Iron Overload Due to Repeated Red Blood Cell Transfusions
Conditions
Brief summary
The purpose of this study is to evaluate SSP-004184AQ in patients with transfusional iron overload whose primary diagnosis is hereditary or congenital anemia. SSP-004184AQ is an iron chelator under development for chronic daily oral administration to patients with transfusional iron overload.
Interventions
DRUGSPD602
50 mg/kg/day orally twice daily for 24 weeks
Sponsors
Shire
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Willing and able to sign the approved informed consent. * Age: 18-60 years old, inclusive, at Screening. * Subjects who have received more than 20 transfusions in their lifetime and who have transfusional iron overload requiring chronic treatment with an iron chelator. N.B.: Sickle Cell Disease subjects receiving regular exchange transfusions and iron overloaded subjects with thalassemia intermedia who are receiving regular transfusions (transfusion dependent thalassemia intermedia) are eligible. * Willing to discontinue all existing iron chelation therapies for a minimum period of one to five days prior to first dose of SSP-004184AQ, the 24 week duration of the study and 1 week after last dose for a total of approximately 26 weeks. * Willing to fast two hours prior to and one hour after each dose. * Serum ferritin \>500ng/mL at Screening. * Baseline liver iron concentration is greater than or equal to 5mg iron per g (equivalent dry weight, liver)determined by FerriScan® R2 MRI. * Mean of the previous three pre-transfusion hemoglobin concentrations is greater than or equal to 7.5g/dL. * Adult female subjects should be: 1. Post-menopausal (12 consecutive months of spontaneous amenorrhea), or 2. Surgically sterile, or 3. Females of child-bearing potential must have a negative 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
* As a result of medical review, physical examination, or Screening investigations, the Principal Investigator (PI) considers the subject unfit for the study. * Non-elective hospitalization within the 30 days prior to Baseline testing. * Evidence of clinically relevant oral, cardiovascular, gastrointestinal, hepatic, biliary, renal, endocrine, pulmonary, neurologic, psychiatric, immunologic, bone marrow, or skin disorder that contraindicates dosing with SSP-004184AQ. * Iron overload from causes other than transfusional siderosis. * Evidence of severe renal insufficiency, eg, serum creatinine 1.5X above the upper limit of normal or proteinuria greater than 1 gm per day or a calculated glomerular filtration rate \<60mL/min. * Severe iron overload including: 1. T2\* MRI \<10 ms 2. liver iron concentration by FerriScan R2 MRI \>30mg/g liver (dw) * Known sensitivity to magnesium stearate, croscarmellose sodium or SSP-004184AQ. * Platelet count below 100,000/μL or absolute neutrophil count less than 1500/mm3 at Screening. * Insufficient venous access that precludes prescribed blood draws for safety laboratory assessments. * ALT at Screening \>200 IU/L. * Use of any investigational agent within the 30 days prior to the Baseline testing. * Pregnant or lactating females. * Cardiac left ventricular ejection fraction 1. Below the locally determined normal range in the 12 months prior to Screening by echocardiograph or MRI or 2. \<50% at Baseline testing by MRI (echocardiograph is acceptable for LVEF if MRI information is not available).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Liver Iron Concentration (LIC) as Assessed by FerriScan R2 Magnetic Resonance Imaging (MRI) | Baseline, 12 and 24 weeks | 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. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants. |
| Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by FerriScan R2 MRI | Baseline, 12 and 24 weeks | 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. For participants who had a blood transfusion on the MRI exam date, the blood transfusion done immediately prior to the MRI exam date was included in the calculation of daily transfusion intake. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Cardiac T2* Relaxation Rate, an MRI Parameter Used to Estimate Cardiac Iron Load | Baseline, 12 and 24 weeks | The efficacy of SPD602 was assessed by estimating cardiac iron load. T2\* data from cardiac MRI were collected by using standard procedures and used as an estimate of cardiac iron load. T2\* is an MR relaxation parameter that is reported in milliseconds. Iron within a tissue decreases homogeneity of the magnetic field and shortens the T2\* relaxation rate (Anderson, 2001). Low cardiac T2\* values are associated with increased risk of heart failure (Kirk, 2009). A negative change from baseline in the T2\* relaxation rate indicates that iron load increased. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants. |
| Change From Baseline in Serum Ferritin | Baseline, 8 and 16 weeks | Serum ferritin levels were determined from serum biochemistry analyses. A negative change from baseline indicates that serum ferritin decreased. |
| Number of Participants Classified as a Responder by FerriScan R2 MRI Analysis of LIC | 12 and 24 weeks | A responder was defined as a participant whose observed liver iron concentration (LIC) at the measured time point was less than the baseline value. LIC was assessed by abdominal MRI with the FerriScan R2 according to standard procedures. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants. |
| Change From Baseline in LIC as Assessed by R2* MRI | Baseline, 12 and 24 weeks | The efficacy of SPD602 was assessed by determining LIC. Abdominal MRI data were collected by using R2\* standard procedures (liver and pancreas) and used to determine LIC. A negative change from baseline indicates that LIC decreased. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants. |
| Number of Participants Classified as a Responder by R2* MRI Analysis of LIC | 12 and 24 weeks | A responder was defined as a participant whose observed liver iron concentration (LIC) at the measured time point was less than the baseline value. LIC was assessed by abdominal MRI with the R2\* according to standard procedures (liver and pancreas). Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants. |
| Number of Participants Classified as a Responder by R2* MRI Analysis of LIC Adjusted For Transfusional Iron Intake | 12 and 24 weeks | A responder was defined as a participant whose observed liver iron concentration (LIC) at the measured time point was less than the baseline value. LIC was assessed by abdominal MRI with the R2\* according to standard procedures (liver and pancreas), and the results were adjusted for transfusional iron intake. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants. For participants who had a blood transfusion on the MRI exam date, the blood transfusion done immediately prior to the MRI exam date was included in the calculation of daily transfusion intake. |
| Number of Participants Classified as a Responder by Serum Ferritin | 8 and 16 weeks | A responder was defined as a participant whose observed serum ferritin level at the measured time point was less than the baseline value. Serum ferritin levels were determined from serum biochemistry analyses. |
| Number of Participants Classified as a Responder by FerriScan R2 MRI Analysis of LIC Adjusted For Transfusional Iron Intake | 12 and 24 weeks | A responder was defined as a participant whose observed liver iron concentration (LIC) at the measured time point was less than the baseline value. LIC was assessed by abdominal MRI with the FerriScan R2 according to standard procedures, and the results were adjusted for transfusional iron intake. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants. For participants who had a blood transfusion on the MRI exam date, the blood transfusion done immediately prior to the MRI exam date was included in the calculation of daily transfusion intake. |
| Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by R2* MRI | Baseline, 12 and 24 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 (liver and pancreas) and used to determine LIC. A negative change from baseline indicates that LIC decreased. For participants who had a blood transfusion on the MRI exam date, the blood transfusion done immediately prior to the MRI exam date was included in the calculation of daily transfusion intake. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants. |
Countries
Canada, Egypt, Italy, Lebanon, United States
Participant flow
Pre-assignment details
The study started as a double-arm study with once daily (QD) dosing but was amended first to a double-arm study with twice daily (BID) dosing and then to a single-arm study after removing the higher dose. Some participants were enrolled directly to BID dosing, some to QD dosing and then re-enrolled to BID dosing, some completed with QD dosing.
Participants by arm
| Arm | Count |
|---|---|
| SPD602 50mg/kg/Day Participants received SPD602 50mg/kg/day oral dosing either twice daily (BID) or once daily (QD), then BID. | 12 |
| SPD602 75mg/kg/Day Participants received SPD602 75mg/kg/day oral dosing either twice daily (BID) or once daily (QD), then BID. | 7 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 0 | 0 | 1 | 5 |
| Overall Study | Early Study Termination | 9 | 2 | 3 | 3 | 0 | 0 |
| Overall Study | Non-compliance | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Participant Decision | 0 | 0 | 0 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | SPD602 50mg/kg/Day | SPD602 75mg/kg/Day | Total |
|---|---|---|---|
| Age, Continuous | 28.3 years STANDARD_DEVIATION 5.79 | 24.4 years STANDARD_DEVIATION 5.8 | 26.8 years STANDARD_DEVIATION 5.94 |
| Sex: Female, Male Female | 8 Participants | 5 Participants | 13 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 12 | 7 / 7 |
| serious Total, serious adverse events | 2 / 12 | 2 / 7 |
Outcome results
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. For participants who had a blood transfusion on the MRI exam date, the blood transfusion done immediately prior to the MRI exam date was included in the calculation of daily transfusion intake. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
Time frame: Baseline, 12 and 24 weeks
Population: The Full Analysis Set, defined as all participants in the Safety Set who had at least 1 post-baseline primary efficacy assessment. The Safety Set was defined as all participants who had taken at least 1 BID dose of investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPD602 50 mg/kg/d | Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by FerriScan R2 MRI | Week 12, n=5,10 | -6.3 mg Fe/g*dw | Standard Deviation 8.4 |
| SPD602 50 mg/kg/d | Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by FerriScan R2 MRI | Week 24, n=1,2 | -12.8 mg Fe/g*dw | — |
| All Participants With BID Dosing | Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by FerriScan R2 MRI | Week 12, n=5,10 | -6.6 mg Fe/g*dw | Standard Deviation 6.7 |
| All Participants With BID Dosing | Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by FerriScan R2 MRI | Week 24, n=1,2 | -9.3 mg Fe/g*dw | Standard Deviation 5 |
Comparison: Analysis of Week 12 for 50 mg/kg/d dosingp-value: 0.1683paired t-test
Comparison: Analysis of Week 12 for all participants with BID dosingp-value: 0.0123paired t-test
Comparison: Analysis of Week 24 for all participants with BID dosingp-value: 0.2334paired t-test
Primary
Change From Baseline in Liver Iron Concentration (LIC) as 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. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
Time frame: Baseline, 12 and 24 weeks
Population: The Full Analysis Set, defined as all participants in the Safety Set who had at least 1 post-baseline primary efficacy assessment. The Safety Set was defined as all participants who had taken at least 1 BID dose of investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPD602 50 mg/kg/d | Change From Baseline in Liver Iron Concentration (LIC) as Assessed by FerriScan R2 Magnetic Resonance Imaging (MRI) | Week 12, n=5,10 | -3.4 mg Fe/g*dw | Standard Deviation 6.4 |
| SPD602 50 mg/kg/d | Change From Baseline in Liver Iron Concentration (LIC) as Assessed by FerriScan R2 Magnetic Resonance Imaging (MRI) | Week 24, n=1,2 | -5.3 mg Fe/g*dw | — |
| All Participants With BID Dosing | Change From Baseline in Liver Iron Concentration (LIC) as Assessed by FerriScan R2 Magnetic Resonance Imaging (MRI) | Week 12, n=5,10 | -3.8 mg Fe/g*dw | Standard Deviation 5 |
| All Participants With BID Dosing | Change From Baseline in Liver Iron Concentration (LIC) as Assessed by FerriScan R2 Magnetic Resonance Imaging (MRI) | Week 24, n=1,2 | -2.1 mg Fe/g*dw | Standard Deviation 4.5 |
Comparison: Analysis of Week 12 for 50 mg/kg/d dosingp-value: 0.296paired t-test
Comparison: Analysis of Week 12 for all participants with BID dosingp-value: 0.04paired t-test
Comparison: Analysis of Week 24 for all participants with BID dosingp-value: 0.6303paired t-test
Secondary
Change From Baseline in Cardiac T2* Relaxation Rate, an MRI Parameter Used to Estimate Cardiac Iron Load
The efficacy of SPD602 was assessed by estimating cardiac iron load. T2\* data from cardiac MRI were collected by using standard procedures and used as an estimate of cardiac iron load. T2\* is an MR relaxation parameter that is reported in milliseconds. Iron within a tissue decreases homogeneity of the magnetic field and shortens the T2\* relaxation rate (Anderson, 2001). Low cardiac T2\* values are associated with increased risk of heart failure (Kirk, 2009). A negative change from baseline in the T2\* relaxation rate indicates that iron load increased. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
Time frame: Baseline, 12 and 24 weeks
Population: The Full Analysis Set, defined as all participants in the Safety Set who had at least 1 post-baseline primary efficacy assessment. The Safety Set was defined as all participants who had taken at least 1 BID dose of investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPD602 50 mg/kg/d | Change From Baseline in Cardiac T2* Relaxation Rate, an MRI Parameter Used to Estimate Cardiac Iron Load | Week 12, n=5,7 | -0.64 milliseconds | Standard Deviation 3.08 |
| SPD602 50 mg/kg/d | Change From Baseline in Cardiac T2* Relaxation Rate, an MRI Parameter Used to Estimate Cardiac Iron Load | Week 24, n=1,2 | -4.10 milliseconds | — |
| All Participants With BID Dosing | Change From Baseline in Cardiac T2* Relaxation Rate, an MRI Parameter Used to Estimate Cardiac Iron Load | Week 12, n=5,7 | -0.24 milliseconds | Standard Deviation 3.91 |
| All Participants With BID Dosing | Change From Baseline in Cardiac T2* Relaxation Rate, an MRI Parameter Used to Estimate Cardiac Iron Load | Week 24, n=1,2 | -2.60 milliseconds | Standard Deviation 2.121 |
Comparison: Analysis of Week 24 for all participants with BID dosingp-value: 0.3291paired t-test
Comparison: Analysis of Week 12 for 50 mg/kg/d dosingp-value: 0.3202paired t-test
Comparison: Analysis of Week 12 for all participants with BID dosingp-value: 0.4549paired t-test
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 (liver and pancreas) and used to determine LIC. A negative change from baseline indicates that LIC decreased. For participants who had a blood transfusion on the MRI exam date, the blood transfusion done immediately prior to the MRI exam date was included in the calculation of daily transfusion intake. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
Time frame: Baseline, 12 and 24 weeks
Population: The Full Analysis Set, defined as all participants in the Safety Set who had at least 1 post-baseline primary efficacy assessment. The Safety Set was defined as all participants who had taken at least 1 BID dose of investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPD602 50 mg/kg/d | Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by R2* MRI | Week 12, n=5,9 | -6.0 mg Fe/g*dw | Standard Deviation 4.5 |
| SPD602 50 mg/kg/d | Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by R2* MRI | Week 24, n=1,2 | -9.9 mg Fe/g*dw | — |
| All Participants With BID Dosing | Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by R2* MRI | Week 12, n=5,9 | -6.2 mg Fe/g*dw | Standard Deviation 3.2 |
| All Participants With BID Dosing | Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by R2* MRI | Week 24, n=1,2 | -10.5 mg Fe/g*dw | Standard Deviation 0.8 |
Comparison: Analysis of Week 12 for 50 mg/kg/d dosingp-value: 0.0394paired t-test
Comparison: Analysis of Week 12 for all participants with BID dosingp-value: 0.0004paired t-test
Comparison: Analysis of Week 24 for all participants with BID dosingp-value: 0.0332paired t-test
Secondary
Change From Baseline in LIC as Assessed by R2* MRI
The efficacy of SPD602 was assessed by determining LIC. Abdominal MRI data were collected by using R2\* standard procedures (liver and pancreas) and used to determine LIC. A negative change from baseline indicates that LIC decreased. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
Time frame: Baseline, 12 and 24 weeks
Population: The Full Analysis Set, defined as all participants in the Safety Set who had at least 1 post-baseline primary efficacy assessment. The Safety Set was defined as all participants who had taken at least 1 BID dose of investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPD602 50 mg/kg/d | Change From Baseline in LIC as Assessed by R2* MRI | Week 12, n=5,9 | -3.2 mg Fe/g*dw | Standard Deviation 2.3 |
| SPD602 50 mg/kg/d | Change From Baseline in LIC as Assessed by R2* MRI | Week 24, n=1,2 | -2.4 mg Fe/g*dw | — |
| All Participants With BID Dosing | Change From Baseline in LIC as Assessed by R2* MRI | Week 12, n=5,9 | -3.2 mg Fe/g*dw | Standard Deviation 2.1 |
| All Participants With BID Dosing | Change From Baseline in LIC as Assessed by R2* MRI | Week 24, n=1,2 | -3.3 mg Fe/g*dw | Standard Deviation 1.3 |
Comparison: Analysis of Week 12 for 50 mg/kg/d dosingp-value: 0.0365paired t-test
Comparison: Analysis of Week 12 for all participants with BID dosingp-value: 0.0019paired t-test
Comparison: Analysis of Week 24 for all participants with BID dosingp-value: 0.1695paired t-test
Secondary
Change From Baseline in Serum Ferritin
Serum ferritin levels were determined from serum biochemistry analyses. A negative change from baseline indicates that serum ferritin decreased.
Time frame: Baseline, 8 and 16 weeks
Population: The Full Analysis Set, defined as all participants in the Safety Set who had at least 1 post-baseline primary efficacy assessment. The Safety Set was defined as all participants who had taken at least 1 BID dose of investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SPD602 50 mg/kg/d | Change From Baseline in Serum Ferritin | Week 8, n=5,11 | -762.63 ng/mL | Standard Deviation 2100.683 |
| SPD602 50 mg/kg/d | Change From Baseline in Serum Ferritin | Week 16, n=1,4 | 586.47 ng/mL | — |
| All Participants With BID Dosing | Change From Baseline in Serum Ferritin | Week 8, n=5,11 | -568.08 ng/mL | Standard Deviation 1426.687 |
| All Participants With BID Dosing | Change From Baseline in Serum Ferritin | Week 16, n=1,4 | 137.63 ng/mL | Standard Deviation 972.97 |
Comparison: Analysis of Week 8 for 50 mg/kg/d dosingp-value: 0.6703paired t-test
Comparison: Analysis of Week 8 for all participants with BID dosingp-value: 0.2618paired t-test
Comparison: Analysis of Week 16 for all participants with BID dosingp-value: 0.7679paired t-test
Secondary
Number of Participants Classified as a Responder by FerriScan R2 MRI Analysis of LIC
A responder was defined as a participant whose observed liver iron concentration (LIC) at the measured time point was less than the baseline value. LIC was assessed by abdominal MRI with the FerriScan R2 according to standard procedures. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
Time frame: 12 and 24 weeks
Population: The Full Analysis Set, defined as all participants in the Safety Set who had at least 1 post-baseline primary efficacy assessment. The Safety Set was defined as all participants who had taken at least 1 BID dose of investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SPD602 50 mg/kg/d | Number of Participants Classified as a Responder by FerriScan R2 MRI Analysis of LIC | Week 12, n=5,10 | 4 participants |
| SPD602 50 mg/kg/d | Number of Participants Classified as a Responder by FerriScan R2 MRI Analysis of LIC | Week 24, n=1,2 | 1 participants |
| All Participants With BID Dosing | Number of Participants Classified as a Responder by FerriScan R2 MRI Analysis of LIC | Week 12, n=5,10 | 8 participants |
| All Participants With BID Dosing | Number of Participants Classified as a Responder by FerriScan R2 MRI Analysis of LIC | Week 24, n=1,2 | 1 participants |
Secondary
Number of Participants Classified as a Responder by FerriScan R2 MRI Analysis of LIC Adjusted For Transfusional Iron Intake
A responder was defined as a participant whose observed liver iron concentration (LIC) at the measured time point was less than the baseline value. LIC was assessed by abdominal MRI with the FerriScan R2 according to standard procedures, and the results were adjusted for transfusional iron intake. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants. For participants who had a blood transfusion on the MRI exam date, the blood transfusion done immediately prior to the MRI exam date was included in the calculation of daily transfusion intake.
Time frame: 12 and 24 weeks
Population: The Full Analysis Set, defined as all participants in the Safety Set who had at least 1 post-baseline primary efficacy assessment. The Safety Set was defined as all participants who had taken at least 1 BID dose of investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SPD602 50 mg/kg/d | Number of Participants Classified as a Responder by FerriScan R2 MRI Analysis of LIC Adjusted For Transfusional Iron Intake | Week 12, n=5,10 | 4 participants |
| SPD602 50 mg/kg/d | Number of Participants Classified as a Responder by FerriScan R2 MRI Analysis of LIC Adjusted For Transfusional Iron Intake | Week 24, n=1,2 | 1 participants |
| All Participants With BID Dosing | Number of Participants Classified as a Responder by FerriScan R2 MRI Analysis of LIC Adjusted For Transfusional Iron Intake | Week 12, n=5,10 | 8 participants |
| All Participants With BID Dosing | Number of Participants Classified as a Responder by FerriScan R2 MRI Analysis of LIC Adjusted For Transfusional Iron Intake | Week 24, n=1,2 | 1 participants |
Secondary
Number of Participants Classified as a Responder by R2* MRI Analysis of LIC
A responder was defined as a participant whose observed liver iron concentration (LIC) at the measured time point was less than the baseline value. LIC was assessed by abdominal MRI with the R2\* according to standard procedures (liver and pancreas). Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
Time frame: 12 and 24 weeks
Population: The Full Analysis Set, defined as all participants in the Safety Set who had at least 1 post-baseline primary efficacy assessment. The Safety Set was defined as all participants who had taken at least 1 BID dose of investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SPD602 50 mg/kg/d | Number of Participants Classified as a Responder by R2* MRI Analysis of LIC | Week 12, n=5,9 | 5 participants |
| SPD602 50 mg/kg/d | Number of Participants Classified as a Responder by R2* MRI Analysis of LIC | Week 24, n=1,2 | 1 participants |
| All Participants With BID Dosing | Number of Participants Classified as a Responder by R2* MRI Analysis of LIC | Week 12, n=5,9 | 9 participants |
| All Participants With BID Dosing | Number of Participants Classified as a Responder by R2* MRI Analysis of LIC | Week 24, n=1,2 | 2 participants |
Secondary
Number of Participants Classified as a Responder by R2* MRI Analysis of LIC Adjusted For Transfusional Iron Intake
A responder was defined as a participant whose observed liver iron concentration (LIC) at the measured time point was less than the baseline value. LIC was assessed by abdominal MRI with the R2\* according to standard procedures (liver and pancreas), and the results were adjusted for transfusional iron intake. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants. For participants who had a blood transfusion on the MRI exam date, the blood transfusion done immediately prior to the MRI exam date was included in the calculation of daily transfusion intake.
Time frame: 12 and 24 weeks
Population: The Full Analysis Set, defined as all participants in the Safety Set who had at least 1 post-baseline primary efficacy assessment. The Safety Set was defined as all participants who had taken at least 1 BID dose of investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SPD602 50 mg/kg/d | Number of Participants Classified as a Responder by R2* MRI Analysis of LIC Adjusted For Transfusional Iron Intake | Week 12, n=5,9 | 5 participants |
| SPD602 50 mg/kg/d | Number of Participants Classified as a Responder by R2* MRI Analysis of LIC Adjusted For Transfusional Iron Intake | Week 24, n=1,2 | 1 participants |
| All Participants With BID Dosing | Number of Participants Classified as a Responder by R2* MRI Analysis of LIC Adjusted For Transfusional Iron Intake | Week 12, n=5,9 | 9 participants |
| All Participants With BID Dosing | Number of Participants Classified as a Responder by R2* MRI Analysis of LIC Adjusted For Transfusional Iron Intake | Week 24, n=1,2 | 2 participants |
Secondary
Number of Participants Classified as a Responder by Serum Ferritin
A responder was defined as a participant whose observed serum ferritin level at the measured time point was less than the baseline value. Serum ferritin levels were determined from serum biochemistry analyses.
Time frame: 8 and 16 weeks
Population: The Full Analysis Set, defined as all participants in the Safety Set who had at least 1 post-baseline primary efficacy assessment. The Safety Set was defined as all participants who had taken at least 1 BID dose of investigational product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SPD602 50 mg/kg/d | Number of Participants Classified as a Responder by Serum Ferritin | Week 8, n=5,11 | 3 participants |
| SPD602 50 mg/kg/d | Number of Participants Classified as a Responder by Serum Ferritin | Week 16, n=1,4 | 0 participants |
| All Participants With BID Dosing | Number of Participants Classified as a Responder by Serum Ferritin | Week 8, n=5,11 | 8 participants |
| All Participants With BID Dosing | Number of Participants Classified as a Responder by Serum Ferritin | Week 16, n=1,4 | 1 participants |