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 |
An inherited blood disorder where red blood cells become sickle/crescent shaped. These sickle cells can block blood flow, and result in pain and organ damage. |
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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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10040644 |
E.1.2 | Term | Sickle cell disease |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic 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 |
The primary objective of this study is to explore the effect of VIT-2763 on markers of haemolysis. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to assess the safety and tolerability of VIT-2763 in SCD patients. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject has provided the appropriate written informed consent before any study-specific procedures are performed including screening procedures. 2. Ability to understand the requirements of the study and abide by the study restrictions, and agreement to return for the required assessments. 3. Male or female subjects with confirmed diagnosis of SCD, including only HbS/S or HbS/βT0 genotype. 4. Subjects who had at least 1 and no more than 10 VOC episodes reported within 12 months prior to screening. Note: A VOC episode is defined as a documented episode of acute chest syndrome or acute painful crisis for the main indication of SCD, which led to health-professional instructed prescription or use of opioids (excluding codeine) for moderate to severe pain. 5. 18 to 60 years of age inclusive at the time of screening. 6. Body weight ≥40 kg and ≤120 kg at screening and baseline. 7. Absolute reticulocyte count or and percentage reticulocyte count >1.5 × ULN during screening. 8. Subjects on concomitant hydroxyurea must be on a stable dose (mg/kg) for ≥3 months prior to screening Visit V1. There should be no planned dose adjustments during the course of the study in the opinion of the Investigator. 9. Female subjects of childbearing potential, must have negative pregnancy tests at screening (serum pregnancy test) and before randomisation (urine pregnancy test), must have stopped breastfeeding as of first dose, and must either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis and source documented) or must be willing to use adequate contraceptive precautions, i.e., highly effective method of birth control. Abstinence should only be used as a contraceptive method if it is in line with the subject´s usual and preferred lifestyle, and periodic abstinence (calendar symptothermal, postovulation methods) is not acceptable method of contraception. Female subjects must agree to use adequate contraception during the study and until at least 1 week after the last dose of IMP or requirements from other co-medications taken, e.g. hydroxyurea or according to local requirements, whichever is longer. Effective contraception (highly effective method of birth control, i.e., with a failure rate of <1% per year, when used consistently and correctly) such as implants, injectables, combined oral contraceptives (see below), intrauterine devices, sexual abstinence, or vasectomised partner must be used. Non-childbearing potential includes being surgically sterilised at least 6 months prior to the study. Note: For female subjects participating in this study, continuous use of hormonal contraception alone is not sufficient, because potential interactions via CYP enzymes may alter the efficacy of hormonal contraception. The continuous use of hormonal contraception by a female subject should be combined with the use of a condom by the male partner; the condom should then be used together with a spermicide or adequate and approved alternatives by the (fertile) male partner.
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E.4 | Principal exclusion criteria |
1. Subjects with confirmed SCD diagnosis other than HbS/S and HbS/βT0. 2. Hb level <6.0 g/dl or >10.4 g/dl for female and >11.0 g/dl for male subjects at screening Visit V1. Note: The Hb value at screening Visit V1 will be used for eligibility determination based on the central laboratory result. However, the baseline Hb value determined at Visit V2 (Day 1 pre-dose) also needs to be within the above specified range, based on the local laboratory result. 3. Having received RBC transfusion therapy within 4 weeks prior to screening, or ongoing or planned RBC transfusion therapy during the course of the study (including chronic, prophylactic, or preventive transfusion to treat SCD). 4. Subject with serum ferritin level <30 µg/l at screening. 5.Calculated TSAT level <25% at screening. However, in case TIBC is within normal ranges of the central laboratory values, the subject will not be excluded. 6. Subjects being hospitalized for SCD-related events (including pain crisis and VOC) within 14 days before the screening visit. Note: SCD must have been the main cause for the hospitalisation to fulfil this criterion. 7. Chronic liver disease or history of liver cirrhosis, and/or alanine aminotransferase or aspartate aminotransferase, above 3-fold the ULN range at baseline. 8. eGFR <45 ml/min/1.73 m2,at screening or on chronic dialysis. Note: eGFR should be estimated according to CKD-EPI formula. 9. Newly diagnosed folate deficiency anaemia (i.e., folic acid <2 ng/ml), which is considered clinically relevant by the Investigator at screening. Subjects with known folate deficiency anaemia who are on ≥12 weeks stable replacement therapy at screening are eligible. 10. Subjects with history of partial or total splenectomy within 3 months prior to the screening visit. 11. Any history or clinically important finding of cardiac or pulmonary disorders, including (but not limited to) clinically relevant or uncontrolled cardiac arrhythmia, cardiomyopathy, coronary disease (unstable angina pectoris or myocardial infarction or elective coronary intervention), valve disorder, or heart failure according to New York Heart Association classification 3-4. 12. A diagnosis of any form of pulmonary hypertension. 13. Any clinically relevant abnormal 12-lead ECG finding during screening or prior to randomisation (as deemed by the Investigator) including (but not limited to) any of the following: - PR interval >0.21 seconds - Evidence or history of second- or third-degree atrioventricular block - QRS interval >0.12 seconds 14. Family history of long-QT syndrome or sudden death without a preceding diagnosis of a condition that could be causative of sudden death (such as known coronary artery disease, congestive heart failure, or terminal cancer) or subjects with QT interval corrected (QTcF) >450 msec. 15. Clinically significant bacterial, fungal, parasitic, or viral infection which requires therapy. Note: Please see the protocol 16. Known history, and/or positive result on screening for hepatitis B surface antigen, hepatitis B virus, hepatitis C virus, or HIV infection. Note: Please see the protocol 17.Known active COVID-19 infection (positive result of a SARS-Cov-2 virus test (nucleic acid or antigen detection) within 2 weeks preceding screening), or any other active infection. Note: Please see the protocol 18. Use of any prohibited medication(s) - see the Protocol for the details. 19. Concomitant use of hormonal contraceptives which are metabolised through CYP 3A4, are not allowed as the sole measure to prevent pregnancy within 4 weeks prior to screening and until 1 week after the last IMP administration and progesterone-only hormonal contraception. 20. Known sensitivity to any components of the study products to be administered. 21. Previous participation to this study with at least 1 administration of the IMP. 22. History of drug or alcohol abuse within 2 years prior to screening. 23. Pregnant (e.g., positive serum pregnancy test) or females currently breastfeeding. 24. History or known concomitant solid tumours and/or haematological malignancies unless resolved in the ≥2 past years, except for basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, incidental histologic finding of prostate cancer (T1a or T1b according to the Classification of Malignant Tumours clinical staging system). 25. Vulnerable subjects. 26. Unable to take and absorb oral medications, unable to swallow Size 0 capsules. 27. Acute peptic stomach or duodenal ulcer in the previous 6 months before screening and/or healed after 3 months of proton-pump inhibitors therapy (or adequate standard of care therapy). 28. Occult or evident not controlled hemorrhages. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean change from baseline in haemolysis markers as measured by reduction of indirect bilirubin after 8 weeks of treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 8 weeks of the treatment. |
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E.5.2 | Secondary end point(s) |
- Mean change from baseline in haemolysis markers as measured by direct and total bilirubin, LDH, potassium, Hb and free haptoglobin after 8 weeks of treatment. - Frequency and severity of reported or observed AEs by SOC and PTs using MedDRA coded terms, indicating seriousness criteria and relatedness over 8 weeks of treatment. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 8 weeks of the treatment. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | 5 |
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 | 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 |
Lebanon |
United States |
France |
Greece |
United Kingdom |
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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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The overall end of trial is defined as the date of the last visit of the last patient participating in the trial and the end of patients data collection. |
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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 | 11 |
E.8.9.1 | In the Member State concerned days | 21 |
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 | 9 |