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| ID | Type | Description | Link |
|---|---|---|---|
| SSP-004184AQ | Other Identifier | Shire |
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This study was terminated due to treatment stop resulting in an inability to draw conclusions from the data. Evaluation of nonclinical rat findings is ongoing.
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This is an open-label study to assess the pharmacokinetics, safety, efficacy and tolerability of SSP-004184AQ. The study consists of two phases: the pharmacokinetic phase, using a single 16 mg/kg dose of SSP-004184AQ; and the chronic dosing phase, during which patients will receive an additional 48 weeks of SSP-004184AQ dosing. Two age groups will be studied: 6-<12, and 12-<18 years old. The study is designed to initially assess the pharmacokinetics and safety of SSP-004184AQ in older children (adolescents, 12-<18 years old) and then if deemed safe, in younger children (6-<12 years old).
Pharmacokinetic Phase: Patients will receive a single 16 mg/kg dose of SSP-004184AQ in capsule form.
Chronic Dosing Phase: Patients will receive SSP-004184AQ capsules daily for 48 weeks. Doses may range from 8-60 mg/kg/d.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SPD602 (26 mg/kg) | Experimental | Oral SSP-004184AQ taken once daily for 48 weeks |
|
| SPD602 (36 mg/kg) | Experimental | Oral SSP-004184AQ taken once daily for 48 weeks. Starting dose based on transfusion burden and iron overload status. Doses may range from 8-60mg/kg/day depending on clinical response. |
|
| SPD602 (16 mg/kg) | Experimental | A single dose given in the initial pharmacokinetic phase. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SPD602 | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of SPD602 After a Single Oral Dose | The pharmacokinetic (PK) parameters of SPD602 were measured in plasma of all patients following a single capsule dose of SPD602 at 16 mg/kg at start of treatment on Day 1 and at the clinic visit on Day 2. PK blood samples were collected as follows: Pre-dose on Day 1 (within 60 minutes prior to investigational product administration) and at 0.5, 1, 2, 3, 4, 8 hours (±3 minutes) and 24 hours (±30 minutes) post-dose. Plasma concentrations of SPD602 were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were determined from plasma concentration-time data for SPD602 (total) by non-compartmental analysis. | Day 1 and up to 24 hours post-dose |
| Time of Maximum Observed Plasma Concentration Sampled During a Dosing Interval (Tmax) of SPD602 After a Single Oral Dose | The pharmacokinetic (PK) parameters of SPD602 were measured in plasma of all patients following a single capsule dose of SPD602 at 16 mg/kg at start of treatment on Day 1 and at the clinic visit on Day 2. PK blood samples were collected as follows: Pre-dose on Day 1 (within 60 minutes prior to investigational product administration) and at 0.5, 1, 2, 3, 4, 8 hours (±3 minutes) and 24 hours (±30 minutes) post-dose. Plasma concentrations of SPD602 were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were determined from plasma concentration-time data for SPD602 (total) by non-compartmental analysis. | Day 1 and up to 24 hours post-dose |
| Area Under The Plasma Concentration-Time Curve (AUC) From The Time of Dosing to The Last Measurable Concentration (AUClast) of SPD602 After a Single Oral Dose | The pharmacokinetic (PK) parameters of SPD602 were measured in plasma of all patients following a single capsule dose of SPD602 at 16 mg/kg at start of treatment on Day 1 and at the clinic visit on Day 2. PK blood samples were collected as follows: Pre-dose on Day 1 (within 60 minutes prior to investigational product administration) and at 0.5, 1, 2, 3, 4, 8 hours (±3 minutes) and 24 hours (±30 minutes) post-dose. Plasma concentrations of SPD602 were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were determined from plasma concentration-time data for SPD602 (total) by non-compartmental analysis. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in LIC Assessed by R2* MRI | The efficacy of SPD602 was assessed by determining LIC. Abdominal MRI data were collected by using R2* standard procedures and used to determine LIC. A negative change from baseline indicates that LIC decreased. | Baseline, 24 weeks, and 48 weeks |
| Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by R2* MRI |
Not provided
Inclusion Criteria
Parents willing and able to sign the approved informed consent for their children and subjects between the ages of 6 and <18 years willing and able to provide their assent (based on institutional guidelines).
Able to swallow whole capsules.
Age >6 and <18 years.
Transfusion-dependent subjects who have transfusional iron overload requiring chronic treatment with deferoxamine, deferasirox, or deferiprone. A transfusion dependent subject is defined in this study as one with a minimum transfusion history totaling more than 20 units of packed red blood cells OR a calculated iron load based on transfusion history of 200mg/kg AND a transfusion requirement of 7 or more transfusions per year; or, in subjects with sickle cell anemia, be iron overloaded but can be receiving transfusion exchange therapy in lieu of transfusions.
In the opinion of the Investigator (and in consultation with the subject's parents), the subject is able to discontinue all existing iron chelation therapies for a minimum period of 1-5 days prior first dose of SSP-004184AQ, for the initial pharmacokinetic period of 8 days (if applicable), and for up to 49 weeks if continuing into the chronic dosing phase.
Subjects able to have an MRI must have:
Serum ferritin >500ng/mL at Screening.
Mean of the previous 3 pre-transfusion hemoglobin concentrations greater than or equal to 7.5g/dL.
If appropriate, depending on age, female subjects of child-bearing potential need to use a medically acceptable method for birth control from screening until 30 days after the last dose of the study drug. Females of child-bearing potential must have a negative serum beta-HCG pregnancy test at the Screening Visit and a negative urine pregnancy test at the Baseline Visit. Females of child-bearing potential must agree to abstain from sexual activity that could result in pregnancy or agree to use acceptable methods of contraception.
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital Boston | Boston | Massachusetts | 02115 | United States | ||
| Children's Hospital of Philadelphia |
The study consisted a pharmacokinetic (PK) phase and a chronic dosing (CD) phase. A sufficient number of participants were screened to enroll 16 participants into the PK phase (8 participants per age cohort). These participants could consent to participate in the CD phase. Additional participants also participated in the CD phase.
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| ID | Title | Description |
|---|---|---|
| FG000 | 6 to <12 Year Old | During the pharmacokinetic phase, participants aged 6 to less than 12 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Screening/Enrollment |
|
Not provided
Not provided
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| Day 1 and up to 24 hours post-dose |
| Terminal Half-life (t1/2) of SPD602 After a Single Oral Dose | The pharmacokinetic (PK) parameters of SPD602 were measured in plasma of all patients following a single capsule dose of SPD602 at 16 mg/kg at start of treatment on Day 1 and at the clinic visit on Day 2. PK blood samples were collected as follows: Pre-dose on Day 1 (within 60 minutes prior to investigational product administration) and at 0.5, 1, 2, 3, 4, 8 hours (±3 minutes) and 24 hours (±30 minutes) post-dose. Plasma concentrations of SPD602 were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were determined from plasma concentration-time data for SPD602 (total) by non-compartmental analysis. | Day 1 and up to 24 hours post-dose |
| Renal Clearance (CLr) of SPD602 After a Single Oral Dose | The pharmacokinetic (PK) parameters of SPD602 were measured in urine of patients following a single capsule dose of SPD602 at 16 mg/kg at start of treatment on Day 1 and at the clinic visit on Day 2. Children who could cooperate provided urine samples for PK assessment on Day 1 over 3 time intervals: 0-4, 4-8, and 8-24 hours after the last dose (continued into Day 2). Urine concentrations of SPD602 were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were determined from urine concentration-time data for SPD602 (total) by non-compartmental analysis. | Day 1 and up to 24 hours post-dose |
| Amount Excreted Into Urine (Ue) of SPD602 After a Single Oral Dose | The pharmacokinetic (PK) parameters of SPD602 were measured in urine of patients following a single capsule dose of SPD602 at 16 mg/kg at start of treatment on Day 1 and at the clinic visit on Day 2. Children who could cooperate provided urine samples for PK assessment on Day 1 over 3 time intervals: 0-4, 4-8, and 8-24 hours after the last dose (continued into Day 2). Urine concentrations of SPD602 were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were determined from urine concentration-time data for SPD602 (total) by non-compartmental analysis. | Day 1 and up to 24 hours post-dose |
| Fraction Of Orally Administered Drug Excreted Unchanged In Urine (fe) of SPD602 After a Single Oral Dose | The pharmacokinetic (PK) parameters of SPD602 were measured in urine of patients following a single capsule dose of SPD602 at 16 mg/kg at start of treatment on Day 1 and at the clinic visit on Day 2. Children who could cooperate provided urine samples for PK assessment on Day 1 over 3 time intervals: 0-4, 4-8, and 8-24 hours after the last dose (continued into Day 2). Urine concentrations of SPD602 were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were determined from urine concentration-time data for SPD602 (total) by non-compartmental analysis. | Day 1 and up to 24 hours post-dose |
| Change From Baseline in Liver Iron Concentration (LIC) Assessed by FerriScan R2 Magnetic Resonance Imaging (MRI) | The efficacy of SPD602 was assessed by determining LIC. Abdominal MRI data were collected by using FerriScan R2 standard procedures and used to determine LIC. A negative change from baseline indicates that LIC decreased. | Baseline, 24 weeks, and 48 weeks |
| Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by FerriScan R2 MRI | The efficacy of SPD602 was assessed by determining LIC and adjusting for transfusional iron intake. Abdominal MRI data were collected by using FerriScan R2 standard procedures and used to determine LIC. A negative change from baseline indicates that LIC decreased. | Baseline, 24 weeks, and 48 weeks |
The efficacy of SPD602 was assessed by determining LIC and adjusting for transfusional iron intake. Abdominal MRI data were collected by using R2* standard procedures and used to determine LIC. A negative change from baseline indicates that LIC decreased. |
| Baseline, 24 weeks, and 48 weeks |
| Change From Baseline in Cardiac Iron Load Assessed by T2* MRI | The efficacy of SPD602 was assessed by determining cardiac iron load. Cardiac MRI data were collected by using T2* standard procedures and used to determine iron load. A negative change from baseline indicates that iron load increased. | Baseline, 24 weeks, and 48 weeks |
| Change From Baseline in Serum Ferritin | Serum ferritin levels were assessed to determine if a participant was a successful responder and were determined from serum biochemistry analyses conducted at the central laboratories. A negative change from baseline indicates that serum ferritin decreased. | Baseline, 24 weeks, and 48 weeks |
| Philadelphia |
| Pennsylvania |
| 19104 |
| United States |
| Toronto Sick Kids Hospital | Toronto | Ontario | Canada |
| Ospedale Regionale Mecrocitemie | Cagliari | 09121 | Italy |
| Centro della Microcitemia e delle Anemie Congenite | Genoa | Italy |
| Thalassemia Center San Luigi Hospital | Orbassano | Italy |
| American University of Beirut Medical Center | Beirut | Lebanon |
| Chronic Care Center | Beirut | Lebanon |
| Ege University Hospital | Izmir | 35100 | Turkey (Türkiye) |
| FG001 | 12 to <18 Year Old | During the pharmacokinetic phase, participants aged 12 to less than 18 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response. |
| COMPLETED |
|
| NOT COMPLETED |
|
| Pharmacokinetic (PK) Phase |
|
| Chronic Dosing (CD) Phase |
|
|
The Safety Analysis Set, defined as all participants who had taken at least 1 dose of investigational product.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 6 to <12 Year Old | During the pharmacokinetic phase, participants aged 6 to less than 12 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response. |
| BG001 | 12 to <18 Year Old | During the pharmacokinetic phase, participants aged 12 to less than 18 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Observed Plasma Concentration (Cmax) of SPD602 After a Single Oral Dose | The pharmacokinetic (PK) parameters of SPD602 were measured in plasma of all patients following a single capsule dose of SPD602 at 16 mg/kg at start of treatment on Day 1 and at the clinic visit on Day 2. PK blood samples were collected as follows: Pre-dose on Day 1 (within 60 minutes prior to investigational product administration) and at 0.5, 1, 2, 3, 4, 8 hours (±3 minutes) and 24 hours (±30 minutes) post-dose. Plasma concentrations of SPD602 were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were determined from plasma concentration-time data for SPD602 (total) by non-compartmental analysis. | The Pharmacokinetic (PK) set, defined as all participants in the Safety Analysis Set for whom the primary PK data were considered sufficient and interpretable. The Safety Analysis Set was defined as all participants who had taken at least 1 dose of investigational product. Treatment assignment was based on the treatment actually received. | Posted | Mean | Standard Deviation | ng/mL | Day 1 and up to 24 hours post-dose |
|
|
| ||||||||||||||||||||||||||||
| Primary | Time of Maximum Observed Plasma Concentration Sampled During a Dosing Interval (Tmax) of SPD602 After a Single Oral Dose | The pharmacokinetic (PK) parameters of SPD602 were measured in plasma of all patients following a single capsule dose of SPD602 at 16 mg/kg at start of treatment on Day 1 and at the clinic visit on Day 2. PK blood samples were collected as follows: Pre-dose on Day 1 (within 60 minutes prior to investigational product administration) and at 0.5, 1, 2, 3, 4, 8 hours (±3 minutes) and 24 hours (±30 minutes) post-dose. Plasma concentrations of SPD602 were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were determined from plasma concentration-time data for SPD602 (total) by non-compartmental analysis. | The PK set, defined as all participants in the Safety Analysis Set for whom the primary PK data were considered sufficient and interpretable. | Posted | Median | Full Range | hours | Day 1 and up to 24 hours post-dose |
| ||||||||||||||||||||||||||||||
| Primary | Area Under The Plasma Concentration-Time Curve (AUC) From The Time of Dosing to The Last Measurable Concentration (AUClast) of SPD602 After a Single Oral Dose | The pharmacokinetic (PK) parameters of SPD602 were measured in plasma of all patients following a single capsule dose of SPD602 at 16 mg/kg at start of treatment on Day 1 and at the clinic visit on Day 2. PK blood samples were collected as follows: Pre-dose on Day 1 (within 60 minutes prior to investigational product administration) and at 0.5, 1, 2, 3, 4, 8 hours (±3 minutes) and 24 hours (±30 minutes) post-dose. Plasma concentrations of SPD602 were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were determined from plasma concentration-time data for SPD602 (total) by non-compartmental analysis. | The PK set, defined as all participants in the Safety Analysis Set for whom the primary PK data were considered sufficient and interpretable. | Posted | Mean | Standard Deviation | h*mg/L | Day 1 and up to 24 hours post-dose |
| ||||||||||||||||||||||||||||||
| Primary | Terminal Half-life (t1/2) of SPD602 After a Single Oral Dose | The pharmacokinetic (PK) parameters of SPD602 were measured in plasma of all patients following a single capsule dose of SPD602 at 16 mg/kg at start of treatment on Day 1 and at the clinic visit on Day 2. PK blood samples were collected as follows: Pre-dose on Day 1 (within 60 minutes prior to investigational product administration) and at 0.5, 1, 2, 3, 4, 8 hours (±3 minutes) and 24 hours (±30 minutes) post-dose. Plasma concentrations of SPD602 were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were determined from plasma concentration-time data for SPD602 (total) by non-compartmental analysis. | The PK set, defined as all participants in the Safety Analysis Set for whom the primary PK data were considered sufficient and interpretable. | Posted | Mean | Standard Deviation | hours | Day 1 and up to 24 hours post-dose |
| ||||||||||||||||||||||||||||||
| Primary | Renal Clearance (CLr) of SPD602 After a Single Oral Dose | The pharmacokinetic (PK) parameters of SPD602 were measured in urine of patients following a single capsule dose of SPD602 at 16 mg/kg at start of treatment on Day 1 and at the clinic visit on Day 2. Children who could cooperate provided urine samples for PK assessment on Day 1 over 3 time intervals: 0-4, 4-8, and 8-24 hours after the last dose (continued into Day 2). Urine concentrations of SPD602 were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were determined from urine concentration-time data for SPD602 (total) by non-compartmental analysis. | The PK set, defined as all participants in the Safety Analysis Set for whom the primary PK data were considered sufficient and interpretable. | Posted | Mean | Standard Deviation | L/h | Day 1 and up to 24 hours post-dose |
| ||||||||||||||||||||||||||||||
| Primary | Amount Excreted Into Urine (Ue) of SPD602 After a Single Oral Dose | The pharmacokinetic (PK) parameters of SPD602 were measured in urine of patients following a single capsule dose of SPD602 at 16 mg/kg at start of treatment on Day 1 and at the clinic visit on Day 2. Children who could cooperate provided urine samples for PK assessment on Day 1 over 3 time intervals: 0-4, 4-8, and 8-24 hours after the last dose (continued into Day 2). Urine concentrations of SPD602 were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were determined from urine concentration-time data for SPD602 (total) by non-compartmental analysis. | The PK set, defined as all participants in the Safety Analysis Set for whom the primary PK data were considered sufficient and interpretable. | Posted | Mean | Standard Deviation | mg | Day 1 and up to 24 hours post-dose |
| ||||||||||||||||||||||||||||||
| Primary | Fraction Of Orally Administered Drug Excreted Unchanged In Urine (fe) of SPD602 After a Single Oral Dose | The pharmacokinetic (PK) parameters of SPD602 were measured in urine of patients following a single capsule dose of SPD602 at 16 mg/kg at start of treatment on Day 1 and at the clinic visit on Day 2. Children who could cooperate provided urine samples for PK assessment on Day 1 over 3 time intervals: 0-4, 4-8, and 8-24 hours after the last dose (continued into Day 2). Urine concentrations of SPD602 were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were determined from urine concentration-time data for SPD602 (total) by non-compartmental analysis. | The PK set, defined as all participants in the Safety Analysis Set for whom the primary PK data were considered sufficient and interpretable. | Posted | Mean | Standard Deviation | percentage of total dose | Day 1 and up to 24 hours post-dose |
| ||||||||||||||||||||||||||||||
| Primary | Change From Baseline in Liver Iron Concentration (LIC) Assessed by FerriScan R2 Magnetic Resonance Imaging (MRI) | The efficacy of SPD602 was assessed by determining LIC. Abdominal MRI data were collected by using FerriScan R2 standard procedures and used to determine LIC. A negative change from baseline indicates that LIC decreased. | The Full Analysis Set (FAS), defined as all participants in the Safety Analysis Set who had at least 1 post-baseline primary efficacy assessment, which was considered as the LICs assessed from FerriScan R2 MRI. | Posted | Mean | Standard Deviation | mg Fe/g*dw | Baseline, 24 weeks, and 48 weeks |
| ||||||||||||||||||||||||||||||
| Primary | Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by FerriScan R2 MRI | The efficacy of SPD602 was assessed by determining LIC and adjusting for transfusional iron intake. Abdominal MRI data were collected by using FerriScan R2 standard procedures and used to determine LIC. A negative change from baseline indicates that LIC decreased. | The FAS, defined as all participants in the Safety Analysis Set who had at least 1 post-baseline primary efficacy assessment, which was considered as the LICs assessed from FerriScan R2 MRI. | Posted | Mean | Standard Deviation | mg Fe/g*dw | Baseline, 24 weeks, and 48 weeks |
| ||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in LIC Assessed by R2* MRI | The efficacy of SPD602 was assessed by determining LIC. Abdominal MRI data were collected by using R2* standard procedures and used to determine LIC. A negative change from baseline indicates that LIC decreased. | The FAS, defined as all participants in the Safety Analysis Set who had at least 1 post-baseline primary efficacy assessment, which was considered as the LICs assessed from FerriScan R2 MRI. | Posted | Mean | Standard Deviation | mg Fe/g*dw | Baseline, 24 weeks, and 48 weeks |
| ||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by R2* MRI | The efficacy of SPD602 was assessed by determining LIC and adjusting for transfusional iron intake. Abdominal MRI data were collected by using R2* standard procedures and used to determine LIC. A negative change from baseline indicates that LIC decreased. | The FAS, defined as all participants in the Safety Analysis Set who had at least 1 post-baseline primary efficacy assessment, which was considered as the LICs assessed from FerriScan R2 MRI. | Posted | Mean | Standard Deviation | mg Fe/g*dw | Baseline, 24 weeks, and 48 weeks |
| ||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Cardiac Iron Load Assessed by T2* MRI | The efficacy of SPD602 was assessed by determining cardiac iron load. Cardiac MRI data were collected by using T2* standard procedures and used to determine iron load. A negative change from baseline indicates that iron load increased. | The FAS, defined as all participants in the Safety Analysis Set who had at least 1 post-baseline primary efficacy assessment, which was considered as the LICs assessed from FerriScan R2 MRI. | Posted | Mean | Standard Deviation | milliseconds | Baseline, 24 weeks, and 48 weeks |
| ||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Serum Ferritin | Serum ferritin levels were assessed to determine if a participant was a successful responder and were determined from serum biochemistry analyses conducted at the central laboratories. A negative change from baseline indicates that serum ferritin decreased. | The FAS, defined as all participants in the Safety Analysis Set who had at least 1 post-baseline primary efficacy assessment, which was considered as the LICs assessed from FerriScan R2 MRI. | Posted | Mean | Standard Deviation | ng/mL | Baseline, 24 weeks, and 48 weeks |
|
Not provided
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Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 6 to <12 Year Old | During the pharmacokinetic phase, participants aged 6 to less than 12 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response. | 0 | 13 | 13 | 13 | ||
| EG001 | 12 to <18 Year Old | During the pharmacokinetic phase, participants aged 12 to less than 18 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response. | 0 | 16 | 15 | 16 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Hearing impaired | Ear and labyrinth disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Tinnitus | Ear and labyrinth disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Chest discomfort | General disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
| |
| Hordeolum | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
| |
| Molluscum contagiosum | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
| |
| Otitis externa | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
| |
| Pharyngitis streptococcal | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
| |
| Tonsillitis | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (12.1) | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (12.1) | Systematic Assessment |
| |
| Foot fracture | Injury, poisoning and procedural complications | MedDRA (12.1) | Systematic Assessment |
| |
| Head injury | Injury, poisoning and procedural complications | MedDRA (12.1) | Systematic Assessment |
| |
| Joint injury | Injury, poisoning and procedural complications | MedDRA (12.1) | Systematic Assessment |
| |
| Joint sprain | Injury, poisoning and procedural complications | MedDRA (12.1) | Systematic Assessment |
| |
| Limb injury | Injury, poisoning and procedural complications | MedDRA (12.1) | Systematic Assessment |
| |
| Skin laceration | Injury, poisoning and procedural complications | MedDRA (12.1) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (12.1) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (12.1) | Systematic Assessment |
| |
| Glucose tolerance test abnormal | Investigations | MedDRA (12.1) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (12.1) | Systematic Assessment |
| |
| Spleen palpable | Investigations | MedDRA (12.1) | Systematic Assessment |
| |
| Transaminases increased | Investigations | MedDRA (12.1) | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA (12.1) | Systematic Assessment |
| |
| Folate deficiency | Metabolism and nutrition disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Osteochondrosis | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Sensation of heaviness | Musculoskeletal and connective tissue disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Head discomfort | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Hyporeflexia | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Muscle contractions involuntary | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Sinus headache | Nervous system disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Chromaturia | Renal and urinary disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Amenorrhoea | Reproductive system and breast disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Pharyngeal erythema | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Pharyngeal haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Upper airway obstruction | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Blister | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Skin haemorrhage | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA (12.1) | Systematic Assessment |
| |
| Hyperaemia | Vascular disorders | MedDRA (12.1) | Systematic Assessment |
|
This study was terminated early because of non-clinical safety results. As such, not all subjects completed the study. The available efficacy data were summarized and analyzed as specified in the SAP; however, no efficacy conclusions could be drawn.
If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Shire | +1 866 842 5335 | ClinicalTransparency@shire.com |
| ID | Term |
|---|---|
| D017086 | beta-Thalassemia |
| D000755 | Anemia, Sickle Cell |
| D019190 | Iron Overload |
| ID | Term |
|---|---|
| D013789 | Thalassemia |
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D019189 | Iron Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| Physician Decision |
|
| Early study termination |
|
| Male |
|
|
|
During the pharmacokinetic phase, participants aged 12 to less than 18 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
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