Clinical trial NCT00069641: Iduronate-2-sulfatase Enzyme Replacement Therapy in Mucopolysaccharidosis II (MPS II)
Official title: A Phase II/III, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Weekly and Every Other Week Dosing Regimens of Iduronate-2-Sulfatase Enzyme Replacement Therapy in Patients With MPS II
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Mucopolysaccharidosis II
Keywords: Mucopolysaccharidosis II
MPS II
Hunter Syndrome
iduronate-2-sulfatase
I2S
Iduronate-2-sulfatase deficiency
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2003-10-01
Enrollment: 96
Sex: MALE
Minimum age (years): 5
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether the administration of iduronate-2-sulfatase enzyme in a weekly or every other week therapy frequency is safe and efficacious in patients with MPS II.

Detailed description: MPS II is a rare, X-linked, lysosomal storage disorder caused by a deficiency in the enzyme iduronate-2-sulfatase. Because of this deficiency, glycosaminoglycans (GAG) accumulate in multiple tissues and organs, resulting in progressive cellular and organ system dysfunction. The purpose of this study is to determine if one year of therapy with iduronate-2-sulfatase enzyme replacement therapy, at a dose of 0.5mg/kg, weekly or every other week, is safe, and results in clinically meaningful improvement in multiple organ function, compared with a placebo group. Upon completion of the study, patients will be eligible to enroll in an open-label maintenance study.

Eligibility criteria: Inclusion Criteria:

To be eligible to participate in this study, patients must meet the following inclusion criteria prior to enrollment:

1. The diagnosis of MPS II will be determined by the investigator based upon both clinical and biochemical criteria.
2. All patients must have at least one of the following Clinical Criteria considered by the investigator to be MPS II-related:

   * Hepatosplenomegaly
   * Radiographic evidence of dysostosis multiplex
   * Valvular heart disease
   * Evidence of obstructive pulmonary disease
3. In addition, patients must have the following Biochemical Criteria:

   * Documented deficiency in iduronate-2-sulfastase enzyme activity of less than or equal to 10% of the lower limit of the normal range as measured in plasma, fibroblasts, or leukocytes (based on normal range of measuring laboratory).
   * A normal enzyme activity level of one other sulfatase as measured in plasma, fibroblasts, or leukocytes (based on normal range of measuring laboratory).
4. Must be male, 5 to 25 years of age.
5. Forced vital capacity of \<80% of predicted obtained at the baseline evaluation of this study.
6. Must be able to adequately perform the testing required in this study, including reproducible pulmonary function testing by spirometry, as judged by the investigator.
7. Patient, patient's parent(s), or 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.

Exclusion Criteria:

Patients meeting any of the following criteria are not eligible for participation in this study:

1. Patient has received treatment with another investigational therapy within the past 60 days.
2. Patient, patient's parent(s), or patient's legal guardian is unable to understand the nature, scope, and possible consequences of the study.
3. Patient is unable to comply with the protocol (e.g., due to a medical condition such as cervical cord compression or uncooperative attitude) or is unlikely to complete the study, as determined by the investigator.
4. Patient has a tracheostomy.
5. Patient has received a bone marrow or cord blood transplant.
6. Patient with known hypersensitivity to any of the components of iduronate-2-sulfatase.

Primary outcomes:
measure: Ranked Adjusted 2-Component Composite Variable Score Based on Change From Baseline to Week 53
timeFrame: Baseline, Week 53
Secondary outcomes:
measure: Change From Baseline in Mean Global Joint Range of Motion (JROM) Score at Week 53
timeFrame: Baseline, Week 53
measure: Mean Combined Liver and Spleen Volume at Baseline
timeFrame: Baseline
measure: Percent Change From Baseline in Mean Combined Liver and Spleen Volume at Week 53
timeFrame: Baseline, Week 53
measure: Change From Baseline in Mean Normalized Urine Glycosaminoglycan (GAG) Levels at Week 53
timeFrame: Baseline, Week 53
measure: Mean Cardiac Left Ventricular Mass Index (LVMI) at Baseline
timeFrame: Baseline
measure: Percent Change From Baseline in Mean Cardiac Left Ventricular Mass Index (LVMI) at Week 53
timeFrame: Baseline, Week 53
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Children's Hospital Oakland
state: California
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital, Washington University
state: Missouri
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Houston
country: United States
facility: Texas Children's Hospital, Baylor College of Medicine
state: Texas
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
city: Mainz
country: Germany
facility: Children's Hospital, Johannes-Gutenburg Universitaet Mainz
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Sick Children
state: England
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
state: England
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Tandon PK, Kakkis ED. The multi-domain responder index: a novel analysis tool to capture a broader assessment of clinical benefit in heterogeneous complex rare diseases. Orphanet J Rare Dis. 2021 Apr 19;16(1):183. doi: 10.1186/s13023-021-01805-5.
citation: Raluy-Callado M, Chen WH, Whiteman DA, Fang J, Wiklund I. The impact of Hunter syndrome (mucopolysaccharidosis type II) on health-related quality of life. Orphanet J Rare Dis. 2013 Jul 10;8:101. doi: 10.1186/1750-1172-8-101.