytes (based on the reference laboratory's normal range).
• Participant has a documented mutation in the IDS gene; additionally, participants must have a severe mutation (example, large deletion or complex gene rearrangement), which is predicted to lead to development of a persistent anti-idursulfase antibody response.
• Participant will be less than (\<) 6 years of age at enrollment.
• Participant has a negative test result for serum anti-idursulfase antibodies.

You may not qualify if:

• Participant has received treatment with any investigational drug within the 30 days prior to study entry.
• Participant has received or is receiving treatment with idursulfase-IT.
• Participant has received growth hormones, a cord blood infusion, or a bone marrow transplant at any time.
• Participant has received blood product transfusions within 90 days prior to screening.
• Participant is unable to comply with the protocol as determined by the investigator.
• Participant has known or suspected intolerance or hypersensitivity to the investigational product(s), closely related compounds, or any of the stated ingredients, including the prophylactic ITR.
• Participant has current or recurrent disease that could affect the action, absorption, or disposition of the investigational product, or clinical or laboratory assessments.
• Participant has current or relevant history of physical or psychiatric illness, or any medical disorder that may require treatment or make the participant unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures.
• Participant has current use of any medication (including over-the-counter, herbal, or homeopathic preparations) that could affect (improve or worsen) the condition being studied, or could affect the action, absorption, or disposition of the investigational product(s), or clinical or laboratory assessment (Current use is defined as use within 30 days).
• Within 30 days prior to the first dose of investigational product, the participant has been enrolled in a clinical study (including vaccine studies) that, in the investigator's opinion, may impact this study.

Sponsors & Collaborators

• Takeda: lead
• Takeda Development Center Americas, Inc.: collaborator

Study Sites (8)

Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States

Location

Children's Hospital and Research Center at Oakland

Oakland, California, 94609, United States

Location

Rady Childrens Hospital San Diego - PIN

San Diego, California, 92123, United States

Location

The Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

Ann and Robert H Lurie Childrens Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Children's Hospitals and Clinics of Minnesota

Minneapolis, Minnesota, 55404, United States

Location

NewYork-Presbyterian Morgan Stanley Children's Hospital

New York, New York, 10032, United States

Location

The Cleveland Clinic Foundation

Twinsburg, Ohio, 44087, United States

Location

Related Links

• To obtain more information on the study, click here/on this link

MeSH Terms

Conditions

Mucopolysaccharidoses; Mucopolysaccharidosis II

Interventions

idursulfase; Rituximab; Methotrexate; Immunoglobulins, Intravenous

Condition Hierarchy (Ancestors)

Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Immunoglobulin G; Immunoglobulin Isotypes

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2022
• First Posted: August 10, 2022
• Study Start: February 28, 2023
• Primary Completion: August 29, 2025
• Study Completion: August 29, 2025
• Last Updated: December 9, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)