Back to resultsA Study of ELAPRASE in Treatment-naïve Participants With Hunter Syndrome (Mucopolysaccharidosis [MPS] II)
Primary Purpose
Mucopolysaccharidosis (MPS), Hunter Syndrome
Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
ELAPRASE
Rituximab
Methotrexate
Intravenous Immunoglobulin (IVIG)
Sponsored by
About this trial
This is an interventional treatment trial for Mucopolysaccharidosis (MPS)
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.
Sites / Locations
- Phoenix Childrens HospitalRecruiting
- Children's Hospital and Research Center at OaklandRecruiting
- UC Davis Medical Center
- Rady Childrens Hospital San Diego - PINRecruiting
- The Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical CenterRecruiting
- Ann and Robert H Lurie Childrens Hospital of Chicago
- Children's Hospitals and Clinics of MinnesotaRecruiting
- NewYork-Presbyterian Morgan Stanley Children's Hospital
- University of North Carolina at Chapel Hill
- The Cleveland Clinic Foundation
- Children's Hospital of Pittsburgh
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ITR + ELAPRASE
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
Change From Baseline in Liver Volume
Liver volume will be measured using abdominal ultrasonography. Change from baseline values for liver volume will be reported.
Full Information
NCT ID
NCT05494593
First Posted
August 8, 2022
Last Updated
September 21, 2023
Sponsor
Takeda
Collaborators
Takeda Development Center Americas, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05494593
Brief Title
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
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 28, 2023 (Actual)
Primary Completion Date
June 15, 2027 (Anticipated)
Study Completion Date
June 15, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
Collaborators
Takeda Development Center Americas, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mucopolysaccharidosis (MPS), Hunter Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ITR + ELAPRASE
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
ELAPRASE
Other Intervention Name(s)
Idursulfase
Intervention Description
Participants will receive 0.5 milligram per kilogram (mg/kg) of body weight of ELAPRASE, intravenous, infusion for 104 weeks.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
Participants will receive 0.4 mg/kg of methotrexate by mouth (PO) 3 times per week for 5 weeks in each cycle.
Intervention Type
Drug
Intervention Name(s)
Intravenous Immunoglobulin (IVIG)
Intervention Description
Participants will receive 500 mg/kg of IVIG every 4 weeks in 5-week cycle.
Primary Outcome Measure Information:
Title
Rate of Anti-Idursulfase Antibodies Formation, Including Anti-Idursulfase Antibodies That Have Enzyme Neutralizing Activity
Description
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.
Time Frame
Up to 24 months
Secondary Outcome Measure Information:
Title
Correlation Between Anti-drug Antibody (ADA) Responses and Iduronate-2-Sulfatase (IDS) Gene Mutations and Clinical Outcomes
Description
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.
Time Frame
Every 6 months up to 24 months
Title
Change From Baseline in Urinary Glycosaminoglycan (uGAG) Levels Normalized to Urine Creatinine
Description
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.
Time Frame
Up to 24 months
Title
Change From Baseline in Normalized uGAG per Upper Limit of Normal for age (uGAG)/ULN)
Description
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.
Time Frame
Up to 24 months
Title
Change From Baseline in Liver Volume
Description
Liver volume will be measured using abdominal ultrasonography. Change from baseline values for liver volume will be reported.
Time Frame
Up to 24 months
10. Eligibility
Sex
Male
Maximum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Takeda Contact
Phone
+1-877-825-3327
Email
medinfoUS@takeda.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Phoenix Childrens Hospital
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
First Name & Middle Initial & Last Name & Degree
Gerard Vockley
Facility Name
Children's Hospital and Research Center at Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
510-428-3058
Email
paul.harmatz@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Paul Harmatz
Facility Name
UC Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
916-703-0346
Email
bcgmartin@ucdavis.edu
First Name & Middle Initial & Last Name & Degree
Madelena Martin
Facility Name
Rady Childrens Hospital San Diego - PIN
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
858-966-8508
Email
rmardach@health.ucsd.edu
First Name & Middle Initial & Last Name & Degree
Rebecca Mardach
Facility Name
The Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical Center
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
310-222-1961
Email
lpolgreen@labiomed.org
First Name & Middle Initial & Last Name & Degree
Lynda Polgreen
Facility Name
Ann and Robert H Lurie Childrens Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
312-227-6120
Email
bburton@luriechildrens.org
First Name & Middle Initial & Last Name & Degree
Barbara Burton
Facility Name
Children's Hospitals and Clinics of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
612-813-7240
Email
vikas.bhambhani@childrensmn.org
First Name & Middle Initial & Last Name & Degree
Vikas Bhambhani
Facility Name
NewYork-Presbyterian Morgan Stanley Children's Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
212-305-3647
Email
gm3025@cumc.columbia.edu
First Name & Middle Initial & Last Name & Degree
Gustavo Maegawa
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
919-966-1447
Email
muenzer@med.unc.edu
First Name & Middle Initial & Last Name & Degree
Joseph Muenzer
Facility Name
The Cleveland Clinic Foundation
City
Twinsburg
State/Province
Ohio
ZIP/Postal Code
44087
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
216-445-7862
Email
hannar2@ccf.org
First Name & Middle Initial & Last Name & Degree
Rabi Hanna
Facility Name
Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
412-692-5194
Email
damara.ortiz@chp.edu
First Name & Middle Initial & Last Name & Degree
Damara Ortiz
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
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)
Links:
URL
https://clinicaltrials.takeda.com/study-detail/15c973b2efde4ff6?idFilter=%5B%22TAK-665-4003%22%5D
Description
To obtain more information on the study, click here/on this link
Learn more about this trial
A Study of ELAPRASE in Treatment-naïve Participants With Hunter Syndrome (Mucopolysaccharidosis [MPS] II)
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