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

Primary Purpose

Hunter Syndrome, Mucopolysaccharidosis II (MPS II)

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Idursulfase
Sponsored by
Shire
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hunter Syndrome focused on measuring 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

Eligibility Criteria

5 Years - undefined (Child, Adult, Older Adult)MaleDoes not accept healthy volunteers

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.

Sites / Locations

  • St. Joseph's Hospital
  • Pediatric Clinical Research Center, Children's Hospital Oakland
  • The Children's Hospital
  • Harbin Clinic
  • Mid-Illinois Hematology and Oncology Associates
  • University of Iowa Hospitals and Clinics
  • Children's Hospital Boston
  • Saint Louis University Cardinal Glennon Children's Hospital
  • University of Nebraska Medical Center
  • Comprehensive Cancer Centers of Nevada
  • Upstate Medical University, State University of New York (SUNY)
  • University of North Carolina at Chapel Hill
  • Children's Hospital of Philadelphia
  • Baylor College of Medicine Texas Children's Hospital
  • University of Utah Hospital
  • Franciscan Skemp Healthcare
  • Fundacao Universidade de Ciencias da Saude de Alagoas Governador Lamenha Filho / UNCISAL
  • Clinica Casa de Saude Sao Joao
  • c-HUPES/UFBA
  • Hospital Universitario da Faculdade de Medicina da Universidade Federal de Mato Grosso do Sul
  • Instituto de Puericultura e Pediatria Martagao Gesteira / Hospital Pediatrico
  • Hospital de Clinicas de Porto Alegre, Servico de Genetica Medica
  • UNIFESP Instituto de Oncologia Pediatrica
  • Instituto da Crianca / Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
  • The Hospital for Sick Children Research Institute
  • University of Montreal / Hopital Ste-Justine
  • Hopital Edouard Herriot
  • Hopital de Hautepierre
  • Hospital Ducuing
  • Universitatsklinikum Aachen Kinderklinik
  • Universitatsklinik Dusseldorf Kinderklinik
  • Justus-Liebig Universitat
  • Universitatsklinikum Gottingen
  • Universitatsklinikum Hamburg Eppendorf
  • Children's University Hospital Mainz AG
  • Universita Milano Bicocca / Ospedale S. Gerardo
  • Universita degli Studi di Napoli Federico II
  • Universita di Padova
  • Ospedale S. S. Annunziata
  • Spitalul Clinic de Copii
  • Servicio de Pediatria
  • University Hospital Germans Trias i Pujol
  • Drottning Silvias Barnsjukhus
  • Karolinska University Hospital
  • Royal Surrey County Hospital
  • Bath and NE Somerset Primary Care Trust
  • Addenbrooke's Hospital
  • Derbyshire Children's Hospital
  • Royal Hospital for Sick Children
  • Great Ormond Street Hospital for Sick Children
  • Royal Manchester Children's Hospital
  • Royal Victoria Infirmary

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Idursulfase

Arm Description

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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).
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.
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.
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.

Full Information

First Posted
February 28, 2008
Last Updated
May 26, 2021
Sponsor
Shire
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1. Study Identification

Unique Protocol Identification Number
NCT00630747
Brief Title
Extension of Study TKT024 Evaluating Long-Term Safety and Clinical Outcomes in MPS II Patients Receiving Idursulfase
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
September 13, 2004 (Actual)
Primary Completion Date
January 31, 2008 (Actual)
Study Completion Date
January 31, 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shire

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
94 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Idursulfase
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Idursulfase
Other Intervention Name(s)
Elaprase®, iduronate-2-sulfatase
Intervention Description
Solution for intravenous infusion, 0.5 mg/kg once-weekly
Primary Outcome Measure Information:
Title
Change From Baseline in Mean Percent Predicted Forced Vital Capacity (FVC) at Week 105
Description
Determined by spirometry. The change is calculated as Week 105 minus baseline.
Time Frame
Baseline and at Week 105
Title
Change From Baseline in Mean Distance Walked in the 6-minute Walk Test (6MWT) at Week 105
Description
Determined on a walking course. The change was calculated as Week 105 minus baseline.
Time Frame
Baseline and at Week 105
Secondary Outcome Measure Information:
Title
Change From Baseline in Mean Passive Joint Range of Motion (JROM) at Week 105
Description
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).
Time Frame
Baseline and at Week 105
Title
Change From Baseline in Mean Combined Liver and Spleen Volume at Week 105
Description
Determined by Magnetic Resonance Imaging (MRI). The change was calculated as Week 105 minus baseline.
Time Frame
Baseline and at Week 105
Title
Change From Baseline in Mean Normalized Urine Glycosaminoglycans (GAG) Levels at Week 105
Description
Determined by urine testing. The change was calculated as Week 105 minus baseline.
Time Frame
Baseline and at Week 105
Title
Change From Baseline in Mean Cardiac Left Ventricular Mass Index (LVMI) at Week 105
Description
Determined by echocardiogram. LVMI indexed to body surface area (g/m^2). The change was calculated as Week 105 minus baseline.
Time Frame
Baseline and at Week 105

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
5 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
St. Joseph's Hospital
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
Pediatric Clinical Research Center, Children's Hospital Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
The Children's Hospital
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Harbin Clinic
City
Rome
State/Province
Georgia
ZIP/Postal Code
30165
Country
United States
Facility Name
Mid-Illinois Hematology and Oncology Associates
City
Normal
State/Province
Illinois
ZIP/Postal Code
61761
Country
United States
Facility Name
University of Iowa Hospitals and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Children's Hospital Boston
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Saint Louis University Cardinal Glennon Children's Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89109
Country
United States
Facility Name
Upstate Medical University, State University of New York (SUNY)
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Baylor College of Medicine Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States
Facility Name
Franciscan Skemp Healthcare
City
La Crosse
State/Province
Wisconsin
ZIP/Postal Code
54601
Country
United States
Facility Name
Fundacao Universidade de Ciencias da Saude de Alagoas Governador Lamenha Filho / UNCISAL
City
Maceio
State/Province
AL
ZIP/Postal Code
57010-382
Country
Brazil
Facility Name
Clinica Casa de Saude Sao Joao
City
Barreiras
State/Province
BA
ZIP/Postal Code
47800-000
Country
Brazil
Facility Name
c-HUPES/UFBA
City
Salvador
State/Province
BA
ZIP/Postal Code
40110-060
Country
Brazil
Facility Name
Hospital Universitario da Faculdade de Medicina da Universidade Federal de Mato Grosso do Sul
City
Campo Grande
State/Province
MS
ZIP/Postal Code
79008-900
Country
Brazil
Facility Name
Instituto de Puericultura e Pediatria Martagao Gesteira / Hospital Pediatrico
City
Rio de Janeiro
State/Province
RJ
ZIP/Postal Code
21941-590
Country
Brazil
Facility Name
Hospital de Clinicas de Porto Alegre, Servico de Genetica Medica
City
Porto Alegre
State/Province
RS
ZIP/Postal Code
90035-003
Country
Brazil
Facility Name
UNIFESP Instituto de Oncologia Pediatrica
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
04023-062
Country
Brazil
Facility Name
Instituto da Crianca / Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
05403-000
Country
Brazil
Facility Name
The Hospital for Sick Children Research Institute
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1XB
Country
Canada
Facility Name
University of Montreal / Hopital Ste-Justine
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1C5
Country
Canada
Facility Name
Hopital Edouard Herriot
City
Lyon
ZIP/Postal Code
69003
Country
France
Facility Name
Hopital de Hautepierre
City
Strasbourg Cedex
ZIP/Postal Code
67098
Country
France
Facility Name
Hospital Ducuing
City
Toulouse Cedex
ZIP/Postal Code
31076
Country
France
Facility Name
Universitatsklinikum Aachen Kinderklinik
City
Aachen
ZIP/Postal Code
D-52074
Country
Germany
Facility Name
Universitatsklinik Dusseldorf Kinderklinik
City
Dusseldorf
ZIP/Postal Code
40225
Country
Germany
Facility Name
Justus-Liebig Universitat
City
Giessen
ZIP/Postal Code
35385
Country
Germany
Facility Name
Universitatsklinikum Gottingen
City
Gottingen
ZIP/Postal Code
D-37075
Country
Germany
Facility Name
Universitatsklinikum Hamburg Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Children's University Hospital Mainz AG
City
Mainz
ZIP/Postal Code
55101
Country
Germany
Facility Name
Universita Milano Bicocca / Ospedale S. Gerardo
City
Milan
ZIP/Postal Code
20052
Country
Italy
Facility Name
Universita degli Studi di Napoli Federico II
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Universita di Padova
City
Padova
ZIP/Postal Code
35121
Country
Italy
Facility Name
Ospedale S. S. Annunziata
City
Savigliano
ZIP/Postal Code
12038
Country
Italy
Facility Name
Spitalul Clinic de Copii
City
Cluj Napoca
State/Province
Cluj
ZIP/Postal Code
400370
Country
Romania
Facility Name
Servicio de Pediatria
City
Linares
State/Province
Jaen
ZIP/Postal Code
23700
Country
Spain
Facility Name
University Hospital Germans Trias i Pujol
City
Badalona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Drottning Silvias Barnsjukhus
City
Gothenberg
ZIP/Postal Code
41685
Country
Sweden
Facility Name
Karolinska University Hospital
City
Stockholm
ZIP/Postal Code
14186
Country
Sweden
Facility Name
Royal Surrey County Hospital
City
Guildford
State/Province
Surrey
ZIP/Postal Code
GU2 5XX
Country
United Kingdom
Facility Name
Bath and NE Somerset Primary Care Trust
City
Bath
ZIP/Postal Code
BA1 3QE
Country
United Kingdom
Facility Name
Addenbrooke's Hospital
City
Cambridge
ZIP/Postal Code
CB2 2QQ
Country
United Kingdom
Facility Name
Derbyshire Children's Hospital
City
Derby
ZIP/Postal Code
DE22 3NE
Country
United Kingdom
Facility Name
Royal Hospital for Sick Children
City
Glasgow
ZIP/Postal Code
G3 8SJ
Country
United Kingdom
Facility Name
Great Ormond Street Hospital for Sick Children
City
London
ZIP/Postal Code
WC1N3JH
Country
United Kingdom
Facility Name
Royal Manchester Children's Hospital
City
Manchester
ZIP/Postal Code
M27 4HA
Country
United Kingdom
Facility Name
Royal Victoria Infirmary
City
Newcastle
ZIP/Postal Code
NE1 4LP
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
17185020
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. doi: 10.1016/j.ymgme.2006.09.001. Epub 2006 Dec 20.
Results Reference
background
PubMed Identifier
16912578
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. doi: 10.1097/01.gim.0000232477.37660.fb. 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].
Results Reference
background
PubMed Identifier
21150784
Citation
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. Erratum In: Genet Med. 2013 Oct;15(10):849.
Results Reference
result
PubMed Identifier
22929184
Citation
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.
Results Reference
derived

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

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