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

Hunter Syndrome Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00630747
• Other study ID #: TKT024EXT
• Secondary ID: 2004-002743-27
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: September 13, 2004
• Est. completion date: January 31, 2008

Study information

• Verified date: May 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 94
• Est. completion date: January 31, 2008
• Est. primary completion date: January 31, 2008
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 5 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hunter Syndrome
• Mucopolysaccharidoses
• Mucopolysaccharidosis II
• Mucopolysaccharidosis II (MPS II)
• Syndrome

Intervention

Biological:
• Idursulfase
Solution for intravenous infusion, 0.5 mg/kg once-weekly

Locations

Country	Name	City	State
Brazil	Clinica Casa de Saude Sao Joao	Barreiras	BA
Brazil	Hospital Universitario da Faculdade de Medicina da Universidade Federal de Mato Grosso do Sul	Campo Grande	MS
Brazil	Fundacao Universidade de Ciencias da Saude de Alagoas Governador Lamenha Filho / UNCISAL	Maceio	AL
Brazil	Hospital de Clinicas de Porto Alegre, Servico de Genetica Medica	Porto Alegre	RS
Brazil	Instituto de Puericultura e Pediatria Martagao Gesteira / Hospital Pediatrico	Rio de Janeiro	RJ
Brazil	c-HUPES/UFBA	Salvador	BA
Brazil	Instituto da Crianca / Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo	Sao Paulo	SP
Brazil	UNIFESP Instituto de Oncologia Pediatrica	Sao Paulo	SP
Canada	University of Montreal / Hopital Ste-Justine	Montreal	Quebec
Canada	The Hospital for Sick Children Research Institute	Toronto	Ontario
France	Hopital Edouard Herriot	Lyon
France	Hopital de Hautepierre	Strasbourg Cedex
France	Hospital Ducuing	Toulouse Cedex
Germany	Universitatsklinikum Aachen Kinderklinik	Aachen
Germany	Universitatsklinik Dusseldorf Kinderklinik	Dusseldorf
Germany	Justus-Liebig Universitat	Giessen
Germany	Universitatsklinikum Gottingen	Gottingen
Germany	Universitatsklinikum Hamburg Eppendorf	Hamburg
Germany	Children's University Hospital Mainz AG	Mainz
Italy	Universita Milano Bicocca / Ospedale S. Gerardo	Milan
Italy	Universita degli Studi di Napoli Federico II	Napoli
Italy	Universita di Padova	Padova
Italy	Ospedale S. S. Annunziata	Savigliano
Romania	Spitalul Clinic de Copii	Cluj Napoca	Cluj
Spain	University Hospital Germans Trias i Pujol	Badalona
Spain	Servicio de Pediatria	Linares	Jaen
Sweden	Drottning Silvias Barnsjukhus	Gothenberg
Sweden	Karolinska University Hospital	Stockholm
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	Royal Surrey County Hospital	Guildford	Surrey
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 States	Children's Hospital Boston	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	The Children's Hospital	Denver	Colorado
United States	Baylor College of Medicine Texas Children's Hospital	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Franciscan Skemp Healthcare	La Crosse	Wisconsin
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Mid-Illinois Hematology and Oncology Associates	Normal	Illinois
United States	Pediatric Clinical Research Center, Children's Hospital Oakland	Oakland	California
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	St. Joseph's Hospital	Phoenix	Arizona
United States	Harbin Clinic	Rome	Georgia
United States	Saint Louis University Cardinal Glennon Children's Hospital	Saint Louis	Missouri
United States	University of Utah Hospital	Salt Lake City	Utah
United States	Upstate Medical University, State University of New York (SUNY)	Syracuse	New York

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

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

References & Publications (3)

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 ex — View 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. Epub 2006 Dec 20. — View 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. Erratum in: Genet Med. 2006 Sep;8(9):599. Wendt, Suzanne [corrected to Wendt, Susanne]; Puga, Antonio [corrected to Puga, Ana Cristina]; Conway, Ann Marie [corrected to Conway, Anne Marie]. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Change From Baseline in Mean Passive Joint Range of Motion (JROM) at Week 105	Change was 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 Metacarpophalangeal joint (MCP), Proximal interphalangeal joint (PIP), Distal interphalangeal joint (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).	Baseline and at Week 105
Secondary	Change From Baseline in Mean Combined Liver and Spleen Volume at Week 105	Determined by Magnetic Resonance Imaging (MRI). The change was calculated as Week 105 minus baseline.	Baseline and at Week 105
Secondary	Change From Baseline in Mean Normalized Urine Glycosaminoglycans (GAG) Levels at Week 105	Determined by urine testing. The change was calculated as Week 105 minus baseline.	Baseline and at Week 105
Secondary	Change From Baseline in Mean Cardiac Left Ventricular Mass Index (LVMI) at Week 105	Determined by echocardiogram. LVMI indexed to body surface area (g/m^2). The change was calculated as Week 105 minus baseline.	Baseline and at Week 105