Clinical Trial: Pharmacokinetics of SSP-004184 in the Treatment of Chronic Iron Overload Requiring Chelation Therapy

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Phase 2, 24 Week, Open Label, Multi-Center Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SSP-004184 (SPD602) in the Treatment of Chronic Iron Overload Requiring

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.


Detailed Summary:
Sponsor: Shire

Current Primary Outcome:

  • Change From Baseline in Liver Iron Concentration (LIC) as Assessed by FerriScan R2 Magnetic Resonance Imaging (MRI) [ Time Frame: 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 [ Time Frame: 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.


Original Primary Outcome:

  • Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC 0→∞) of FBS0701 [ Time Frame: Assessed over an 8-hour time period starting post-dose at either Week 8, 12 or 16 ]
  • Maximum Plasma Concentration (Cmax) of FBS0701 [ Time Frame: Assessed over an 8-hour time period starting post-dose at either Week 8, 12 or 16 ]


Current Secondary Outcome:

  • Change From Baseline in LIC as Assessed by R2* MRI [ Time Frame: 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.
  • Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by R2* MRI [ Time Frame: 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.
  • Change From Baseline in Cardiac T2* Relaxation Rate, an MRI Parameter Used to Estimate Cardiac Iron Load [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
  • Number of Participants Classified as a Responder by FerriScan R2 MRI Analysis of LIC Adjusted For Transfusional Iron Intake [ Time Frame: 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.
  • Number of Participants Classified as a Responder by R2* MRI Analysis of LIC [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 8 and 16 weeks ]
    A responder was defined as a participant whose observed ser

    Original Secondary Outcome: Liver iron concentration change as determined by MRI [ Time Frame: 12 and 24 weeks ]

    Information By: Shire

    Dates:
    Date Received: May 22, 2012
    Date Started: September 2012
    Date Completion:
    Last Updated: July 22, 2015
    Last Verified: August 2014