Iron Overload, Other Anemias, Sickle Cell Disease
Conditions
Keywords
Iron overload, Sickle cell disease, Deferiprone, Ferriprox, Iron chelation
Brief summary
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
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.
Interventions
DRUGDeferiprone
Sponsors
ApoPharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Completed study LA38-0411 2. 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) 3. 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 4. 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
1. Plan to participate in another clinical trial at any time from the day of enrollment until 30 days post-treatment in the current study 2. 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 (alanine aminotransferase) ≥ 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. 3. Pregnant, breastfeeding, or planning to become pregnant during the study period. 4. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Adverse Events | From the first day of the study until the last study visit (Week 104 or early termination) | Number of patients with at least one adverse event (AE) of any type; number of patients with at least one serious adverse event, and number of patients who withdrew from the study due to an AE |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Liver Iron Concentration (LIC) | One year, two years, and three years after the start of deferiprone therapy | LIC was measured by MRI, in units of mg of iron per gram of liver (dry weight). The change from baseline in LIC was determined for three different periods of exposure to deferiprone: one year, two years, and three years. |
| Change From Baseline in Cardiac MRI T2* | One year, two years, and three years after the start of deferiprone therapy | The change from baseline in cardiac MRI T2\* was determined for three different periods of exposure to deferiprone: one year, two years, and three years |
| Change From Baseline in Serum Ferritin | One year, two years, and three years after the start of deferiprone therapy | The change from baseline in serum ferritin (SF) was determined for three different periods of exposure to deferiprone: one year, two years, and three years. |
Countries
Canada, Egypt, Saudi Arabia, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Deferiprone All patients in this study received deferiprone | 134 |
| Total | 134 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Physician Decision | 3 | 0 |
| Overall Study | Pregnancy | 1 | 1 |
| Overall Study | Protocol Violation | 8 | 1 |
| Overall Study | Termination of study | 20 | 11 |
| Overall Study | Withdrawal by Subject | 6 | 3 |
Baseline characteristics
| Characteristic | Deferiprone |
|---|---|
| Age, Continuous | 16.2 years STANDARD_DEVIATION 8.6 |
| Cardiac iron at baseline | 32.69 milliseconds STANDARD_DEVIATION 17.66 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 133 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Liver iron concentration at baseline | 14.93 mg iron per gram of liver dry weight STANDARD_DEVIATION 7.61 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 114 Participants |
| Region of Enrollment Canada | 2 participants |
| Region of Enrollment Egypt | 109 participants |
| Region of Enrollment Saudi Arabia | 5 participants |
| Region of Enrollment United Kingdom | 4 participants |
| Region of Enrollment United States | 14 participants |
| Serum ferritin level at baseline | 3894 micrograms per liter STANDARD_DEVIATION 2591 |
| Sex: Female, Male Female | 53 Participants |
| Sex: Female, Male Male | 81 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 134 |
| other Total, other adverse events | 99 / 134 |
| serious Total, serious adverse events | 35 / 134 |
Outcome results
Primary
Number of Patients With Adverse Events
Number of patients with at least one adverse event (AE) of any type; number of patients with at least one serious adverse event, and number of patients who withdrew from the study due to an AE
Time frame: From the first day of the study until the last study visit (Week 104 or early termination)
Population: Safety population (all enrolled patients who took at least one dose of study drug)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Deferiprone | Number of Patients With Adverse Events | Number of patients with any type of adverse event | 104 Participants |
| Deferiprone | Number of Patients With Adverse Events | Number of patients with a serious adverse event | 35 Participants |
| Deferiprone | Number of Patients With Adverse Events | Number of patients who discontinued due to an AE | 2 Participants |
Secondary
Change From Baseline in Cardiac MRI T2*
The change from baseline in cardiac MRI T2\* was determined for three different periods of exposure to deferiprone: one year, two years, and three years
Time frame: One year, two years, and three years after the start of deferiprone therapy
Population: ITT population. Cardiac MRI T2\* data for one year of exposure to deferiprone were obtained from 121 patients, data for two years from 110 patients, and data for three years from 58 patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Deferiprone | Change From Baseline in Cardiac MRI T2* | Change from baseline in cardiac iron after 1 year | 1.02 milliseconds | Standard Deviation 19.65 |
| Deferiprone | Change From Baseline in Cardiac MRI T2* | Change from baseline in cardiac iron after 2 years | 1.00 milliseconds | Standard Deviation 21.18 |
| Deferiprone | Change From Baseline in Cardiac MRI T2* | Change from baseline in cardiac iron after 3 years | 0.98 milliseconds | Standard Deviation 24.53 |
Comparison: Change from baseline after 1 year of deferiprone therapyp-value: 0.3146t-test, 2 sided
Comparison: Change from baseline after 2 years of deferiprone therapyp-value: 0.9454t-test, 2 sided
Comparison: Change from baseline after 3 years of deferiprone therapyp-value: 0.4336t-test, 2 sided
Secondary
Change From Baseline in Liver Iron Concentration (LIC)
LIC was measured by MRI, in units of mg of iron per gram of liver (dry weight). The change from baseline in LIC was determined for three different periods of exposure to deferiprone: one year, two years, and three years.
Time frame: One year, two years, and three years after the start of deferiprone therapy
Population: Intent-to-Treat (ITT) population (patients who received at least one dose of study drug and had a baseline and at least one post-baseline efficacy assessment). LIC data for one year of exposure to deferiprone were obtained from 129 patients, data for two years from 112 patients, and data for three years from 59 patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Deferiprone | Change From Baseline in Liver Iron Concentration (LIC) | Change from baseline in LIC after 1 year | -2.64 mg of iron per gram of liver dry weight | Standard Deviation 4.64 |
| Deferiprone | Change From Baseline in Liver Iron Concentration (LIC) | Change from baseline in LIC after 2 years | -3.91 mg of iron per gram of liver dry weight | Standard Deviation 6.38 |
| Deferiprone | Change From Baseline in Liver Iron Concentration (LIC) | Change from baseline in LIC after 3 years | -6.64 mg of iron per gram of liver dry weight | Standard Deviation 7.72 |
Comparison: Change from baseline after 1 year of deferiprone therapyp-value: 0t-test, 2 sided
Comparison: Change from baseline after 2 years of deferiprone therapyp-value: 0t-test, 2 sided
Comparison: Change from baseline after 3 years of deferiprone therapyp-value: 0t-test, 2 sided
Secondary
Change From Baseline in Serum Ferritin
The change from baseline in serum ferritin (SF) was determined for three different periods of exposure to deferiprone: one year, two years, and three years.
Time frame: One year, two years, and three years after the start of deferiprone therapy
Population: ITT population. Serum ferritin data for one year of exposure to deferiprone were obtained from 125 patients, data for two years from 96 patients, and data for three years from 55 patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Deferiprone | Change From Baseline in Serum Ferritin | Change from baseline in SF after 1 year | -1 micrograms per liter | Standard Deviation 1986 |
| Deferiprone | Change From Baseline in Serum Ferritin | Change from baseline in SF after 2 years | -771 micrograms per liter | Standard Deviation 2171 |
| Deferiprone | Change From Baseline in Serum Ferritin | Change from baseline in SF after 3 years | -1016 micrograms per liter | Standard Deviation 3617 |
Comparison: Change from baseline after 1 year of deferiprone therapyp-value: 0.9952t-test, 2 sided
Comparison: Change from baseline after 2 years of deferiprone therapyp-value: 0.0008t-test, 2 sided
Comparison: Change from baseline after 3 years of deferiprone therapyp-value: 0.042t-test, 2 sided