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Mucopolysaccharidosis (MPS)Phase 4NCT05494593

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

A Phase 4 study testing ELAPRASE, Rituximab and Methotrexate in people with Mucopolysaccharidosis (MPS) and Hunter Syndrome, run by Takeda at 8 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages Up to 6 years, men only
Conditions the study is for
Mucopolysaccharidosis (MPS), Hunter Syndrome
What is being tested?
ELAPRASE, Rituximab and Methotrexate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
8 sitesUnited States
Study dates
28 Feb 2023to 29 Aug 2025
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 6 years
  • Men only
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 10Show fewer
  • 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.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Ann and Robert H Lurie Childrens Hospital of Chicago

    Chicago, Illinois, 60611

  • Children's Hospitals and Clinics of Minnesota

    Minneapolis, Minnesota, 55404

  • NewYork-Presbyterian Morgan Stanley Children's Hospital

    New York, New York, 10032

  • Children's Hospital and Research Center at Oakland

    Oakland, California, 94609

  • Phoenix Childrens Hospital

    Phoenix, Arizona, 85016

  • Rady Childrens Hospital San Diego - PIN

    San Diego, California, 92123

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

    Torrance, California, 90502

  • The Cleveland Clinic Foundation

    Twinsburg, Ohio, 44087

Other trials in United States

About this study

Official title: An Open-label, Multicenter, Phase 4 Study to Assess the Effects of a Prophylactic Immune Tolerizing Regimen in MPS II Treatment-Naïve Patients Planned to Receive ELAPRASE Who Are at Risk of Developing Persistent Neutralizing Antibodies

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.

Read more

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).

Being tested
ELAPRASE, Rituximab, Methotrexate, Intravenous Immunoglobulin (IVIG)
Medical subject headings
Mucopolysaccharidoses, Mucopolysaccharidosis II

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ELAPRASEDrug

    Also called Idursulfase

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

  • RituximabDrug

    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.

  • MethotrexateDrug

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

  • Intravenous Immunoglobulin (IVIG)Drug

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

Study groups in NCT05494593
Study groupRoleWhat they receive
ITR + ELAPRASEExperimentalParticipants 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.
Receives: Drug: ELAPRASE; Drug: Rituximab; Drug: Methotrexate; Drug: Intravenous Immunoglobulin (IVIG)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 24 months

Secondary outcomes (4)

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

    Correlation between ADA responses and IDS gene mutations and clinical outcomes (efficacy and safety) every 6 months in comparison to historical results from Study SHPELA- 401 (NCT02455622) without immune tolerance treatment will be reported. Analysis of covariance will be performed to correlate ADA response, IDS gene mutation and clinical outcomes.

    Measured: Every 6 months up to 24 months

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

    Urine samples will be collected for the determination of uGAG levels and urine creatinine monthly prior to dosing. Change from baseline in uGAG levels normalized to urine creatinine will be reported.

    Measured: Up to 24 months

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

    Urine samples will be collected for the determination of uGAG levels monthly prior to dosing. Change from baseline in normalized uGAG/ULN will be reported.

    Measured: Up to 24 months

  4. Change From Baseline in Liver Volume

    Liver volume will be measured using abdominal ultrasonography. Change from baseline values for liver volume will be reported.

    Measured: Up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Aug 2022
  2. Study start28 Feb 2023
  3. Primary completion29 Aug 2025
  4. Study completion29 Aug 2025

Why it stopped: Study was closed due to enrollment challenges

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05494593
Sponsor's protocol ID
TAK-665-4003
Status last verified
Dec 2025
First submitted
8 Aug 2022
Last updated
9 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: De-identified individual participant data from this particular study will not be shared as there is a reasonable likelihood that individual participants could be re-identified (due to the limited number of study participants)

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing ELAPRASE, Rituximab and Methotrexate in people with Mucopolysaccharidosis (MPS) and Hunter Syndrome, run by Takeda at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 9 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of Anti-Idursulfase Antibodies Formation, Including Anti-Idursulfase Antibodies That Have Enzyme Neutralizing Activity (time frame: Up to 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05494593.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2025.

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