Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02041299
Recruitment Status : Terminated (Difficulties with additional recruitment as pool of potential patients was exhausted, and sufficient information for determination of study outcome measure was already obtained)
First Posted : January 22, 2014
Results First Posted : August 10, 2021
Last Update Posted : August 10, 2021
Sponsor:
Information provided by (Responsible Party):
Chiesi Canada Corp ( ApoPharma )

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.

Condition or disease Intervention/treatment Phase
Iron Overload Sickle Cell Disease Other Anemias Drug: Deferiprone Drug: Deferoxamine Phase 4

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 230 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Efficacy and Safety of Ferriprox® for the Treatment of Transfusional Iron Overload in Patients With Sickle Cell Disease or Other Anemias
Actual Study Start Date : April 17, 2014
Actual Primary Completion Date : April 20, 2019
Actual Study Completion Date : June 18, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anemia Iron

Arm Intervention/treatment
Experimental: Deferiprone
Patients randomized to the deferiprone arm will be prescribed either tablets or liquid medication. Deferiprone is taken orally, at a dosage that is calculated in terms of milligrams per kilogram of body weight (mg/kg) and is divided into 3 equal doses taken approximately 8 hours apart. The daily dosage is 75 mg/kg (25 mg/kg per dose) for patients with less severe iron load, and 99 mg/kg (33 mg/kg per dose) for those with more severe iron load.
Drug: Deferiprone
Other Names:
  • Ferriprox tablets
  • Deferiprone oral solution

Active Comparator: Deferoxamine
Patients randomized to the deferoxamine arm will be prescribed the drug as per the approved US prescribing information. Deferoxamine is administered as a subcutaneous infusion over 8-12 hours, 5 to 7 days a week. The dosage is 20 mg/kg (children) or 40 mg/kg (adults) in patients with less severe iron load, and up to 40 mg/kg (children) or 50 mg/kg (adults) in those with more severe iron load.
Drug: Deferoxamine



Primary Outcome Measures :
  1. Change From Baseline in Liver Iron Concentration (LIC) [ Time Frame: Change from baseline to Week 52 ]
    LIC was measured by MRI. A score >7 mg/g dw is indicative of iron overload.


Secondary Outcome Measures :
  1. Change From Baseline in Cardiac Iron [ Time Frame: Change from baseline to Week 52 ]
    Cardiac iron is measured by MRI in milliseconds (ms). A score of less than 20 ms is indicative of cardiac iron overload.

  2. Change From Baseline in Serum Ferritin [ Time Frame: Change from baseline to Week 52 ]
    Serum ferritin provides a measure of iron level in the blood. Normal levels of serum ferritin are under 300 µg/L for females and 400 µg/L for males.

  3. Change in Patient-reported Quality of Life, as Measured by the Short Form Health Survey (SF-36) or the Child Health Questionnaire (CHQ-PF50). [ Time Frame: Change from baseline to Week 52 ]
    Adult patients completed the SF-36 questionnaire and minors completed the CHQ-PF50. These questionnaires yield a profile of functional health and well-being, based on 8 scales of physical and mental health measures: Physical Functioning, Role Limitations due to Physical Health, Bodily Pain, General Health Perceptions, Vitality, Social Functioning, Role Limitations due to Emotional Problems, and Mental Health (MH), and summary scores are produced for physical well-being and mental well-being. The summaries are scored from 0-100, with higher scores reflecting better outcomes.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02041299


Locations
Show Show 33 study locations
Sponsors and Collaborators
ApoPharma
Investigators
Layout table for investigator information
Principal Investigator: Janet Kwiatkowski, MD Children's Hospital of Philadelphia
  Study Documents (Full-Text)

Documents provided by Chiesi Canada Corp ( ApoPharma ):
Study Protocol  [PDF] May 1, 2017
Statistical Analysis Plan  [PDF] December 3, 2018

Layout table for additonal information
Responsible Party: ApoPharma
ClinicalTrials.gov Identifier: NCT02041299    
Other Study ID Numbers: LA38-0411
First Posted: January 22, 2014    Key Record Dates
Results First Posted: August 10, 2021
Last Update Posted: August 10, 2021
Last Verified: July 2021
Keywords provided by Chiesi Canada Corp ( ApoPharma ):
sickle cell disease
Iron overload
Deferiprone
Ferriprox
deferoxamine
Chelation
Additional relevant MeSH terms:
Layout table for MeSH terms
Anemia
Anemia, Sickle Cell
Iron Overload
Hematologic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hemoglobinopathies
Genetic Diseases, Inborn
Iron Metabolism Disorders
Metabolic Diseases
Deferiprone
Deferoxamine
Iron Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Siderophores