Iron OverloadPhase 4FIRSTNCT02041299
Efficacy and Safety of Ferriprox® in Patients With Sickle Cell Disease or Other Anemias
A Phase 4 study testing Deferiprone and Deferoxamine in people with Iron Overload and Sickle Cell Disease, run by ApoPharma at 33 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Iron Overload, Sickle Cell Disease, Other Anemias
- What is being tested?
- Deferiprone and Deferoxamine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 230 participants
- Where
- 33 sitesin 8 countries
- Study dates
- 17 Apr 2014to 18 Jun 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female ≥ 2 years of age;
- 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);
- Baseline LIC >7 mg/g dw (measured by MRI);
- Patients who have received no less than 20 transfusions of RBCs;
- 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
Who cannot join
- Thalassemia syndromes;
- Myelodysplastic syndrome (MDS) or myelofibrosis;
- Diamond Blackfan anemia;
- Primary bone marrow failure;
- Baseline LIC >30 mg/g dw (measured by MRI);
- Unable or unwilling to undergo a 7 day washout period if currently being treated with deferiprone or deferoxamine or deferasirox;
Show all 17Show fewer
- Previous discontinuation of treatment with deferiprone or deferoxamine due to adverse events;
- History or presence of hypersensitivity or idiosyncratic reaction to deferiprone or deferoxamine;
- Treated with hydroxyurea within 30 days;
- History of malignancy;
- 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);
- 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;
- Clinically significant abnormal 12-lead ECG findings;
- Cardiac MRI T2* <10ms;
- Myocardial infarction, cardiac arrest or cardiac failure within 1 year before screening/baseline visit;
- Unable to undergo MRI
- 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
Trial locations and contacts
33 sites in 8 countries.
33 sites in 8 countries
United States8 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
Medical University of South Carolina
Charleston, South Carolina, 29425
University of Illinois at Chicago
Chicago, Illinois, 60612
Children's Hospital of Michigan
Detroit, Michigan, 48201
Children's Hospital
New Orleans, Louisiana, 70118
Children's Hospital Oakland
Oakland, California, 94609
The Children's Hospital of Philadephia
Philadelphia, Pennsylvania, 19104-4399
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Egypt6 sites
Mansoura University Children's Hospital
Al Mansurah
Alexandria University
Alexandria
Zagazig University
Alexandria
Ains Shams University
Cairo
Cairo University
Cairo
Pediatric Hospital of Cairo University
Cairo
Brazil5 sites
Centro Infantil Boldrini
Campinas
Hospital de Clínicas de Porto Alegre-HCPA,
Rio Branco, 90035-903
Instituto Estadual de Hematologia Arthur Siqueira Cavalcanti - HEMORIO
Rio de Janeiro, 20211-030
Casa de Saúde Santa Marcelina
São Paulo
Universidade Federal de São Paulo
São Paulo
United Kingdom4 sites
Hammersmith Hospital
London, W12 0HS
Barts and The London
London
Evelina Children's Hospital
London
Imperial College Healthcare NHS Trust
London
Saudi Arabia3 sites
Asser Central Hospital
Abhā
King Abdulaziz University Hospital
Jeddah, Western Region, 80215
King Khalid University Hospital
Riyadh
Tunisia3 sites
Farhat Hached Hospital, Hematology Department
Sousse
National Center for Bone Marrow Transplantation
Tunis, Bad Saadoun
Principal Military Hospital of Instruction of Tunis
Tunis
Turkey (Türkiye)3 sites
Cukurova University
Adana
Hacettepe University
Ankara
Istanbul University
Istanbul
About this study
Official title: The Efficacy and Safety of Ferriprox® for the Treatment of Transfusional Iron Overload in Patients With Sickle Cell Disease or Other Anemias
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.
Read the 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.
- Conditions
- Iron Overload, Sickle Cell Disease, Other Anemias
- Being tested
- Deferiprone, Deferoxamine
- Keywords
- sickle cell disease, Iron overload, Deferiprone, Ferriprox, deferoxamine, Chelation
- Medical subject headings
- Iron Overload, Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DeferiproneDrug
Also called Ferriprox tablets, Deferiprone oral solution
DeferoxamineDrug
| Study group | Role | What they receive |
|---|---|---|
| Deferiprone | Experimental | 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. Receives: Drug: Deferiprone |
| Deferoxamine | Active comparator | 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. Receives: Drug: Deferoxamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Liver Iron Concentration (LIC)
LIC was measured by MRI. A score >7 mg/g dw is indicative of iron overload.
Measured: Change from baseline to Week 52
Secondary outcomes (3)
Change From Baseline in Cardiac Iron
Cardiac iron is measured by MRI in milliseconds (ms). A score of less than 20 ms is indicative of cardiac iron overload.
Measured: Change from baseline to Week 52
Change From Baseline in Serum Ferritin
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.
Measured: Change from baseline to Week 52
Change in Patient-reported Quality of Life, as Measured by the Short Form Health Survey (SF-36) or the Child Health Questionnaire (CHQ-PF50).
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.
Measured: Change from baseline to Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2014 (estimated)
- Study start17 Apr 2014
- Primary completion20 Apr 2019
- Study completion18 Jun 2019
Why it stopped: Difficulties with additional recruitment as pool of potential patients was exhausted, and sufficient information for determination of study outcome measure was already obtained
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Iron OverloadStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 230 participants (actual)
Sponsor and investigators
- Lead sponsor
- ApoPharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janet Kwiatkowski, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02041299
- Sponsor's protocol ID
- LA38-0411
- Acronym
- FIRST
- Status last verified
- Jul 2021
- First submitted
- 15 Jan 2014
- Last updated
- 10 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Hamdy M, El-Beshlawy A, Verissimo MPA, Kanter J, Inusa B, Williams S, Lee D, Temin NT, Fradette C, Tricta F, Ebeid FSE, Kwiatkowski JL, Elalfy MS. Deferiprone versus deferoxamine for transfusional iron overload in sickle cell disease and other anemias: Pediatric subgroup analysis of the randomized, open-label FIRST study. Pediatr Blood Cancer. 2024 Jan;71(1):e30711. doi: 10.1002/pbc.30711. Epub 2023 Oct 9.
PubMed 37807937Kwiatkowski JL, Hamdy M, El-Beshlawy A, Ebeid FSE, Badr M, Alshehri A, Kanter J, Inusa B, Adly AAM, Williams S, Kilinc Y, Lee D, Tricta F, Elalfy MS. Deferiprone vs deferoxamine for transfusional iron overload in SCD and other anemias: a randomized, open-label noninferiority study. Blood Adv. 2022 Feb 22;6(4):1243-1254. doi: 10.1182/bloodadvances.2021004938.
PubMed 34847228
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy and Safety of Ferriprox® for the Treatment of Transfusional Iron Overload in Patients With Sickle Cell Disease or Other Anemias
- ClinicalTrials.gov ID
- NCT02041299
- Acronym / sponsor ID
- FIRST / LA38-0411
- Conditions
- Iron Overload, Sickle Cell Disease, Other Anemias
- Keywords
- sickle cell disease, Iron overload, Deferiprone, Ferriprox, deferoxamine, Chelation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulties with additional recruitment as pool of potential patients was exhausted, and sufficient information for determination of study outcome measure was already obtained
- Enrolment
- 230 participants (actual)
- Lead sponsor
- ApoPharmaIndustry (pharma, biotech, devices)
- Study start
- 17 Apr 2014 (actual)
- Primary completion
- 20 Apr 2019 (actual)
- Study completion
- 18 Jun 2019 (actual)
- First posted
- 22 Jan 2014 (estimated)
- Results
- Posted 10 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Deferiprone | Experimental | Drug: DeferipronePatients 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. |
| Deferoxamine | Active comparator | Drug: DeferoxaminePatients 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. |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female ≥ 2 years of age;
- 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);
- Baseline LIC >7 mg/g dw (measured by MRI);
- Patients who have received no less than 20 transfusions of RBCs;
- 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
Key exclusion criteria (17 listed)
- Thalassemia syndromes;
- Myelodysplastic syndrome (MDS) or myelofibrosis;
- Diamond Blackfan anemia;
- Primary bone marrow failure;
- Baseline LIC >30 mg/g dw (measured by MRI);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DeferiproneAlso: Ferriprox tablets, Deferiprone oral solution | Drug | Deferiprone |
| Deferoxamine | Drug | Deferoxamine |
Primary outcome
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.
3 secondary outcomes
Change From Baseline in Cardiac Iron
Time frame: Change from baseline to Week 52
Change From Baseline in Serum Ferritin
Time frame: Change from baseline to Week 52
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37807937Hamdy M, El-Beshlawy A, Verissimo MPA, Kanter J, Inusa B, Williams S, Lee D, Temin NT, Fradette C, Tricta F, Ebeid FSE, Kwiatkowski JL, Elalfy MS. Deferiprone versus deferoxamine for transfusional iron overload in sickle cell disease and other anemias: Pediatric subgroup analysis of the randomized, open-label FIRST study. Pediatr Blood Cancer. 2024 Jan;71(1):e30711. doi: 10.1002/pbc.30711. Epub 2023 Oct 9.
- Derived from this study: PubMed 34847228Kwiatkowski JL, Hamdy M, El-Beshlawy A, Ebeid FSE, Badr M, Alshehri A, Kanter J, Inusa B, Adly AAM, Williams S, Kilinc Y, Lee D, Tricta F, Elalfy MS. Deferiprone vs deferoxamine for transfusional iron overload in SCD and other anemias: a randomized, open-label noninferiority study. Blood Adv. 2022 Feb 22;6(4):1243-1254. doi: 10.1182/bloodadvances.2021004938.
Related trials for Iron Overload
Active, not recruitingPhase 2
Treatment of Hemochromatosis
Hemochromatosis
Active, not recruitingObservational study
Ethnic Differences in Iron Absorption (FeGenes)
Anemia, Iron Deficiency, Iron Overload
Active, not recruitingObservational study
Heme and Non-heme Iron Intakes, Gut Microbiota, and Influence on Host Iron Absorption
Anemia, Iron Deficiency, Iron Overload
Active, not recruitingPhase 2
Efficacy and Safety of Vamifeport in Adult Participants With Homeostatic Iron Regulator Gene (HFE)-Related Hereditary Hemochromatosis
Homeostatic Iron Regulator Gene-related Hereditary Hemochromatosis
Not yet recruitingObservational study
Native T1 Mapping and ECV in Chronic Hemolytic Anemia
Hemolytic Anemia, Thalassemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janet Kwiatkowski, MD principal investigator
Children's Hospital of Philadelphia
33 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Deferiprone and Deferoxamine in people with Iron Overload and Sickle Cell Disease, run by ApoPharma at 33 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 33 sites in United States, Egypt, Brazil, United Kingdom, Saudi Arabia and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Liver Iron Concentration (LIC) (time frame: Change from baseline to Week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02041299, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2021.