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

NCT ID: NCT02041299

Last Updated: 2021-08-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 230 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-17
• Study Completion Date: 2019-06-18

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.

Conditions

Iron Overload; Sickle Cell Disease; Other Anemias

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Deferiprone

Intervention Type: DRUG

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.

Group Type: ACTIVE_COMPARATOR

Deferoxamine

Intervention Type: DRUG

Interventions

Deferiprone

Intervention Type: DRUG

Deferoxamine

Intervention Type: DRUG

Other Intervention Names

Ferriprox tablets; Deferiprone oral solution

Eligibility Criteria

Inclusion Criteria

1. Male or female ≥ 2 years of age;

Exclusion Criteria

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

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

• Minimum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ApoPharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janet Kwiatkowski, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

Children's Hospital Oakland

Oakland, California, United States

University of Illinois at Chicago

Chicago, Illinois, United States

Children's Hospital

New Orleans, Louisiana, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Children's Hospital of Michigan

Detroit, Michigan, United States

The Children's Hospital of Philadephia

Philadelphia, Pennsylvania, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Centro Infantil Boldrini

Campinas, , Brazil

Hospital de Clínicas de Porto Alegre-HCPA,

Rio Branco, , Brazil

Instituto Estadual de Hematologia Arthur Siqueira Cavalcanti - HEMORIO

Rio de Janeiro, , Brazil

Casa de Saúde Santa Marcelina

São Paulo, , Brazil

Universidade Federal de São Paulo

São Paulo, , Brazil

Hospital for Sick Kids

Toronto, Ontario, Canada

Mansoura University Children's Hospital

Al Mansurah, , Egypt

Alexandria University

Alexandria, , Egypt

Zagazig University

Alexandria, , Egypt

Ains Shams University

Cairo, , Egypt

Cairo University

Cairo, , Egypt

Pediatric Hospital of Cairo University

Cairo, , Egypt

King Abdulaziz University Hospital

Jeddah, Western Region, Saudi Arabia

Asser Central Hospital

Abhā, , Saudi Arabia

King Khalid University Hospital

Riyadh, , Saudi Arabia

National Center for Bone Marrow Transplantation

Tunis, Bad Saadoun, Tunisia

Farhat Hached Hospital, Hematology Department

Sousse, , Tunisia

Principal Military Hospital of Instruction of Tunis

Tunis, , Tunisia

Cukurova University

Adana, , Turkey (Türkiye)

Hacettepe University

Ankara, , Turkey (Türkiye)

Istanbul University

Istanbul, , Turkey (Türkiye)

Hammersmith Hospital

London, , United Kingdom

Barts and The London

London, , United Kingdom

Evelina Children's Hospital

London, , United Kingdom

Imperial College Healthcare NHS Trust

London, , United Kingdom

Countries

United States; Brazil; Canada; Egypt; Saudi Arabia; Tunisia; Turkey (Türkiye); United Kingdom

References

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.

Reference Type: DERIVED

PMID: 34847228 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

LA38-0411

Identifier Type: -

Identifier Source: org_study_id