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Efficacy and Safety of Ferriprox® in Patients With Sickle Cell Disease or Other Anemias (FIRST)

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ClinicalTrials.gov Identifier: NCT02041299
Recruitment Status : Unknown
Verified January 2019 by ApoPharma.
Recruitment status was:  Recruiting
First Posted : January 22, 2014
Last Update Posted : January 14, 2019
Sponsor:
Information provided by (Responsible Party):
ApoPharma

Tracking Information
First Submitted Date  ICMJE January 15, 2014
First Posted Date  ICMJE January 22, 2014
Last Update Posted Date January 14, 2019
Study Start Date  ICMJE March 2014
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 17, 2014)
Change in liver iron concentration, as measured in mg/g dry weight (dw) using MRI [ Time Frame: Change from baseline to Week 52 ]
Without effective iron chelation therapy, transfusion-dependent patients experience a progressive increase in Liver Iron Concentration (LIC). High LIC increases the risk of iron-induced toxicity such as cardiac disease, hepatic fibrosis, diabetes mellitus, and death.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 6, 2018)
  • Change in patient-reported quality of life, as measured by SF-36 or Child Health Questionnaire [ Time Frame: Change from baseline to Week 52 ]
    Adults patients will complete the SF-36 questionnaire and minors will complete the CHQ, in order to provide a profile of functional health and well-being.
  • Change in cardiac MRI T2*, measured in milliseconds (ms) [ Time Frame: Change from baseline to Week 52 ]
    MRI T2* provides a measure of iron levels in the heart
  • Change in serum ferritin, measured in mcg/L [ Time Frame: Change from baseline to Week 52 ]
    Serum ferritin provides a measure of iron level in the blood
  • Occurrence of adverse events [ Time Frame: From first dose (Baseline visit) to last study visit (Week 52 or early termination) ]
    Number of participants in each group with AEs, by frequency, nature, severity, time to onset, and duration of AEs
  • Frequency of serious adverse events (SAEs) [ Time Frame: From first dose (Baseline visit) to last study visit (Week 52 or early termination) ]
    Number of participants in each group with SAEs
  • Hematology assessments [ Time Frame: Assessed at baseline, weekly (till week 26), biweekly (after week 26), monthly and at Weeks 12, 26, 40, and 52 (or early termination) ]
    Change from baseline at each visit and change from baseline at end of study for hemoglobin, total WBC, ANC, and platelets
  • Blood clinical biochemistry assessments [ Time Frame: Assessed at baseline, monthly and Weeks 12, 26, 40, and 52 (or early termination) ]
    Change from baseline at each visit and change from baseline at end of study for total protein; GGT; lactate dehydrogenase (LDH); sodium, potassium, chloride, glucose (fasting at screening visit only); total, direct and indirect bilirubin; AST; ALT; albumin; blood urea nitrogen; calcium; creatinine; uric acid; alkaline phosphatase; and amylase
  • Abnormal and clinically significant findings in 12-lead ECG [ Time Frame: Screening, Week 26, and end of study (Week 52 or early termination) visits ]
    Change in abnormal or clinically significant ECG parameters from screening to each later time point
  • Discontinuations due to AEs [ Time Frame: From first dose (Baseline visit) to last study visit (Week 52 or early termination) ]
    Number of participants in each group who discontinued from the study due to AEs
Original Secondary Outcome Measures  ICMJE
 (submitted: January 17, 2014)
  • Change in patient-reported quality of life, as measured by SF-36 or Child Health Questionnaire [ Time Frame: Change from baseline to Week 52 ]
    Adults patients will complete the SF-36 questionnaire and minors will complete the CHQ, in order to provide a profile of functional health and well-being.
  • Change in cardiac MRI T2*, measured in milliseconds (ms) [ Time Frame: Change from baseline to Week 52 ]
    MRI T2* provides a measure of iron levels in the heart
  • Change in serum ferritin, measured in mcg/L [ Time Frame: Change from baseline to Week 52 ]
    Serum ferritin provides a measure of iron level in the blood
  • Occurrence of adverse events [ Time Frame: From first dose (Baseline visit) to last study visit (Week 52 or early termination) ]
    Number of participants in each group with AEs, by frequency, nature, severity, time to onset, and duration of AEs
  • Frequency of serious adverse events (SAEs) [ Time Frame: From first dose (Baseline visit) to last study visit (Week 52 or early termination) ]
    Number of participants in each group with SAEs
  • Hematology assessments [ Time Frame: Assessed at baseline, weekly, monthly and at Weeks 12, 26, 40, and 52 (or early termination) ]
    Change from baseline at each visit and change from baseline at end of study for hemoglobin, total WBC, ANC, and platelets
  • Blood clinical biochemistry assessments [ Time Frame: Assessed at baseline, monthly and Weeks 12, 26, 40, and 52 (or early termination) ]
    Change from baseline at each visit and change from baseline at end of study for total protein; GGT; lactate dehydrogenase (LDH); sodium, potassium, chloride, glucose (fasting at screening visit only); total, direct and indirect bilirubin; AST; ALT; albumin; blood urea nitrogen; calcium; creatinine; uric acid; alkaline phosphatase; and amylase
  • Abnormal and clinically significant findings in 12-lead ECG [ Time Frame: Screening, Week 26, and end of study (Week 52 or early termination) visits ]
    Change in abnormal or clinically significant ECG parameters from screening to each later time point
  • Discontinuations due to AEs [ Time Frame: From first dose (Baseline visit) to last study visit (Week 52 or early termination) ]
    Number of participants in each group who discontinued from the study due to AEs
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Ferriprox® in Patients With Sickle Cell Disease or Other Anemias
Official Title  ICMJE The Efficacy and Safety of Ferriprox® for the Treatment of Transfusional Iron Overload in Patients With Sickle Cell Disease or Other Anemias
Brief Summary This research is being done so that we can look at the safety and efficacy of deferiprone in people with sickle cell disease or other anemias. Deferiprone is a drug that removes iron from the body. We will be comparing deferiprone with deferoxamine, another drug that removes iron from the body.
Detailed Description

Deferiprone (brand name Ferriprox®) is an iron chelator that is approved in the United States and over 60 other countries for the treatment of iron overload in patients with thalassemia, when other treatments are inadequate. This study has been designed to evaluate the efficacy, safety, and tolerability of deferiprone vs. deferoxamine in patients who have SCD or other anemias, and who require chelation because of the extra iron they are taking in through blood transfusions.

About 300 people from North America, South America, Europe, and the Middle East will take part in this study. Participants will be randomized in a 2:1 ratio to receive therapy for 52 weeks with either deferiprone or deferoxamine, another type of iron chelator. Patients who are randomized to the deferiprone group can choose to get the drug as either tablets or liquid, and must take it three times daily. Patients who are randomized to the deferoxamine group will receive it as a subcutaneous infusion that lasts from 8 to 12 hours and is given 5 to 7 days per week. For both drugs, the starting dosage is based on how much extra iron they have taken in through transfusions in the last 3 months and on the severity of iron load, as measured by serum ferritin levels in the blood and by the amount of iron in the liver and the heart. For deferiprone, the starting dosage will be increased each week over the first 3 weeks; and for both drugs, the dosage may be adjusted up or down during the study based on the level of iron overload and on safety considerations.

Patients will need to have their blood count checked every week for the first 26 weeks, then every other week for the remaining 26 weeks; they will also have to give a blood sample for more detailed safety testing every month; and to give a blood sample for the measurement of serum ferritin every 3 months. Every six months, they will undergo an ECG and an MRI scan, and will be asked to complete a quality of life survey.

At the end of the 52 weeks, participants will be invited to enter a 2-year study in which all patients will receive deferiprone, including those who were randomized to receive deferoxamine in the first year.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Iron Overload
  • Sickle Cell Disease
  • Other Anemias
Intervention  ICMJE
  • Drug: Deferiprone
    Other Names:
    • Ferriprox tablets
    • Deferiprone oral solution
  • Drug: Deferoxamine
Study Arms  ICMJE
  • Experimental: Deferiprone
    Patients randomized to the deferiprone arm will be prescribed either tablets or liquid medication.
    Intervention: Drug: Deferiprone
  • Active Comparator: Deferoxamine
    Patients randomized to the deferoxamine arm will be prescribed the drug as per the approved US prescribing information.
    Intervention: Drug: Deferoxamine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: January 17, 2014)
300
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2019
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female ≥ 2 years of age;
  2. Have sickle cell disease (confirmed by Hb electrophoresis or more specific tests) or other conditions with iron overload from repeated blood transfusions (see exclusion criteria for exceptions);
  3. Baseline LIC >7 mg/g dw (measured by MRI);
  4. Patients who have received no less than 20 transfusions of RBCs;
  5. Patients who have received at least 1 transfusion per year in the last 2 years and who are expected to have a continuing requirement (based on Investigator's judgement) during the duration of the trial

Exclusion Criteria:

  1. Thalassemia syndromes;
  2. Myelodysplastic syndrome (MDS) or myelofibrosis;
  3. Diamond Blackfan anemia;
  4. Primary bone marrow failure;
  5. Baseline LIC >30 mg/g dw (measured by MRI);
  6. Unable or unwilling to undergo a 7 day washout period if currently being treated with deferiprone or deferoxamine or deferasirox;
  7. Previous discontinuation of treatment with deferiprone or deferoxamine due to adverse events;
  8. History or presence of hypersensitivity or idiosyncratic reaction to deferiprone or deferoxamine;
  9. Treated with hydroxyurea within 30 days;
  10. History of malignancy;
  11. Evidence of abnormal liver function (serum ALT level(s) > 5 times upper limit of normal at screening or creatinine levels >2 times upper limit of normal at screening);
  12. A serious, unstable illness, as judged by the Investigator, during the past 3 months before screening/baseline visit including but not limited to: hepatic, renal, gastro-enterologic, respiratory, cardiovascular, endocrinologic, neurologic or immunologic disease;
  13. Clinically significant abnormal 12-lead ECG findings;
  14. Cardiac MRI T2* <10ms;
  15. Myocardial infarction, cardiac arrest or cardiac failure within 1 year before screening/baseline visit;
  16. Unable to undergo MRI
  17. Presence of metallic objects such as artificial joints, inner ear (cochlear) implants, brain aneurysm clips, pacemakers, and metallic foreign bodies in the eye or other body areas that would prevent use of MRI imaging
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil,   Canada,   Egypt,   Qatar,   Saudi Arabia,   Tunisia,   Turkey,   United Kingdom,   United States
Removed Location Countries France
 
Administrative Information
NCT Number  ICMJE NCT02041299
Other Study ID Numbers  ICMJE LA38-0411
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party ApoPharma
Study Sponsor  ICMJE ApoPharma
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Janet Kwiatkowski, MD Children's Hospital of Philadelphia
PRS Account ApoPharma
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP