| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Transfusion-dependent Thalassemia, Non-transfusion-dependent Thalassemia |
|
| E.1.1.1 | Medical condition in easily understood language |
| Transfusion-dependent Thalassemia, Non-transfusion-dependent Thalassemia |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| Percentage of patient claimed preference of deferasirox FCT over deferasirox DT as measured by preference questionnaire at Week 48 |
|
| E.2.2 | Secondary objectives of the trial |
•Percentage of patient claimed preference of deferasirox FCT, deferasirox DT, and previous iron chelation as measured by preference questionnaire at Week 28.
•Percentage of patient claimed preference of deferasirox DT, over previous iron chelation as measured by preference questionnaire at Week 4 and Week 24.
•Percentage of preference reasons for deferasirox FCT over deferasirox DT as measured by preference questionnaire at Week 28 and Week 48.
•To evaluate the effect of deferasirox FCT compared with deferasirox DT on patient compliance using pill count at hospital level. Relative consumed pill count during deferasirox FCT (Week 25 to 48) compared with deferasirox DT (Baseline day 1 to 24).
•Change in scores on patient palatability using Palatability questionnaire which evaluates taste and aftertaste. Changes will be performed for both formulations (DT/FCT) for the overall score at Week 4, Week 24, Week 28 and Week 48 and overall score at Screening for iron chelators. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Prior to any screening procedures are performed, written informed consent/assent must be provided. For pediatric patients, consent will be obtained from parent(s) or legal patient's representative. Investigators will also obtain assent of patients according to local, regional or national guidelines.
2. Male and female patient aged ≥ 2 years
3. Exjade naïve patient or chelated naive patient or treated by other chelators for at least 6 months, such as: a. Deferiprone/ DFP b. Deferoxamine /DFO c. Combination (DFO + DFP)
4. Subject is willing to discontinue current iron chelation therapy at least 7 days prior to the first day and for the duration of the study
5. Patients with transfusion-dependent thalassemia (independent of underlying condition) with transfusional iron overload as shown by: -a serum ferritin level of > 1000 ng/ml at screening and if available, LIC > 3 mg Fe/g dw until 6 months prior to screening
6. Patients with non-transfusion-dependent thalassemia with iron overload as shown by: -a serum ferritin level of ≥ 800 ng/ml at screening and if available, LIC ≥ 5 mg Fe/g dw until 6 months prior to screening |
|
| E.4 | Principal exclusion criteria |
1. Male and female patient aged < 2 years
2 Written consent/assent from patients/parents/legal representative is not obtained
3 Creatinine clearance below the contraindication limit in the locally approved prescribing information.
4 Serum creatinine level > 1.5 x ULN (upper limit of normal)
5 AST (SGOT) /ALT (SGPT) > 5 x ULN, unless if LIC confirmed as <10 mg Fe/dw within 6 months prior to screening visit.
6 Significant proteinuria as indicated by a urinary protein/creatinine ratio > 0.5 mg/mg in a non-first void urine sample.
7 Patients with significant impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral deferasirox (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
8 Clinical or laboratory evidence of active Hepatitis B or Hepatitis C (HBsAg in the absence of HBsAb OR HCV Ab positive with HCV RNA positive).
9 Patients with psychiatric or addictive disorders which prevent them from giving their informed consent or undergoing any of the treatment options or patients unwilling or unable to comply with the protocol (including use of electronic devices for ePRO).
10 Patients with a known history of HIV seropositivity (Elisa or Western blot).
11 History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.
12 Patients participating in another clinical trial or receiving an investigational drug.
13 History of hypersensitivity to any of the study drug or excipients.
14 Significant medical condition interfering with the ability to partake in this study (e.g. systemic uncontrolled hypertension, unstable cardiac disease not controlled by standard medical therapy, systemic disease (cardiovascular, renal, hepatic, etc.).
15 Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment
16 Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
17 Sexually active males unless they use a condom during intercourse while taking drug and for 28 days after stopping study medication and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Percentage of patient preference for deferasirox FCT vs deferasirox DT at Week 48 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
•Percentage of patient preference for deferasirox FCT vs deferasirox DT vs previous previous iron chelation at week 28
•Percentage of patient preference for deferasirox DT vs previous iron chelation at week 4 and 24
•Percentage of reasons for preference of deferasirox FCT vs. deferasirox DT at week 28 and 48
•Pill counts to assess drug compliance for deferasirox DT vs FCT
•Change in scores of patients palatability preference at week 4, 24, 28 and 48
•Percentage of patients satisfaction in regards to the drug intake for deferasirox DT vs FCT at screening, week 4, 24, 28 and 48
•Assess efficacy of deferasirox DT vs DCT by analysis of serum ferritin levels |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
•Week 28
•Week 4 and Week 24
•Week 28 and Week 48
•Baseline to week 24, Week 25 to 48
•Screening, week 4, 24, 28 and 48
•Screening, week 4, 24, 28 and 48
•Baseline, every 4 weeks up to 48 weeks |
|
| 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 | No |
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
| Patient/observer reported outcomes (preference, satisfaction, GI symptoms and palatability) |
|
| 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 | No |
| E.8.1.1 | Randomised | No |
| 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 | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| 1 arm (patients receive Deferasirox DT, then transition to FCT) |
|
| 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.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
Will this trial be conducted at a single site globally?
| No |
| E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
| E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
| Algeria |
| Egypt |
| Iran, Islamic Republic of |
| Lebanon |
| Morocco |
| Saudi Arabia |
| Thailand |
| Turkey |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
The end of study is defined as the earliest occurrence of one of the following:
- The patient has reached Visit number 27 –Week 96 at Extension phase.
- Deferasirox FCT is locally reimbursed for this indication (only applicable in Extension phase)
- Another clinical study becomes available that can continue to provide deferasirox FCT in this patient population and all patients ongoing are eligible to be transferred to that clinical study. |
|
| E.8.9 Initial estimate of the duration of the trial |
| 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 | 10 |
Print
