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

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

Status

Completed

Phases

Phase 2Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00630747

Enrollment

Registered

2008-03-07

Start date

2004-09-13

Completion date

2008-01-31

Last updated

2021-06-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

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.

Interventions

BIOLOGICALIdursulfase

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

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

5 Years to No maximum

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.

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Mean Percent Predicted Forced Vital Capacity (FVC) at Week 105	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	Baseline and at Week 105	Determined on a walking course. The change was calculated as Week 105 minus baseline.

Secondary

Measure	Time frame	Description
Change From Baseline in Mean Passive Joint Range of Motion (JROM) at Week 105	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	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	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	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.

Countries

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

Participant flow

Recruitment details

This study allows participants in double-blind phase of Study TKT024 (NCT00069641), a 1 year Phase 2/3 registration study, to continue long-term idursulfase therapy and to allow placebo participants in TKT024 to receive active idursulfase treatment. The first participant enrolled on 13 Sep 2004. The study was conducted at 52 sites in 17 countries.

Pre-assignment details

Participants were screened for entry based on their known medical histories and previous participation in the TKT024 study. Participants had to have completed Week 53 final evaluations in the TKT024 study. Participants were not to have received any treatment with an investigational therapy other than idursulfase within 60 days of study entry.

Participants by arm

Arm	Count
Idursulfase (0.5 mg/kg, IV, Once-weekly) Idursulfase 0.5 mg/kg administered by IV infusion once-weekly.	94
Total	94

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Death	1
Overall Study	Returned to country of origin	1
Overall Study	Transferred to Study TKT031NPU	7

Baseline characteristics

Characteristic	Idursulfase (0.5 mg/kg, IV, Once-weekly)
Age, Categorical <=18 years	70 Participants
Age, Categorical >=65 years	0 Participants
Age, Categorical Between 18 and 65 years	24 Participants
Age, Continuous	14.52 years STANDARD_DEVIATION 6.634
Baseline Cardiac Left Ventricular Mass Index (LVMI)	97.64 gram per meter^2 (g/m^2) STANDARD_DEVIATION 36.606
Baseline Combined Liver and Spleen Volume	1504.8 cubic centimeters (cc) STANDARD_DEVIATION 417.21
Baseline Distance Walked in the 6-minute Walk Test (6MWT)	400.3 meters (m) STANDARD_DEVIATION 100.25
Baseline Normalized Urine Glycosaminoglycans (GAG) Levels	361.96 microgram(mcg)GAG/mg creatinine STANDARD_DEVIATION 136.132
Baseline Passive Joint Range of Motion (JROM)	67.44 percentage of JROM STANDARD_DEVIATION 9.042
Baseline Percent Predicted Forced Vital Capacity (FVC)	56.160 percent predicted FVC STANDARD_DEVIATION 14.897
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	79 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants
Race (NIH/OMB) Asian	5 Participants
Race (NIH/OMB) Black or African American	6 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants
Race (NIH/OMB) White	78 Participants
Region of Enrollment Europe	40 Participants
Region of Enrollment North America	34 Participants
Region of Enrollment South America	20 Participants
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	94 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	94 / 94
serious Total, serious adverse events	38 / 94