Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as HGT-2310
Idursulfase-IT · 5 trials · 1 indication
An adverse event (AE) means any untoward medical occurrence in a participant or participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. The severity of AEs will be determined per the investigator's assessment.
An AE means any untoward medical occurrence in a participant or participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. Any adverse event related to idursulfase-IT will be reported in this outcome measure.
An AE means any untoward medical occurrence in a participant or participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. Any adverse event related to the IDDD will be reported in this outcome measure.
An AE means any untoward medical occurrence in a participant or participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. Any adverse event related to device surgical procedure will be reported in this outcome measure.
An AE means any untoward medical occurrence in a participant or participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. Any adverse event related to IT administration process will be reported in this outcome measure.
An AE means any untoward medical occurrence in a participant or participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. Any adverse event related to IV elaprase infusion will be reported in this outcome measure.
An AE is any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered investigational product-related.
Participants were assessed for clinically significant changes in vital signs like injection (IT) vital signs and regular vital signs (temperature, pulse, blood pressure \[systolic and diastolic\], oxygen saturation, and respiration rate).
Participants were assessed for clinically significant changes in laboratory parameters such as chemistry, hematology, urinalysis and cerebrospinal fluid (CSF) values.
Participants were assessed for clinically significant changes in 12-lead ECG findings (such as heart rate, PR interval, QRS interval, QT interval, and the corrected QT interval).
Idursulfase concentrations in serum were determined using a validated Enzyme -Linked Immunosorbent Assay (ELISA) method. Concentration for Cmax is presented in this endpoint.
The percent change in concentration of GAG in CSF was assessed. GAGs are long sugar chains that are like building blocks for the body's tissues, especially connective tissues like cartilage, skin, and tendons, and play a crucial role in cell signaling and interactions.
The percent change in concentration of GAG in urine was assessed. GAGs are long sugar chains that are like building blocks for the body's tissues, especially connective tissues like cartilage, skin, and tendons, and play a crucial role in cell signaling and interactions.
The DAS-II was used to assess cognitive development in all randomized participants. The GCA standard score of the DAS-II was used to obtain a general measure of cognitive ability. The GCA score represent a score (mean = 100 and standard deviation of 15) on which higher scores indicate a higher level of cognitive ability. The score ranges from 30 to 170. A positive change value indicates improvement in cognitive ability.
An adverse event (AE) is any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, and/or laboratory changes occurring in any phase of a clinical trial, and whether or not considered study drug-related. TEAEs were defined as all AEs occurring on or after the first IDDD surgery date or first dose (whichever is earlier) for the participant (whether it is in this extension study or in HGT HIT-045 \[NCT00920647\]) and before the end of the study (EOS) visit (+30 days). For Idursulfase-IT 1 mg+10 mg arm the summary presented includes only the TEAEs that occurred while the participants were assigned to 10 mg.
Number of participants with clinically significant changes in laboratory parameters (chemistry, hematology, urinalysis and CSF values) were collected.
Number of participants with clinically significant changes in 12-lead Electrocardiogram (ECG) findings (heart rate, PR interval, QRS interval, QT interval and the corrected QT interval) were collected.
ITT patient population
White blood cell count in CSF was monitored throughout the study as a way of assessing any potential inflammation of the meninges induced by idursulfase-IT.
Reflects development of anti-idursulfase antibodies post baseline.
Electrocardiogram (ECG) parameters included: heart rate, sinus rhythm, atrial/ventricular hypertrophy, PR, QRS, QT and QTc intervals.
| Arm | Type | Description |
|---|---|---|
| Idursulfase-IT | EXPERIMENTAL | Participants will receive idursulfase-IT once monthly and weekly IV infusions of elaprase at the dose used in previous studies (HGT-HIT-045/SHP609-302) via IDDD until benefit is no longer derived from the treatment, or treatment is no longer tolerable, or up to approximately 4.8 years. |
| Nontreatment control | OTHER | Patients will receive weekly standard of care treatment with IV Elaprase only. |
| Idursulfase-IT 1 milligram (mg) | EXPERIMENTAL | Participants will receive 1 mg idursulfase-IT intrathecally via intrathecal drug delivery device (IDDD) or lumbar puncture (LP) once monthly and standard-of-care (SoC) therapy of Elaprase intravenous (IV) infusions. |
| Idursulfase-IT 10 mg | EXPERIMENTAL | Participants will receive 10 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions. |
| Idursulfase-IT 30 mg | EXPERIMENTAL | Participants will receive 30 mg idursulfase-IT intrathecally via IDDD or LP once monthly and SoC therapy of Elaprase IV infusions. |
| Control | OTHER | Untreated Patients |
| Idursulfase -IT (1 mg) | EXPERIMENTAL | monthly using an intrathecal drug delivery device (IDDD) |
| Idursulfase-IT (10 mg) | EXPERIMENTAL | monthly using an intrathecal drug delivery device (IDDD) |
| Idursulfase -IT (30 mg) | EXPERIMENTAL | monthly using an intrathecal drug delivery device (IDDD) |
| Name | Type | Description |
|---|---|---|
| Idursulfase-IT | DRUG | Idursulfase-IT intrathecally via IDDD. |
| Elaprase | DRUG | Elaprase IV infusion. |
| No IT treatment | OTHER | Standard of Care |
| Control | OTHER | 3 dose cohorts were planned. Within each dose cohort, patients will be randomized to 1 of 2 treatment options: treatment with study drug or no treatment with 4 treated patients per dose group and a total of 4 untreated patients (1-2 untreated patients will be assigned in each dose cohort). They will not undergo surgical placement of an Intrathecal Drug Delivery Device (IDDD), and will not receive Idursulfase-IT. |
| Idursulfase IT (1 mg) | DRUG | The original design of the study was to test the dose levels of 10, 30 and 100 mg. This was based on a calculation of a minimally effective dose around 10 mg, with subsequent dose levels being chosen as increasing half-log steps. During the conduct of the study; however, it became clear that the 10 mg dose elicited a strong Pharmacodynamic response, as measured by a dramatic and sustained drop in the CSF GAG levels. This indicated the need to explore a lower level as a minimally effective dose level, leading to the introduction of the 1 mg group. Enrollment of patients in this dose cohort will commence after the last patient has been enrolled in 30 mg dose cohort. 4 patients will be undergo surgical placement of an IDDD and receive 1 mg idursulfase-IT as an IT injection via an IDDD once per month (ie, every 28 days) for 6 month. |
| Idursulfase IT (10 mg) | DRUG | Patients will be enrolled in 10 mg dose cohort and 30 mg dose cohort in a sequential, escalating fashion. 4 patients will undergo surgical placement of an IDDD and receive 10 mg idursulfase-IT as an intrathecal (IT) injection via an IDDD once per month (ie, every 28 days) for 6 month. |
| Idursulfase IT (30 mg) | DRUG | Patients will be enrolled in 10 mg dose cohort and 30 mg dose cohort in a sequential, escalating fashion. 4 patients will undergo surgical placement of an IDDD and receive 30 mg idursulfase-IT as an IT injection via an IDDD once per month (ie, every 28 days) for 6 month. |
Inclusion Criteria: 1. The participant must have completed end of study assessments in studies HGT-HIT-046 \[NCT01506141\] or SHP609-302 \[NCT02412787\] and received a clinical benefit from idursulfase-IT in the opinion of the investigator. 2. The participant, or participant's legally designated re...
Idursulfase-IT is an investigational therapy being studied for Hunter syndrome, also called mucopolysaccharidosis II, in patients who have cognitive impairment. It is administered intrathecally, meaning directly into the cerebrospinal fluid, and is given in conjunction with Elaprase, an intravenous enzyme replacement therapy. It remains in clinical development and is not approved.
Idursulfase-IT is being developed by Takeda Pharmaceutical Company Limited, which trades under the ticker TAK. Takeda has sponsored the clinical program evaluating the therapy in pediatric and adult patients with Hunter syndrome and cognitive impairment, including studies combining intrathecal idursulfase-IT with intravenous Elaprase.
Idursulfase-IT is in Phase 2 clinical development. It is an investigational therapy and has not been approved by the FDA. The program includes completed Phase 1 and Phase 2 studies as well as an ongoing Phase 2 extension study in children and adults with Hunter syndrome and cognitive impairment.
Idursulfase-IT has been evaluated in five clinical trials. The active study is NCT06031259, a Phase 2 extension trial in Canada and France. Completed trials include NCT02412787, NCT02055118, and NCT01506141, which tested intrathecal idursulfase-IT with Elaprase in pediatric patients with Hunter syndrome and cognitive impairment.
Yes. Idursulfase-IT is also known as Idursulfase IT and Idursulfase IT (1 mg). These names refer to the same investigational intrathecal formulation developed by Takeda for Hunter syndrome. The 1 mg designation reflects the dose strength used in the clinical program.
Across the five clinical trials of Idursulfase-IT, total enrollment is 151 participants. The studies enrolled male patients with Hunter syndrome, with some trials including pediatric participants as young as 3 years old. The largest completed study, NCT02055118, enrolled 58 patients across the United States, Australia, Canada, France, Mexico, Spain, and the United Kingdom.