Trial Information

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 TKT024EXT was conducted in 2 phases. The first phase consisted of a 2-year period with
each year consisting of 52 weekly infusions of idursulfase. 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). Certain final evaluations from Study TKT024 served as the baseline assessments
for this study. Safety and efficacy outcomes 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 and clinical outcomes were identical to those evaluated in the
double-blind phase of Study TKT024. Forced vital capacity (FVC) and the 6-minute walk test
(6MWT) continued to be the primary clinical outcomes of this study. Data were also
collected on significant clinical events that reflect disease progression in this patient
population. The focus was on events involving the major organ systems affected by MPS II:
cardiac, respiratory, skeletal, and neurological.

The second phase of the study consisted of weekly infusions of IV idursulfase 0.5 mg/kg and
monitoring patients for safety (via collection of adverse events, concomitant medications,
and vital signs). Patients continued treatment during the second study phase until they
transitioned to commercially available idursulfase or they discontinued this study for other
reasons. Study completion was defined as the time a patient either transitioned to
commercially available idursulfase or discontinued this study for other reasons.

Week 105 defined the beginning of the second study phase. Patients had a scheduled
evaluation every 6 months until they completed or discontinued the study, including a safety
evaluation (assessment of adverse events, concomitant medications, physical examination,
clinical laboratory values, and anti-idursulfase antibodies), measurement of urine GAG
levels, and collection of long-term clinical events. At the time a patient completed or
discontinued the study, the patient should have had an "End of Study" evaluation consisting
of assessment of adverse events, concomitant medications, 12-lead electrocardiogram (ECG),
physical examination (including measurement of height, weight, and head circumference),
clinical laboratory evaluations (including measurement of anti-idursulfase antibodies),
measurement of urine GAG levels, and collection of long-term clinical events. In addition,
patients who discontinued this study for reasons other than transitioning to commercially
available idursulfase had an additional safety assessment 30 days after their last infusion.

To fulfill the secondary objective of this study, a commercial-scale manufacturing lot of
idursulfase was introduced into the trial as soon as it was available, in order to begin
generating safety data on this drug product. Pharmacokinetic (PK) data on this
commercial-scale material was also obtained from the PK studies conducted during the first
year of the study.

Initially, patients continued to receive their weekly infusions at the same study centers as
in Study TKT024. However, based on an acceptable safety experience, patients were
transitioned to investigational centers closer to their homes to receive their infusions.
During the first phase of this study, patients were required to return to the main testing
sites every 4 months during the first year and every 6 months during the second year for
their major study evaluations. During the second phase, patients received their infusions
and had all scheduled evaluations at the local clinical sites.