Clinical trial NCT00630747: Extension of Study TKT024 Evaluating Long-Term Safety and Clinical Outcomes in MPS II Patients Receiving Idursulfase
Official title: An Open-Label Extension of Study TKT024 Evaluating Long-Term Safety and Clinical Outcomes in MPS II Patients Receiving Iduronate-2-Sulfatase Enzyme Replacement Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Hunter Syndrome
Mucopolysaccharidosis II (MPS II)
Keywords: Hunter syndrome
hunters syndrome
hunter's syndrome
hunter disease
hunters disease
hunter's disease
MPS II
MPSII
MPS2
MPS 2
mucopolysaccharides
lysosomal storage disease
lysosomal storage disorder
chronic ear infection
enlarged adenoids
mps symptoms
mps diagnosis
mps ii therapy
MPS II treatment
ert treatment
elaprase
idursulfase
iduronate sulfatase
iduronate 2 sulfatase
enzyme replacement therapy
hunter syndrome treatment
hunter's syndrome treatment
hunter syndrome therapy
hunter's disease treatment
mps society
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2008-03-07
Enrollment: 94
Sex: MALE
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Study TKT024EXT was a long-term, single-arm, open-label extension of Study TKT024, a one year Phase 2/Phase 3 registration study. The primary objective of this extension study was to collect long-term safety and clinical outcome data in Mucopolysaccharidosis II (MPS II), also known as Hunter Syndrome, from the Phase 2/Phase 3 Study TKT024. All patients enrolling into this study received weekly active treatment with idursulfase, the primary dosing regimen investigated in Study TKT024.

Hunter Syndrome is an X-linked recessive lysosomal storage disease caused by a deficiency of iduronate-2-sulfatase, an enzyme required to catabolize glycosaminoglycans (GAGS) in cells. As a result, GAGs accumulate in the lysosomes leading to cellular engorgement, organomegaly, tissue destruction, and organ system dysfunction. Hunter Syndrome is a rare disease with an estimated incidence of 1 in 162,000 live births.

Detailed description: Study TKT024EXT was conducted in 2 phases. The first phase ("Phase I") was 2 years (104 weeks) in duration and consisted of weekly infusions of IV idursulfase (0.5 mg/kg), and the collection of patients' safety and clinical outcomes. Week 105 defined the beginning of the second phase of the study. The second phase ("Phase II") consisted of weekly infusions of IV idursulfase (0.5 mg/kg) and the monitoring of patients for safety (via collection of adverse events, concomitant medications, and vital signs). Study completion was defined as the time a patient either transitioned to commercially available idursulfase or discontinued this study.

Idursulfase was administered to patients as a continuous IV infusion at a dose of 0.5 mg of protein per kg of body weight (0.5 mg/kg). Final evaluations from Study TKT024, the one-year predecessor Phase 2/Phase 3 registration study, served as the baseline assessments for the TKT024EXT study. Forced vital capacity (FVC) and the 6-minute walk test (6MWT) continued to be the primary clinical outcomes of TKT024EXT study. Efficacy outcomes were evaluated over the course of 2 years and were determined at 4-month intervals during the first year (ie, Weeks 18, 36, and 53) and at 6-month intervals in the second year (ie, Weeks 79 and 105). Safety outcomes were assessed throughout the duration of the study. The safety and clinical testing performed in the TKT024EXT study were identical to those performed in the double-blind phase of Study TKT024.

Eligibility criteria: Inclusion Criteria:

* Patient must have completed the double-blind phase of Study TKT024, defined as completing the Week 53 final evaluations.
* Patient, patient's parent(s), or legally authorized representative 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:

* Patient has received treatment with an investigational therapy other than iduronate-2-sulfatase in Study TKT024 within the past 60 days.
* 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.
* Patient has experienced an adverse reaction to study drug in Study TKT024, which contraindicates further treatment with idursulfase.
* Patient with known hypersensitivity to any of the components of idursulfase.

Primary outcomes:
measure: Change From Baseline in Mean Percent Predicted Forced Vital Capacity (FVC) at Week 105
timeFrame: Baseline and at Week 105
measure: Change From Baseline in Mean Distance Walked in the 6-minute Walk Test (6MWT) at Week 105
timeFrame: Baseline and at Week 105
Secondary outcomes:
measure: Change From Baseline in Mean Passive Joint Range of Motion (JROM) at Week 105
timeFrame: Baseline and at Week 105
measure: Change From Baseline in Mean Combined Liver and Spleen Volume at Week 105
timeFrame: Baseline and at Week 105
measure: Change From Baseline in Mean Normalized Urine Glycosaminoglycans (GAG) Levels at Week 105
timeFrame: Baseline and at Week 105
measure: Change From Baseline in Mean Cardiac Left Ventricular Mass Index (LVMI) at Week 105
timeFrame: Baseline and at Week 105
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: St. Joseph's Hospital
state: Arizona
city: Oakland
country: United States
facility: Pediatric Clinical Research Center, Children's Hospital Oakland
state: California
city: Denver
country: United States
facility: The Children's Hospital
state: Colorado
city: Rome
country: United States
facility: Harbin Clinic
state: Georgia
city: Normal
country: United States
facility: Mid-Illinois Hematology and Oncology Associates
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Saint Louis
country: United States
facility: Saint Louis University Cardinal Glennon Children's Hospital
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Syracuse
country: United States
facility: Upstate Medical University, State University of New York (SUNY)
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine Texas Children's Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: La Crosse
country: United States
facility: Franciscan Skemp Healthcare
state: Wisconsin
city: Maceio
country: Brazil
facility: Fundacao Universidade de Ciencias da Saude de Alagoas Governador Lamenha Filho / UNCISAL
state: AL
city: Barreiras
country: Brazil
facility: Clinica Casa de Saude Sao Joao
state: BA
city: Salvador
country: Brazil
facility: c-HUPES/UFBA
state: BA
city: Campo Grande
country: Brazil
facility: Hospital Universitario da Faculdade de Medicina da Universidade Federal de Mato Grosso do Sul
state: MS
city: Rio de Janeiro
country: Brazil
facility: Instituto de Puericultura e Pediatria Martagao Gesteira / Hospital Pediatrico
state: RJ
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre, Servico de Genetica Medica
state: RS
city: Sao Paulo
country: Brazil
facility: UNIFESP Instituto de Oncologia Pediatrica
state: SP
city: Sao Paulo
country: Brazil
facility: Instituto da Crianca / Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
state: SP
city: Toronto
country: Canada
facility: The Hospital for Sick Children Research Institute
state: Ontario
city: Montreal
country: Canada
facility: University of Montreal / Hopital Ste-Justine
state: Quebec
city: Lyon
country: France
facility: Hopital Edouard Herriot
city: Strasbourg Cedex
country: France
facility: Hopital de Hautepierre
city: Toulouse Cedex
country: France
facility: Hospital Ducuing
city: Aachen
country: Germany
facility: Universitatsklinikum Aachen Kinderklinik
city: Dusseldorf
country: Germany
facility: Universitatsklinik Dusseldorf Kinderklinik
city: Giessen
country: Germany
facility: Justus-Liebig Universitat
city: Gottingen
country: Germany
facility: Universitatsklinikum Gottingen
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg Eppendorf
city: Mainz
country: Germany
facility: Children's University Hospital Mainz AG
city: Milan
country: Italy
facility: Universita Milano Bicocca / Ospedale S. Gerardo
city: Napoli
country: Italy
facility: Universita degli Studi di Napoli Federico II
city: Padova
country: Italy
facility: Universita di Padova
city: Savigliano
country: Italy
facility: Ospedale S. S. Annunziata
city: Cluj Napoca
country: Romania
facility: Spitalul Clinic de Copii
state: Cluj
city: Linares
country: Spain
facility: Servicio de Pediatria
state: Jaen
city: Badalona
country: Spain
facility: University Hospital Germans Trias i Pujol
city: Gothenberg
country: Sweden
facility: Drottning Silvias Barnsjukhus
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
state: Surrey
city: Bath
country: United Kingdom
facility: Bath and NE Somerset Primary Care Trust
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Derby
country: United Kingdom
facility: Derbyshire Children's Hospital
city: Glasgow
country: United Kingdom
facility: Royal Hospital for Sick Children
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Sick Children
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
city: Newcastle
country: United Kingdom
facility: Royal Victoria Infirmary
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Muenzer J, Gucsavas-Calikoglu M, McCandless SE, Schuetz TJ, Kimura A. A phase I/II clinical trial of enzyme replacement therapy in mucopolysaccharidosis II (Hunter syndrome). Mol Genet Metab. 2007 Mar;90(3):329-37. doi: 10.1016/j.ymgme.2006.09.001. Epub 2006 Dec 20.
citation: Muenzer J, Wraith JE, Beck M, Giugliani R, Harmatz P, Eng CM, Vellodi A, Martin R, Ramaswami U, Gucsavas-Calikoglu M, Vijayaraghavan S, Wendt S, Puga AC, Ulbrich B, Shinawi M, Cleary M, Piper D, Conway AM, Kimura A. A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med. 2006 Aug;8(8):465-73. doi: 10.1097/01.gim.0000232477.37660.fb.
citation: Muenzer J, Beck M, Eng CM, Giugliani R, Harmatz P, Martin R, Ramaswami U, Vellodi A, Wraith JE, Cleary M, Gucsavas-Calikoglu M, Puga AC, Shinawi M, Ulbrich B, Vijayaraghavan S, Wendt S, Conway AM, Rossi A, Whiteman DA, Kimura A. Long-term, open-labeled extension study of idursulfase in the treatment of Hunter syndrome. Genet Med. 2011 Feb;13(2):95-101. doi: 10.1097/GIM.0b013e3181fea459.
citation: Beusterien KM, Yeung JE, Pang F, Brazier J. Development of the multi-attribute Adolescent Health Utility Measure (AHUM). Health Qual Life Outcomes. 2012 Aug 28;10:102. doi: 10.1186/1477-7525-10-102.