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NCT Number: NCT00630747

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

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.

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Key information

Conditions

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

Age range

5 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

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

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Idursulfase

Biological

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

Other names: Elaprase®, iduronate-2-sulfatase

Primary outcomes

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

    Time frame: Baseline and at Week 105

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

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

    Time frame: Baseline and at Week 105

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

Secondary outcomes

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

    Time frame: Baseline and 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).

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

    Time frame: Baseline and at Week 105

    Determined by Magnetic Resonance Imaging (MRI). The change was calculated as Week 105 minus baseline.

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

    Time frame: Baseline and at Week 105

    Determined by urine testing. The change was calculated as Week 105 minus baseline.

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

    Time frame: Baseline and at Week 105

    Determined by echocardiogram. LVMI indexed to body surface area (g/m^2). The change was calculated as Week 105 minus baseline.

Sponsors and collaborators

Lead sponsor

Shire

Industry

Registry information

Official study 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

Important dates

Study start
2004
Primary completion
2008
Study completion
2008
First posted
Mar 7, 2008
Registry last updated
Jun 10, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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