E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
transfusiondependent β-thalassaemia |
|
E.1.1.1 | Medical condition in easily understood language |
Transfusion-dependent Thalassemia |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 22.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10081911 |
E.1.2 | Term | Transfusion dependent thalassaemia |
E.1.2 | System Organ Class | 100000004850 |
|
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 |
The primary objective of this study is to evaluate the efficacy of 3 multiple doses of VIT-2763: 60 mg once daily (QD), 60 mg twice daily (BID) and 120 mg BID versus placebo, as measured by reduction in RBC transfusion burden from Week 13 to Week 24 of treatment, to identify the most efficacious and safe dose |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives are to evaluate the effects of VIT-2763 on the following measures: * To evaluate the reduction in number of RBC transfusions (units) over Weeks 13 to 24. * To evaluate the proportion of subjects showing 50% RBC transfusion burden reduction assessed over any consecutive 12-week interval during the treatment period of 24 weeks. * To evaluate the proportion of subjects showing 33% RBC transfusion burden reduction assessed over any consecutive 12-week interval during the treatment period of 24 weeks. * To evaluate mean change from baseline in symptoms and quality of life (QoL). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Body weight ≥40.0 kg and ≤100 kg at screening • Documented diagnosis of beta-thalassaemia or Hb E/beta-thalassaemia • Red blood cell (RBC) transfusion dependence, defined as at least 6 RBC units in the 24 weeks prior to randomisation and no transfusion-free period for ≥35 days during that period • Ability to understand the requirements of the study and provide written informed consent |
|
E.4 | Principal exclusion criteria |
• Documented diagnosis of Hb S/beta-thalassaemia, alfa-thalassaemia, or delta beta (δβ)- thalassaemia, or hereditary persistence of foetal Hb. • History of partial or total splenectomy within 4 months prior to screening. • History of myocardial iron overload • Chronic liver disease or history of liver cirrhosis • Clinically relevant renal disease • History or clinically important finding of cardiac disorders • History of clinically significant lung disease • Uncontrolled hypertension (> Grade 1 according to NCI CTCAE current version) • Unable to take and absorb oral medications. • Pregnancy or breastfeeding • History of drug or alcohol abuse within 2 years prior to screening • History or concomitant solid tumours and/or haematological malignancies unless resolved in the ≥5 past years. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects experiencing ≥33% reduction of RBC units from baseline and a reduction of ≥2 units assessed consecutively from Week 13 to Week 24, compared to the baseline transfusion burden during the last 12 weeks prior to randomisation for VIT-2763 versus placebo. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 13 to Week 24 comparing to Baseline (Day -83 to Day 1) |
|
E.5.2 | Secondary end point(s) |
- Change from baseline in RBC transfusions over Weeks 13 to 24 compared to the baseline RBC transfusion burden derived using the last 12 weeks prior to randomization. [Time Frame: Week 13 to Week 24 comparing to Baseline (Day -83 to Day 1)] - Proportion of patients achieving ≥50% reduction of RBC transfusions and ≥2 units assessed over any consecutive 12- week interval from Week 1 to 24. [Time Frame: Any consecutive 12-week interval from Week 1 to Week 24 comparing to Baseline (Day -83 to Day 1)] - Proportion of patients achieving ≥33% reduction of RBC transfusions and ≥2 units assessed over any consecutive 12-week interval from Week 1 to 24. [Time Frame: Any consecutive 12-week interval from Week 1 to Week 24 comparing to Baseline (Day -83 to Day 1)] - Mean change from baseline in Quality of Life (QoL) total score Transfusion-dependent QoL Questionnaire (TranQuol): a disease-specific, validated, QoL measure developed for thalassaemia patients. The adult version includes 36 questions grouped into 5 domains: physical health, emotional health, sexual health, family functioning, and school/career functioning. The total score ranges from 0 (worst) to 100 (best). [Time Frame: Week 15 and Week 24 comparing to Baseline (Day 1)] |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Change from baseline in RBC transfusions over Weeks 13 to 24 compared to the baseline RBC transfusion burden Week 13 to Week 24 comparing to Baseline (Day -83 to Day 1)
- Proportion of patients achieving ≥50% reduction of RBC transfusions Any consecutive 12-week interval from Week 1 to Week 24 comparing to Baseline (Day -83 to Day 1)
- Proportion of patients achieving ≥33% reduction of RBC transfusions Any consecutive 12-week interval from Week 1 to Week 24 comparing to Baseline (Day -83 to Day 1)
- Mean change from baseline in Quality of Life (QoL) total score Transfusion-dependent QoL Questionnaire (TranQuol) Week 15 and Week 24 comparing to Baseline (Day 1) |
|
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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
Bulgaria |
Egypt |
Greece |
Israel |
Italy |
Lebanon |
Malaysia |
Thailand |
Turkey |
United Kingdom |
United States |
|
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
|
The end of the study is defined as the date of the last visit of the last subject in the study or last scheduled procedure shown in Table 1 of the study Protocol for the last subject |
|
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 | 1 |
E.8.9.1 | In the Member State concerned days | 17 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 26 |