| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with transfusional iron overload due to hereditary anemias such as sickle cell disease, β-thalassemia and Diamond-Blackfan anemia; acquired anemias such as Myelodysplastic Syndrome and other forms of bone marrow failure. |
|
| MedDRA Classification |
| 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 safety and tolerability based on clinical assessments of two doses of FBS0701 when administered daily to patients with transfusional iron overload To identify a differential response between dose groups in liver iron content determined by magnetic resonance imaging (MRI). |
|
| E.2.2 | Secondary objectives of the trial | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| 1. Willing and able to sign the approved informed consent. 2. Age: 18-60 years old at Screening 3. Transfusional iron overload due to: hereditary anemias such as sickle cell disease, β-thalassemia and Diamond-Blackfan anemia; acquired anemias such as Myelodysplastic Syndrome and other forms of bone marrow failure. Patients must also: a. Be transfusion-dependent (8 or more transfusions annually) and b. Require chronic treatment with deferoxamine, deferasirox, and/or deferiprone. 4. Willing to discontinue all existing iron chelation therapies for a minimum period of two to five days prior to first dose of FBS0701, the 24 week duration of the study and 1 week after last dose for a total of approximately 26 weeks. 5. Serum ferritin > 500 ng/mL at Screening. 6. Baseline (Day -14 to Day -7) liver iron concentration (LIC) between ≥3.5 and <30 mg iron per g (equivalent dry weight, liver) determined by FerriScan MRI. 7. Baseline (Day -14 to Day -7) cardiac MRI T2* ≥10 milliseconds. 8. Mean of the previous three pre-transfusion hemoglobin concentrations ≥ 7.5 g/dL. 9. Agrees to use an approved method of contraception from Screening and until 28 days after the last administration of the study drug. Agreed methods of contraception may include: condom; use of birth control pills, patches, implants or injections, diaphragm with vaginal spermicide, intrauterine device (IUD) and/or surgical sterilization (vasectomy or tubal ligation at least six months prior to dosing). Patients practicing abstinence must agree to use an approved method of contraception should they become sexually active during the study. A monthly pregnancy test will be performed on all female patients of child-bearing potential during the Screening and study period. |
|
| E.4 | Principal exclusion criteria |
| 1.As a result of medical review, physical examination or Screening investigations, the Principal Investigator considers the patient unfit for the study. 2.Non-elective hospitalization within the 30 days prior to Baseline testing. (Patients with sickle cell anemia who are admitted to the hospital for management of sickle crisis pain whose uncomplicated hospital course was four days or less and who, 14 days prior to Baseline testing, have returned to their previous health status are acceptable.) 3.Evidence of clinically relevant oral, cardiovascular, gastrointestinal, hepatic, renal, endocrine, pulmonary, neurologic, psychiatric, immunologic, bone marrow or skin disorder as determined by the Investigator. 4.Evidence of significant renal insufficiency; e.g., serum creatinine above the upper limit of normal, proteinuria greater than 2 gm per day or calculated creatinine clearance of less than 60 mL/minute. 5.Cardiac left ventricular ejection fraction: a.Outside the locally determined normal range in the 12 months prior to Screening by echocardiography or MRI and b.<55% at Baseline testing by MRI 6.Known sensitivity to magnesium stearate, croscarmellose sodium or FBS0701 7.Platelet count below 150,000/�L and/or absolute neutrophil count less than 1500/mm3 at Screening 8.Alkaline phosphatase, AST or ALT a.>5 times the local upper limit of normal at any time in the previous 12 months or b.>3 times the upper limit of normal at Screening 9.Use of any investigational agent within the 30 days prior to the Baseline testing. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Safety and Tolerability: Demographics will be tabulated and summarized. Medical and surgical history data at Screening will be listed, as will Physical Examination data including height and weight, vital signs (resting heart rate, semi-supine systolic/diastolic blood pressure, respiratory rate and temperature), and ECG parameters will be tabulated and summarized. Treatment-emergent adverse events will be listed and summarized per treatment. All adverse events reported in this study will be coded using MedDRA (Medical Dictionary for Regulatory Activities). Laboratory values outside the laboratory normal ranges will be listed separately with comments as to their clinical significance. All patients who have taken at least one dose will be included in the safety analysis consistent with an intention-to-treat analysis. Pharmacodynamics: Changes in Liver Iron Concentration (LIC) as assessed by FerriScan magnetic resonance imaging (MRI) from Baseline to Week 12 and Week 24 will be calculated and summarized by treatment arm. Changes in LIC assessed by FerriScan MRI normalized for initial LIC from Baseline to Week 12 and 24 will be calculated and summarized by treatment arm. Changes in LIC assessed by FerriScan MRI from Baseline to Week 12 and 24 normalized for iron intake by blood transfusion over the course of the study will be calculated and summarized by treatment arm. Total liver volume and total hepatic iron content as assessed by MRI at Baseline, Week 12 and Week 24 will be calculated and summarized by treatment arm. |
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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 | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| 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 | Yes |
| E.8.2.3.1 | Comparator description |
| - same IMP used at different dosage |
|
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 5 |
| 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 | Information not present in EudraCT |
| 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 |
|
| 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
|
| La data di fine sperimentazione e` stabilita come come la data di chiusura del database |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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