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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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 Summary:

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.

Current Primary Outcome:

• 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.
• 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.

Original Primary Outcome:

• Measurements of the six-minute-walk test (6-MWT) and forced vital capacity (FVC) [ Time Frame: 2 years ]
• Collection of adverse events (including infusion-related adverse events), and changes in 12-lead ECG, vital signs, physical exams, standard laboratory parameters, and anti-idursulfase antibody status. [ Time Frame: 2+ years ]

Current Secondary Outcome:

• 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).
• 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.
• 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.
• 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.

Original Secondary Outcome:

• Measurements of joint range of motion (JROM) [ Time Frame: 2 years ]
• Measurements of combined liver and spleen size [ Time Frame: 2 years ]
• Measurements of urine GAG levels [ Time Frame: 2+ years ]
• Measurements of cardiac left ventricular mass (LVM) [ Time Frame: 2 years ]

Dates:
Date Received: February 28, 2008
Date Started: September 2004
Date Completion:
Last Updated: July 16, 2015
Last Verified: May 2014