Clinical trial NCT02041299: Efficacy and Safety of Ferriprox® in Patients With Sickle Cell Disease or Other Anemias
Official title: The Efficacy and Safety of Ferriprox® for the Treatment of Transfusional Iron Overload in Patients With Sickle Cell Disease or Other Anemias
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Iron Overload
Sickle Cell Disease
Other Anemias
Keywords: sickle cell disease
Iron overload
Deferiprone
Ferriprox
deferoxamine
Chelation
Lead sponsor: Chiesi Canada Corp
Sponsor class: INDUSTRY
First posted: 2014-01-22
Enrollment: 230
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Change From Baseline in Liver Iron Concentration (LIC)
timeFrame: Change from baseline to Week 52
Secondary outcomes:
measure: Change From Baseline in Cardiac Iron
timeFrame: Change from baseline to Week 52
measure: Change From Baseline in Serum Ferritin
timeFrame: Change from baseline to Week 52
measure: Change in Patient-reported Quality of Life, as Measured by the Short Form Health Survey (SF-36) or the Child Health Questionnaire (CHQ-PF50).
timeFrame: Change from baseline to Week 52
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Children's Hospital Oakland
state: California
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: New Orleans
country: United States
facility: Children's Hospital
state: Louisiana
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadephia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Campinas
country: Brazil
facility: Centro Infantil Boldrini
city: Rio Branco
country: Brazil
facility: Hospital de Clínicas de Porto Alegre-HCPA,
city: Rio de Janeiro
country: Brazil
facility: Instituto Estadual de Hematologia Arthur Siqueira Cavalcanti - HEMORIO
city: São Paulo
country: Brazil
facility: Casa de Saúde Santa Marcelina
city: São Paulo
country: Brazil
facility: Universidade Federal de São Paulo
city: Toronto
country: Canada
facility: Hospital for Sick Kids
state: Ontario
city: Alexandria
country: Egypt
facility: Alexandria University
city: Alexandria
country: Egypt
facility: Zagazig University
city: Cairo
country: Egypt
facility: Ains Shams University
city: Cairo
country: Egypt
facility: Cairo University
city: Cairo
country: Egypt
facility: Pediatric Hospital of Cairo University
city: Mansoura
country: Egypt
facility: Mansoura University Children's Hospital
city: Jeddah
country: Saudi Arabia
facility: King Abdulaziz University Hospital
state: Western Region
city: Abha
country: Saudi Arabia
facility: Asser Central Hospital
city: Riyadh
country: Saudi Arabia
facility: King Khalid University Hospital
city: Tunis
country: Tunisia
facility: National Center for Bone Marrow Transplantation
state: Bad Saadoun
city: Sousse
country: Tunisia
facility: Farhat Hached Hospital, Hematology Department
city: Tunis
country: Tunisia
facility: Principal Military Hospital of Instruction of Tunis
city: Adana
country: Turkey
facility: Cukurova University
city: Ankara
country: Turkey
facility: Hacettepe University
city: Istanbul
country: Turkey
facility: Istanbul University
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: London
country: United Kingdom
facility: Barts and The London
city: London
country: United Kingdom
facility: Evelina Children's Hospital
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Janet Kwiatkowski, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kwiatkowski 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.