Long-term Safety and Efficacy of Ferriprox® in Iron Overloaded Patients With Sickle Cell Disease or Other Anemias

Study Overview
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Brief Summary
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This is a long-term follow-up to an earlier study, LA38-0411. Its purpose is to gather more information about the safety and efficacy of deferiprone in patients with sickle cell disease or other anemias who suffer from iron overload caused by regular blood transfusions.

Detailed Description
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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 long-term efficacy, safety, and tolerability of deferiprone to treat iron overload in patients who have sickle cell disease or other anemias. Only patients who have completed an earlier study, LA38-0411, are eligible to enroll in this one.

Official Title
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Long-term Safety and Efficacy Study of Ferriprox® for the Treatment of Transfusional Iron Overload in Patients With Sickle Cell Disease or Other Anemias

Conditions
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Iron Overload, Sickle Cell Disease, Other Anemias

Intervention / Treatment
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* Drug: Deferiprone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completed study LA38-0411 Females of childbearing potential must have a negative pregnancy test result at Visit 1. In addition, if applicable, they must: Use an effective method of contraception according to local requirements, during the study and within 30 days following their last dose of study medication, OR Have had a tubal ligation (supporting evidence required), OR Have had a hysterectomy (supporting evidence required), OR Participate in a non-heterosexual lifestyle, OR Have a male sexual partner who has been sterilized (supporting evidence required) Fertile heterosexual males and/or their partners must agree to use an effective method of contraception during the study and for 30 days following the last dose of study medication All patients and/or their authorized legal representatives must provide signed and dated written informed consent prior to the first study intervention, and assent will be obtained from patients who are considered to be minors. Patients must be able to adhere to study restrictions, appointments, and evaluation schedules. Exclusion Criteria: Plan to participate in another clinical trial at any time from the day of enrollment until 30 days post-treatment in the current study For only those patients who were treated with deferoxamine in study LA38-0411 (Group 2): Presence of any medical condition (including clinically significant laboratory abnormalities, such as ALT ≥ 5 x ULN or creatinine ≥ 2 x ULN), psychological condition, or psychiatric condition which in the opinion of the investigator would cause participation in the study to be unwise. Pregnant, breastfeeding, or planning to become pregnant during the study period. Treatment failure after 1 year on deferiprone which in the investigator's judgment indicates the need for the patient to be started on a different iron chelator

Ages Eligible for Study
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Minimum Age: 3 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Deferiprone 3 years<br>Patients in this group are those who were randomized to the deferiprone arm in study LA38-0411, and hence will receive deferiprone for a total of 3 years (1 year in the initial study plus 2 years in the extension study).. | Drug: Deferiprone<br> <br> * Other names: Deferiprone oral solution;|
| Experimental: Group 2: Deferiprone 2 years<br>Patients in this group are those who were randomized to the deferoxamine arm in study LA38-0411, and hence will receive deferiprone for 2 years (both of them in the extension study). | Drug: Deferiprone<br> <br> * Other names: Deferiprone oral solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events (AEs) | Number of participants in each group with AEs, by frequency, severity, time to onset, duration, and relatedness to study product | From the first day of the study until the last study visit (Week 104 or early termination) | 
| Number of subjects with serious adverse events (SAEs) | Number of participants in each group with SAEs, by frequency, severity, time to onset, duration, and relatedness to study product | From the first day of the study until 30 days after the last dose | 
| Discontinuations due to adverse events | Number of participants discontinued from the study because of adverse events | From the first day of the study until Week 104 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to end of study in liver iron concentration (LIC) | LIC will be determined by MRI | Group 1: From Week 0 of study LA38-0411 until the last visit of study LA38-EXT (Week 104 or early termination). Group 2: From Week 0 of study LA38-EXT until the last visit (Week 104 or early termination). | 
| Change from baseline to end of study in cardiac MRI T2* | Myocardial MRI T2* will be used to monitor the myocardial iron load resulting from chronic transfusions. Low T2* levels reflect a high cardiac iron concentration and high T2* values reflect low cardiac iron. | Group 1: From Week 0 of study LA38-0411 until the last visit of study LA38-EXT (Week 104 or early termination). Group 2: From Week 0 of study LA38-EXT until the last visit (Week 104 or early termination). | 
| Change from baseline to end of study in serum ferritin |  | Group 1: From Week 0 of study LA38-0411 until the last visit of study LA38-EXT (Week 104 or early termination). Group 2: From Week 0 of study LA38-EXT until the last visit (Week 104 or early termination). | 
| Responder analysis | The percentage of patients who show a ≥20% decline from baseline in LIC or serum ferritin or a ≥20% increase from baseline in cardiac MRI T2* | Group 1: From Week 0 of study LA38-0411 to Weeks 0, 52, and 104 of LA38-EXT (1, 2, and 3 years of deferiprone treatment, respectively). Group 2: From Week 0 of study LA38-EXT to Weeks 52 and 104 (1 and 2 years of deferiprone treatment, respectively). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Deferiprone, Iron overload, Sickle cell disease, Ferriprox, Iron chelation