A Phase 2/3 interventional study of Idursulfase in Hunter Syndrome and Mucopolysaccharidosis II (MPS II), sponsored by Shire. Completed at 52 sites in 10 countries. Open to male participants aged 5 Years and older. Per ClinicalTrials.gov, last updated 2021-06-10.
Sponsored by Shire · Phase 2/3, Interventional, and Treatment
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.
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.
71 studies on the registry are indexed under Mucopolysaccharidosis II; 8 are open to participants now.
This study's enrollment of 94 is above the median of 20 across 43 interventional studies indexed under Mucopolysaccharidosis II.
Browse Mucopolysaccharidosis II studies →Shire is the lead sponsor of 346 studies on the registry; 2 are open to participants now.
Of its 47 completed or terminated interventional studies of FDA-regulated products, 47 (100%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Biological: Idursulfase
Solution for intravenous infusion, 0.5 mg/kg once-weekly
Also known as: Elaprase®, iduronate-2-sulfatase
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.
Time frame: Baseline and at Week 105
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.
Time frame: Baseline and at Week 105
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).
Time frame: Baseline and at Week 105
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.
Time frame: Baseline and at Week 105
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.
Time frame: Baseline and at Week 105
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.
Time frame: Baseline and at Week 105
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.
| Milestone | Idursulfase (0.5 mg/kg, IV, Once-weekly) |
|---|---|
| Started | 94 |
| Participants treated in phase i of study | 94 |
| Completed | 85 |
| Not completed | 9 |
| Withdrew: Death | 1 |
| Withdrew: Transferred to study tkt031npu | 7 |
| Withdrew: Returned to country of origin | 1 |
Determined by spirometry. The change is calculated as Week 105 minus baseline.
| percent predicted FVC | Idursulfase (0.5 mg/kg, IV, Once-weekly) |
|---|---|
| Change From Baseline in Mean Percent Predicted Forced Vital Capacity (FVC) at Week 105 | -0.056 ± 1.059 |
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).
| percentage of JROM | Idursulfase (0.5 mg/kg, IV, Once-weekly) |
|---|---|
| Change From Baseline in Mean Passive Joint Range of Motion (JROM) at Week 105 | 0.63 ± 0.640 |
Determined by Magnetic Resonance Imaging (MRI). The change was calculated as Week 105 minus baseline.
| cubic centimeters (cc) | Idursulfase (0.5 mg/kg, IV, Once-weekly) |
|---|---|
| Change From Baseline in Mean Combined Liver and Spleen Volume at Week 105 | -325.5 ± 36.84 |
Determined by urine testing. The change was calculated as Week 105 minus baseline.
| mcg GAG/mg creatinine | Idursulfase (0.5 mg/kg, IV, Once-weekly) |
|---|---|
| Change From Baseline in Mean Normalized Urine Glycosaminoglycans (GAG) Levels at Week 105 | -238.25 ± 13.333 |
Determined by echocardiogram. LVMI indexed to body surface area (g/m\^2). The change was calculated as Week 105 minus baseline.
| g/m^2 | Idursulfase (0.5 mg/kg, IV, Once-weekly) |
|---|---|
| Change From Baseline in Mean Cardiac Left Ventricular Mass Index (LVMI) at Week 105 | 3.28 ± 3.826 |
Determined on a walking course. The change was calculated as Week 105 minus baseline.
| meters (m) | Idursulfase (0.5 mg/kg, IV, Once-weekly) |
|---|---|
| Change From Baseline in Mean Distance Walked in the 6-minute Walk Test (6MWT) at Week 105 | 23.0 ± 7.94 |
Collected over Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Idursulfase (0.5 mg/kg, IV, Once-weekly) | — | 38/94 (40.4%) | 94/94 (100%) |
| Event | Idursulfase (0.5 mg/kg, IV, Once-weekly) |
|---|---|
| Poor Venous AccessVascular disorders | 10/94 |
| Carpal Tunnel SyndromeNervous system disorders | 7/94 |
| BacteraemiaInfections and infestations | 3/94 |
| Pneumonia NOSInfections and infestations | 3/94 |
| Spinal Cord Compression NOSNervous system disorders | 3/94 |
| Umbilical Hernia NOSGastrointestinal disorders | 3/94 |
| Abdominal Pain NOSGastrointestinal disorders | 2/94 |
| Abdominal Strangulated HerniaGastrointestinal disorders | 2/94 |
| AppendicitisGastrointestinal disorders | 2/94 |
| Joint ContractureMusculoskeletal and connective tissue disorders | 2/94 |
| Event | Idursulfase (0.5 mg/kg, IV, Once-weekly) |
|---|---|
| PyrexiaGeneral disorders | 57/94 |
| CoughRespiratory, thoracic and mediastinal disorders | 53/94 |
| HeadacheBlood and lymphatic system disorders | 53/94 |
| Upper respiratory tract infection nosInfections and infestations | 47/94 |
| PharyngitisRespiratory, thoracic and mediastinal disorders | 46/94 |
| NasopharyngitisRespiratory, thoracic and mediastinal disorders | 39/94 |
| Vomiting nosGastrointestinal disorders | 39/94 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 39/94 |
| Nasal congestionRespiratory, thoracic and mediastinal disorders | 38/94 |
| Ear infection nosInfections and infestations | 36/94 |
| Age, Categorical(Participants) | Idursulfase (0.5 mg/kg, IV, Once-weekly) |
|---|---|
| <=18 years | 70 |
| Between 18 and 65 years | 24 |
| >=65 years | 0 |
| Age, Continuous(years) | Idursulfase (0.5 mg/kg, IV, Once-weekly) |
|---|---|
| Mean | 14.52 ± 6.634 |
| Sex: Female, Male(Participants) | Idursulfase (0.5 mg/kg, IV, Once-weekly) |
|---|---|
| Female | 0 |
| Male | 94 |
| Ethnicity (NIH/OMB)(Participants) | Idursulfase (0.5 mg/kg, IV, Once-weekly) |
|---|---|
| Hispanic or Latino | 15 |
| Not Hispanic or Latino | 79 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Idursulfase (0.5 mg/kg, IV, Once-weekly) |
|---|---|
| American Indian or Alaska Native | 3 |
| Asian | 5 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 6 |
| White | 78 |
| More than one race | 0 |
| Unknown or Not Reported | 2 |
| Region of Enrollment(Participants) | Idursulfase (0.5 mg/kg, IV, Once-weekly) |
|---|---|
| Europe | 40 |
| North America | 34 |
| South America | 20 |
| Baseline Percent Predicted Forced Vital Capacity (FVC)(percent predicted FVC) | Idursulfase (0.5 mg/kg, IV, Once-weekly) |
|---|---|
| Mean | 56.160 ± 14.897 |
| Baseline Distance Walked in the 6-minute Walk Test (6MWT)(meters (m)) | Idursulfase (0.5 mg/kg, IV, Once-weekly) |
|---|---|
| Mean | 400.3 ± 100.25 |
4 further baseline measures are reported on the registry.
This study is completed, as verified in May 2021. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Shire