Extension of Study TKT024 Evaluating Long-Term Safety and Clinical Outcomes in MPS II Patients Receiving Idursulfase

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire Human Genetic Therapies, Inc.
ClinicalTrials.gov Identifier:
NCT00630747
First received: February 28, 2008
Last updated: January 31, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Hunter Syndrome
Mucopolysaccharidosis II (MPS II)
Biological: Idursulfase
Phase 2
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Shire Human Genetic Therapies, Inc.:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 94
Study Start Date: September 2004
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Idursulfase Biological: Idursulfase
Solution for intravenous infusion, 0.5 mg/kg once-weekly
Other Names:
  • Elaprase®
  • iduronate-2-sulfatase

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

Ages Eligible for Study:   5 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00630747

  Show 52 Study Locations
Sponsors and Collaborators
Shire Human Genetic Therapies, Inc.
Investigators
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
  More Information

Publications:
Responsible Party: Shire Human Genetic Therapies, Inc.
ClinicalTrials.gov Identifier: NCT00630747     History of Changes
Other Study ID Numbers: TKT024EXT
Study First Received: February 28, 2008
Results First Received: February 27, 2012
Last Updated: January 31, 2014
Health Authority: United States: Food and Drug Administration
Brazil: National Health Surveillance Agency
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ministry of Health
Romania: Ministry of Public Health
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Shire Human Genetic Therapies, Inc.:
Hunter syndrome
hunters syndrome
hunter's syndrome
hunter disease
hunters disease
hunter's disease
MPS II
MPSII
MPS2
MPS 2
mps 2
mps ii
mps ii therapy
MPS II therapy
MPS II treatment
iduronate 2 sulfatase
hunter syndrome treatment
hunter's syndrome treatment
hunter syndrome therapy
hunter's disease treatment
mucopolysaccharides
lysosomal storage disease
lysosomal storage disorder
chronic ear infection
enlarged adenoids
mps symptoms
mps diagnosis
ert treatment
elaprase
idursulfase

Additional relevant MeSH terms:
Mucopolysaccharidosis II
Mucopolysaccharidoses
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases
Mental Retardation, X-Linked
Mental Retardation
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Genetic Diseases, X-Linked
Heredodegenerative Disorders, Nervous System

ClinicalTrials.gov processed this record on April 15, 2014