Extension of Study TKT024 Evaluating Long-Term Safety and Clinical Outcomes in MPS II Patients Receiving Idursulfase
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.
Mucopolysaccharidosis II (MPS II)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- Change From Baseline in Mean Percent Predicted Forced Vital Capacity (FVC) at Week 105 [ Time Frame: Baseline and at Week 105 ] [ Designated as safety issue: No ]Determined by spirometry. The change is calculated as Week 105 minus baseline.
- Change From Baseline in Mean Distance Walked in the 6-minute Walk Test (6MWT) at Week 105 [ Time Frame: Baseline and at Week 105 ] [ Designated as safety issue: No ]Determined on a walking course. The change is calculated as Week 105 minus baseline.
- Change From Baseline in Mean Passive Joint Range of Motion (JROM) at Week 105 [ Time Frame: Baseline and at Week 105 ] [ Designated as safety issue: No ]Change is calculated as Week 105 minus baseline. Global JROM (% normal range of motion) is the average of 11 ratios multiplied by 100. Ratios are Left/Right means of passive range of motion in Shoulder (Flexion/Extension, Abduction, Internal/External Rotation), Elbow (Flexion/Extension), Wrist (Flexion/Extension), Index Finger (Flexion/Extension [Combined MCP, PIP, DIP motion]), Hip (Flexion/Extension, Abduction, Internal/External Rotation), Knee (Flexion/Extension), and Ankle (Dorsiflexion) divided by the normal range (American Academy of Orthopedic Surgeons and American Medical Association).
- Change From Baseline in Mean Combined Liver and Spleen Volume at Week 105 [ Time Frame: Baseline and at Week 105 ] [ Designated as safety issue: No ]Determined by Magnetic Resonance Imaging (MRI). The change is calculated as Week 105 minus baseline.
- Change From Baseline in Mean Normalized Urine Glycosaminoglycans (GAG) Levels at Week 105 [ Time Frame: Baseline and at Week 105 ] [ Designated as safety issue: No ]Determined by urine testing. The change is calculated as Week 105 minus baseline.
- Change From Baseline in Mean Cardiac Left Ventricular Mass Index (LVMI) at Week 105 [ Time Frame: Baseline and at Week 105 ] [ Designated as safety issue: No ]Determined by echocardiogram. LVMI indexed to body surface area (g/m^2). The change is calculated as Week 105 minus baseline.
|Study Start Date:||September 2004|
|Study Completion Date:||January 2008|
|Primary Completion Date:||January 2008 (Final data collection date for primary outcome measure)|
Solution for intravenous infusion, 0.5 mg/kg once-weekly
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.
Show 52 Study Locations
|Principal Investigator:||Joseph Muenzer, MD, PhD||University of North Carolina, Chapel Hill|
|Principal Investigator:||Kirk Aleck, MD||St. Joseph's Hospital|
|Principal Investigator:||Roberto Giugliani, MD||Hospital de Clinicas de Porto Alegre, Servico de Genetica Medica|
|Principal Investigator:||Michael Beck, MD||Children's University Hospital Mainz AG|
|Principal Investigator:||Uma Ramaswami, MD||Cambridge University Hospitals NHS Foundation Trust|
|Principal Investigator:||Ashok Vellodi, MD||Great Ormond Street Hospital for Sick Children|
|Principal Investigator:||J. Edmond Wraith, MRCP, FRCP||Royal Manchester Children's Hospital|
|Principal Investigator:||Paul Harmatz, MD||Pediatric Clinical Research Center, Children's Hospital Oakland|
|Principal Investigator:||Rick Martin, MD||Saint Louis University Cardinal Glennon Children's Hospital|
|Principal Investigator:||Christine Eng, MD||Baylor College of Medicine Texas Children's Hospital|
|Principal Investigator:||Ana Maria Martins, MD||UNIFESP Instituto de Oncologia Pediatrica|
|Principal Investigator:||Angelina Acosta, MD||c-HUPES/UFBA|
|Principal Investigator:||Chong Kim, MD||Instituto da Crianca / Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo|
|Principal Investigator:||Durval Batista Palhares, MD||Hospital Universitario da Faculdade de Medicina da Universidade Federal de Mato Grosso do Sul|
|Principal Investigator:||Emerson Santos, MD||Fundacao Universidade de Ciencias da Saude de Alagoas Governador Lamenha Filho / UNCISAL|
|Principal Investigator:||Marcia Ribeiro, MD||Instituto de Puericultura e Pediatria Martagao Gesteira / Hospital Pediatrico|
|Principal Investigator:||Roberto Garcia De Lima, MD||Clinica Casa de Saude Sao Joao|
|Principal Investigator:||Emmanuelle Lemyre, MD||University of Montreal / Hopital Ste-Justine|
|Principal Investigator:||Joe Clarke, MD||The Hospital for Sick Children Research Institute|
|Principal Investigator:||Nathalie Guffon, MD||Hopital Edouard Herriot|
|Principal Investigator:||Michel Fischbach, MD||HOPITAL DE HAUTEPIERRE|
|Principal Investigator:||Francis Gaches, MD||Hospital Ducuing|
|Principal Investigator:||Rolf Mertens, MD||Universitatsklinikum Aachen Kinderklinik|
|Principal Investigator:||Bjorn Hoffmann, MD||Universitatsklinik Dusseldorf Kinderklinik|
|Principal Investigator:||Robert Steinfeld, MD, PhD||Universitatsklinikum Gottingen|
|Principal Investigator:||Joachim Kreuder, MD||Justus-Liebig Universitat|
|Principal Investigator:||Kurt Ullrich, MD||Universitatsklinikum Hamburg Eppendorf|
|Principal Investigator:||Luigi Besenzon, MD||Ospedale S. S. Annunziata|
|Principal Investigator:||Maurizio Scarpa, MD||Universita di Padova|
|Principal Investigator:||Rossella Parini, MD||Universita Milano Bicocca / Ospedale S. Gerardo|
|Principal Investigator:||Generoso Andria, MD||Universita degli Studi di Napoli Federico II|
|Principal Investigator:||Paula Grigorescu Sido, MD||Spitalul Clinic de Copii|
|Principal Investigator:||Guillem Pintos-Morell, MD||University Hospital Germans Trias i Pujol|
|Principal Investigator:||Antonia Patrocinio Leon Asensio, MD||Servicio de Pediatria|
|Principal Investigator:||Pilar Munguira Aguado, MD||Servicio de Pediatria|
|Principal Investigator:||Paul Uvebrant, MD||Drottning Silvias Barnsjukhus|
|Principal Investigator:||Gunilla Malm, MD||Karolinska University Hospital|
|Principal Investigator:||Mal Ratnayaka, MD||Derbyshire Children's Hospital|
|Principal Investigator:||Peter H. Robinson, MD||Royal Hospital for Sick Children|
|Principal Investigator:||Michael Ryalls, MD||Royal Surrey County Hospital|
|Principal Investigator:||Nicola Leech, MD||Royal Victoria Infirmary|
|Principal Investigator:||Stuart Murray, MD||Bath and NE Somerset Primary Care Trust|
|Principal Investigator:||Janet Thomas, MD||The Children's Hospital|
|Principal Investigator:||Sara Copeland, MD||University of Iowa|
|Principal Investigator:||Hwan Jeong, MD||Mid-Illinois Hematology and Oncology Associates|
|Principal Investigator:||Ronald Kline, MD||Comprehensive Cancer Centers of Nevada|
|Principal Investigator:||Edward Neilan, MD||Children's Hospital Boston|
|Principal Investigator:||G. Bradley Schaefer, MD||University of Nebraska|
|Principal Investigator:||Paige Kaplan, MD||Children's Hospital of Philadelphia|
|Principal Investigator:||Dilip Patel, MD||Harbin Clinic|
|Principal Investigator:||Dave Viskochil, MD||University of Utah Hospital|
|Principal Investigator:||Irene Cherrick, MD||Upstate Medical University, State University of New York (SUNY)|
|Principal Investigator:||David Capelli, MD||Franciscan Skemp Healthcare|