E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054658 |
E.1.2 | Term | Thalassemia |
E.1.2 | System Organ Class | 100000004850 |
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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 |
To assess the effect of INC424 on transfusion requirement |
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E.2.2 | Secondary objectives of the trial |
Key secondary:
- to assess the effect of INC424 on spleen volume
Other secondary:
- to assess the effect of INC424 on pre transfusion hemoglobin levels
- to assess the effect of INC424 ib spleen lenght
- to assess pharmacokinetics of INC424
- to assess the safety of INC424 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients 18 years of age or older
2. Patients with thalassemia on a regular and stable transfusion regimen (at least 2 RBC units within every 4-week interval for 24 weeks prior to Screening) and anticipated to receive the same transfusion regimen during the study.
3. Patients with spleen enlargement at Screening, defined as
a. Spleen palpable below the costal margin, AND
b. Spleen volume of ≥ 450 cm3 as confirmed by MRI (or CT scan in applicable patients)
4. Patients need to be on iron chelation treatment (deferoxamine or deferasirox) for at least four weeks prior to Screening. |
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E.4 | Principal exclusion criteria |
1. Splenectomy prior to or planned during the study
2. Active serious bacterial, mycobacterial, fungal, parasitic or viral infection which requires therapy (e.g., pneumonia, tuberculosis, systemic mycosis, herpes zoster)
3. Hemoglobin <65 g/L (<4.0 mmol/L) at Screening
4. Platelet count < 75 109/L, absolute neutrophils count < 1.5 109/L at Screening
5. Estimated MDRD < 30 mL/min/1.73 m2 at Screening
6. ALT (SGPT) levels >5 times ULN at Screening
7. Hepatocellular disease such as hepatitis B (presence of HBs antigen), hepatitis C (presence of HCV RNA), liver cirrhosis
8. HIV positivity |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent change of RBC (Red Blood Cell) transfusion requirement between week 6 and week 30 compared to the baseline period between week -24 and the day before first study drug administration |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
week -24 to baseline period against week 6 to week 30 |
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E.5.2 | Secondary end point(s) |
Key secondary:
- change of spleen volume from baseline measured by MRI or CT at week 12 and week 30
Other secondary:
- change of pre-transfusion hemoglobin level from baseline at each post-baseline visit
- change of spleen length from baseline over time measured by palpation
- pharmacokinetic (PK) parameters of Cmin and Cmax (1h) of INC424 by actual dose administered
- number of participants with adverse events as measure of satefy and tolerability (adverse events, serious adverse events, lab results, ECGs, vital signs) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
for Key secondary:
- baseline, week 12 and week 30
for Other secondary:
- baseline; week 1, 2, 3, 4, 6, 12, 18, 24, 30
- baseline; week 1, 2, 3, 4, 6, 12, 18, 24, 30
- baseline, week 2 and week 12
- baseline; week 1, 2, 3, 4, 6, 12, 18, 24, 30 |
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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 | Yes |
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 |
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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 | 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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 1 |
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 | 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 |
Greece |
Italy |
Lebanon |
Thailand |
Turkey |
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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
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Last Patient Last Visit defined as all patients have completed the last assessment (= safety follow-up/study completion visit 35 +/- 5 days after their last dose of study drug) |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |