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

NCT ID: NCT00630747

Last Updated: 2021-06-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-09-13
• Study Completion Date: 2008-01-31

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.

Conditions

Hunter Syndrome; Mucopolysaccharidosis II (MPS II)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Idursulfase

Group Type: EXPERIMENTAL

Idursulfase

Intervention Type: BIOLOGICAL

Solution for intravenous infusion, 0.5 mg/kg once-weekly

Interventions

Idursulfase

Solution for intravenous infusion, 0.5 mg/kg once-weekly

Intervention Type: BIOLOGICAL

Other Intervention Names

Elaprase®; iduronate-2-sulfatase

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.

• Minimum Eligible Age: 5 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

St. Joseph's Hospital

Phoenix, Arizona, United States

Pediatric Clinical Research Center, Children's Hospital Oakland

Oakland, California, United States

The Children's Hospital

Denver, Colorado, United States

Harbin Clinic

Rome, Georgia, United States

Mid-Illinois Hematology and Oncology Associates

Normal, Illinois, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Children's Hospital Boston

Boston, Massachusetts, United States

Saint Louis University Cardinal Glennon Children's Hospital

St Louis, Missouri, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Upstate Medical University, State University of New York (SUNY)

Syracuse, New York, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Baylor College of Medicine Texas Children's Hospital

Houston, Texas, United States

University of Utah Hospital

Salt Lake City, Utah, United States

Franciscan Skemp Healthcare

La Crosse, Wisconsin, United States

Fundacao Universidade de Ciencias da Saude de Alagoas Governador Lamenha Filho / UNCISAL

Maceió, Alagoas, Brazil

Clinica Casa de Saude Sao Joao

Barreiras, Estado de Bahia, Brazil

c-HUPES/UFBA

Salvador, Estado de Bahia, Brazil

Hospital Universitario da Faculdade de Medicina da Universidade Federal de Mato Grosso do Sul

Campo Grande, Mato Grosso do Sul, Brazil

Instituto de Puericultura e Pediatria Martagao Gesteira / Hospital Pediatrico

Rio de Janeiro, Rio de Janeiro, Brazil

Hospital de Clinicas de Porto Alegre, Servico de Genetica Medica

Porto Alegre, Rio Grande do Sul, Brazil

UNIFESP Instituto de Oncologia Pediatrica

São Paulo, São Paulo, Brazil

Instituto da Crianca / Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo

São Paulo, São Paulo, Brazil

The Hospital for Sick Children Research Institute

Toronto, Ontario, Canada

University of Montreal / Hopital Ste-Justine

Montreal, Quebec, Canada

Hopital Edouard Herriot

Lyon, , France

Hopital de Hautepierre

Strasbourg, , France

Hospital Ducuing

Toulouse, , France

Universitatsklinikum Aachen Kinderklinik

Aachen, , Germany

Universitatsklinik Dusseldorf Kinderklinik

Düsseldorf, , Germany

Justus-Liebig Universitat

Giessen, , Germany

Universitatsklinikum Gottingen

Göttingen, , Germany

Universitatsklinikum Hamburg Eppendorf

Hamburg, , Germany

Children's University Hospital Mainz AG

Mainz, , Germany

Universita Milano Bicocca / Ospedale S. Gerardo

Milan, , Italy

Universita degli Studi di Napoli Federico II

Napoli, , Italy

Universita di Padova

Padua, , Italy

Ospedale S. S. Annunziata

Savigliano, , Italy

Spitalul Clinic de Copii

Cluj-Napoca, Cluj, Romania

Servicio de Pediatria

Linares, Jaen, Spain

University Hospital Germans Trias i Pujol

Badalona, , Spain

Drottning Silvias Barnsjukhus

Gothenberg, , Sweden

Karolinska University Hospital

Stockholm, , Sweden

Royal Surrey County Hospital

Guildford, Surrey, United Kingdom

Bath and NE Somerset Primary Care Trust

Bath, , United Kingdom

Addenbrooke's Hospital

Cambridge, , United Kingdom

Derbyshire Children's Hospital

Derby, , United Kingdom

Royal Hospital for Sick Children

Glasgow, , United Kingdom

Great Ormond Street Hospital for Sick Children

London, , United Kingdom

Royal Manchester Children's Hospital

Manchester, , United Kingdom

Royal Victoria Infirmary

Newcastle, , United Kingdom

Countries

United States; Brazil; Canada; France; Germany; Italy; Romania; Spain; Sweden; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 17185020 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16912578 (View on PubMed)

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.

Reference Type: RESULT

PMID: 21150784 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22929184 (View on PubMed)

Other Identifiers

2004-002743-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TKT024EXT

Identifier Type: -

Identifier Source: org_study_id