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

NCT00630747 | Completed Phase 2 Results DMC

• 2 other identifiers: TKT024EXT2004-002743-27
• Study Type: interventional
• Target: 94
• Locations: 10 countries
• Sites: 52

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.

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

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Mean Percent Predicted Forced Vital Capacity (FVC) at Week 105

  Determined by spirometry. The change is calculated as Week 105 minus baseline.

  Baseline and at Week 105

• Change From Baseline in Mean Distance Walked in the 6-minute Walk Test (6MWT) at Week 105

  Determined on a walking course. The change was calculated as Week 105 minus baseline.

  Baseline and at Week 105

Secondary Outcomes (4)

• Change From Baseline in Mean Passive Joint Range of Motion (JROM) at Week 105

  Baseline and at Week 105

• Change From Baseline in Mean Combined Liver and Spleen Volume at Week 105

  Baseline and at Week 105

• Change From Baseline in Mean Normalized Urine Glycosaminoglycans (GAG) Levels at Week 105

  Baseline and at Week 105

• Change From Baseline in Mean Cardiac Left Ventricular Mass Index (LVMI) at Week 105

  Baseline and at Week 105

Study Arms (1)

Idursulfase

EXPERIMENTAL

Biological: Idursulfase

Interventions

Idursulfase BIOLOGICAL

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

Also known as: Elaprase®, iduronate-2-sulfatase

Idursulfase

Eligibility Criteria

• Age: 5 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shire: lead

Study Sites (52)

St. Joseph's Hospital

Phoenix, Arizona, 85013, United States

Location

Pediatric Clinical Research Center, Children's Hospital Oakland

Oakland, California, 94609, United States

Location

The Children's Hospital

Denver, Colorado, 80218, United States

Location

Harbin Clinic

Rome, Georgia, 30165, United States

Location

Mid-Illinois Hematology and Oncology Associates

Normal, Illinois, 61761, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Saint Louis University Cardinal Glennon Children's Hospital

St Louis, Missouri, 63104, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89109, United States

Location

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

Syracuse, New York, 13210, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Baylor College of Medicine Texas Children's Hospital

Houston, Texas, 77030, United States

Location

University of Utah Hospital

Salt Lake City, Utah, 84113, United States

Location

Franciscan Skemp Healthcare

La Crosse, Wisconsin, 54601, United States

Location

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

Maceió, Alagoas, 57010-382, Brazil

Location

Clinica Casa de Saude Sao Joao

Barreiras, Estado de Bahia, 47800-000, Brazil

Location

c-HUPES/UFBA

Salvador, Estado de Bahia, 40110-060, Brazil

Location

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

Campo Grande, Mato Grosso do Sul, 79008-900, Brazil

Location

Instituto de Puericultura e Pediatria Martagao Gesteira / Hospital Pediatrico

Rio de Janeiro, Rio de Janeiro, 21941-590, Brazil

Location

Hospital de Clinicas de Porto Alegre, Servico de Genetica Medica

Porto Alegre, Rio Grande do Sul, 90035-003, Brazil

Location

UNIFESP Instituto de Oncologia Pediatrica

São Paulo, São Paulo, 04023-062, Brazil

Location

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

São Paulo, São Paulo, 05403-000, Brazil

Location

The Hospital for Sick Children Research Institute

Toronto, Ontario, M5G 1XB, Canada

Location

University of Montreal / Hopital Ste-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Hopital Edouard Herriot

Lyon, 69003, France

Location

Hopital de Hautepierre

Strasbourg, 67098, France

Location

Hospital Ducuing

Toulouse, 31076, France

Location

Universitatsklinikum Aachen Kinderklinik

Aachen, D-52074, Germany

Location

Universitatsklinik Dusseldorf Kinderklinik

Düsseldorf, 40225, Germany

Location

Justus-Liebig Universitat

Giessen, 35385, Germany

Location

Universitatsklinikum Gottingen

Göttingen, D-37075, Germany

Location

Universitatsklinikum Hamburg Eppendorf

Hamburg, 20246, Germany

Location

Children's University Hospital Mainz AG

Mainz, 55101, Germany

Location

Universita Milano Bicocca / Ospedale S. Gerardo

Milan, 20052, Italy

Location

Universita degli Studi di Napoli Federico II

Napoli, 80131, Italy

Location

Universita di Padova

Padua, 35121, Italy

Location

Ospedale S. S. Annunziata

Savigliano, 12038, Italy

Location

Spitalul Clinic de Copii

Cluj-Napoca, Cluj, 400370, Romania

Location

Servicio de Pediatria

Linares, Jaen, 23700, Spain

Location

University Hospital Germans Trias i Pujol

Badalona, 08916, Spain

Location

Drottning Silvias Barnsjukhus

Gothenberg, 41685, Sweden

Location

Karolinska University Hospital

Stockholm, 14186, Sweden

Location

Royal Surrey County Hospital

Guildford, Surrey, GU2 5XX, United Kingdom

Location

Bath and NE Somerset Primary Care Trust

Bath, BA1 3QE, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, CB2 2QQ, United Kingdom

Location

Derbyshire Children's Hospital

Derby, DE22 3NE, United Kingdom

Location

Royal Hospital for Sick Children

Glasgow, G3 8SJ, United Kingdom

Location

Great Ormond Street Hospital for Sick Children

London, WC1N3JH, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, M27 4HA, United Kingdom

Location

Royal Victoria Infirmary

Newcastle, NE1 4LP, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 17185020 BACKGROUND

• 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.

  PMID: 16912578 BACKGROUND

• 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.

  PMID: 21150784 RESULT

• 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.

  PMID: 22929184 DERIVED

MeSH Terms

Conditions

Mucopolysaccharidosis II; Sudden Infant Death; Lysosomal Storage Diseases

Interventions

idursulfase; Iduronate Sulfatase

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Death, Sudden; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infant Death

Intervention Hierarchy (Ancestors)

Sulfatases; Esterases; Hydrolases; Enzymes; Enzymes and Coenzymes

Limitations and Caveats

This study design was open-label, and the lack of a concurrently followed placebo group limits the strength of the observations, because the progression of the disease is variable and has not been well described.

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2008
• First Posted: March 7, 2008
• Study Start: September 13, 2004
• Primary Completion: January 31, 2008
• Study Completion: January 31, 2008
• Last Updated: June 10, 2021
• Results First Posted: March 17, 2014

Record last verified: 2021-05

Locations

RO (1); ES (2); BR (8); GB (8); DE (6); SE (2); FR (3); CA (2); IT (4); US (16)