Clinical trial NCT05494593: A Study of ELAPRASE in Treatment-naïve Participants With Hunter Syndrome (Mucopolysaccharidosis [MPS] II)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Mucopolysaccharidosis (MPS)
Hunter Syndrome
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Takeda Development Center Americas, Inc.
First posted: 2022-08-10
Enrollment: 5
Sex: MALE
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Rate of Anti-Idursulfase Antibodies Formation, Including Anti-Idursulfase Antibodies That Have Enzyme Neutralizing Activity
timeFrame: Up to 24 months
Secondary outcomes:
measure: Correlation Between Anti-drug Antibody (ADA) Responses and Iduronate-2-Sulfatase (IDS) Gene Mutations and Clinical Outcomes
timeFrame: Every 6 months up to 24 months
measure: Change From Baseline in Urinary Glycosaminoglycan (uGAG) Levels Normalized to Urine Creatinine
timeFrame: Up to 24 months
measure: Change From Baseline in Normalized uGAG per Upper Limit of Normal for age (uGAG)/ULN)
timeFrame: Up to 24 months
measure: Change From Baseline in Liver Volume
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital
state: Arizona
city: Oakland
country: United States
facility: Children's Hospital and Research Center at Oakland
state: California
city: San Diego
country: United States
facility: Rady Childrens Hospital San Diego - PIN
state: California
city: Torrance
country: United States
facility: The Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical Center
state: California
city: Chicago
country: United States
facility: Ann and Robert H Lurie Childrens Hospital of Chicago
state: Illinois
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota
state: Minnesota
city: New York
country: United States
facility: NewYork-Presbyterian Morgan Stanley Children's Hospital
state: New York
city: Twinsburg
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: