E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Iron overload in sickle cell disease or other anemias |
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E.1.1.1 | Medical condition in easily understood language |
Iron overload in sickle cell disease or other anemias |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10005329 |
E.1.2 | Term | Blood and lymphatic system disorders |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the long-term safety and tolerability of deferiprone in iron-overloaded patients with sickle cell disease or other anemias |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of deferiprone in the treatment of iron overload in patients with sickle cell disease or other anemias who have received deferiprone for up to 3 years |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Completed study LA38-0411. |
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E.4 | Principal 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 ≥ 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety:
• Adverse events (AEs): Frequency, severity, time to onset, duration, and relatedness to study product
• Serious adverse events (SAEs): Frequency, severity, time to onset, duration, and relatedness to study product
• Number of discontinuations due to AEs
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
• Hematology: Group 1: Monthly up to Visit 9 (End of Study) or the Early Termination visit; Group 2: Weekly up to Visit 3 (Week 26), then biweekly up to Visit 5 (Week 52), then monthly up to Visit 9 (End of Study) or the Early Termination visit
• Biochemistry: Visit 1 and semi-annually up to Visit 9 or the Early Termination visit
• Serology: Visits 1 and 9
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E.5.2 | Secondary end point(s) |
Efficacy:
For Group 1, the change from baseline to Year 1 is derived from study LA38-0411. For Group 2, there is no Year 3 of deferiprone treatment.
• The change from baseline to Year 1 (both groups; Group 1 data are from LA38-0411), from baseline to Year 2 (both groups), and from baseline to Year 3 (Group 1 only) in liver iron concentration (LIC), as measured by magnetic resonance imaging (MRI)
• The change from baseline to Year 1 (both groups; Group 1 data are from LA38-0411), from baseline to Year 2 (both groups), and (Group 1 only) from baseline to Year 3 in cardiac MRI T2*
• The change from baseline to Year 1 (both groups; Group 1 data are from LA38-0411 data), from baseline to Year 2 (both groups), and from baseline to Year 3 (Group 1 only) in serum ferritin
• Responder analysis, defined as 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* at Year 1 (both groups; Group 1 data are from LA38-0411), at Year 2 (both groups), and at Year 3 (Group 1 only)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Serum ferritin: Visit 1 and quarterly up to Visit 9 or the Early Termination visit
• Liver MRI scan: Annually, at Visits 1, 5, and 9 or Early Termination visit
• Cardiac MRI T2* scan: Annually, at Visits 1, 5, and 9 or Early Termination visit
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Egypt |
Saudi Arabia |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |