sickle cell disease (SCD) (sickle haemoglobin (HbS)/S or HbS/ßT0genotype) sickle cell disease
Conditions
Interventions
Male or female Adults(18-50 years) with sickle cell disease (SCD) (sickle haemoglobin (HbS)/S or HbS/ßT0genotype).
At randomisation/baseline (Part A), 25 subjects with SCD will be randomised in a 1:1:
whereas, subjects in Cohort 1b and Cohort 2b will continue with an increased dose of VIT-2763, 60 mg and 120 mg, respectively.
Subjects randomised to placebo during Part A (Cohort 3) will continue unc
? Treatment Group 1a: 1 capsule of 30 mg VIT-2763 in the morning and 1 capsule of placebo in the evening for 8 weeks ? Treatment Group 1b: 1 capsule of 30 mg VIT-2763 in the morning and 1 capsule of p
VIT-2763
Sponsors
Vifor (International) Inc.
Eligibility
Sex/Gender
All
Age
18 Years to 50 Years
Inclusion criteria
Inclusion criteria: 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 HbS/S or HbS/ßT0 genotype. 4. Subjects who had at least 1 and no more than 6 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 analgesics for moderate to severe pain. 5. 18 to 50 years of age inclusive at the time of screening. 6. Body weight =50 kg and =100 kg at screening and baseline. 7. Absolute reticulocyte count and percentage reticulocyte count >1.5 × upper limit of normal (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 and before randomisation, 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 subjects’ usual and preferred lifestyle, and periodic abstinence (calendar, symptothermal, postovulation methods) is not an acceptable method of contraception. Female subjects must agree to use adequate contraception during the study and for 1 month after the last dose of investigational medicinal product (IMP) 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 cytochrome P450 (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 andapproved alternatives. 10. Male subjects must practice true abstinence (abstinence should only be used as a contraceptive method if it is in line with the subjects’ usual and preferred lifestyle, and it is continuous throughout the study) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, and for at least 1 month–sufficiently exceeding 5 times the mean t1/2 of VIT-2763 based on multiple dose human PK data following IMP discontinuation, even if he has und
Exclusion criteria
Exclusion criteria: Exclusion Criteria: 1. Subjects with confirmed diagnosis of HbS/ßT+ genotype or HbSC disease. 2. Hb level 10.4 g/dl at screening Visit V1 (based on local laboratory value). Note: The Hb value at screening Visit V1 will be used for eligibility determination. However, the baseline Hb value determined at Visit V2 (Day 1 pre-dose) also needs to be within the above specified range. 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. Ferritin level 30 mg/g (>3.39 mg/mmol) at screening or on chronic dialysis. Note: eGFR should be estimated according to Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI). 8. Newly diagnosed folate deficiency anaemia (i.e., folic acid 0.21 seconds • Evidence or history of second- or third-degree atrioventricular block • QRS interval >0.12 seconds 13. 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. 14. Clinically significant bacterial, fungal, parasitic, or viral infection which requires therapy. Note: A subject meeting this criterion should delay screening and/or enrolment for a minimum of 2 weeks, or if excluded can be re-screened at maximum 2 times at a later time point. • Known history, and/or positive result on screening for hepatitis B surface antigen, hepatitis B virus, hepati
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Name: Mean change in heamolysis marker;Timepoints: from baseline to after 8 weeks treatment;Measure: reduction of indirect bilirubin | — |
Secondary
| Measure | Time frame |
|---|---|
| Name: Frequency and severity of reported or observed AEs by SOC and PTs;Timepoints: up to 4 weeks after EoT;Measure: All AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA);Name: Changes in clinical laboratory safety tests;Timepoints: After 2, 4, 6, and 8 weeks of treatment and 4 weeks after EoT;Measure: serum biochemistry, safety haematology, and urinalysis;Name: Changes in 12-Lead ECG;Timepoints: after 2, 4, 6, and 8 weeks of treatment and 4 weeks after EoT.;Measure: ventricular rate, PR interval, QRS duration, QT interval and QTcF;Name: Changes in blood inflammatory markers;Timepoints: from baseline after 2, 4, 6, and 8 weeks of treatment and 4 weeks after EoT;Measure: high sensitivity C-reactive protein, interleukin 1 and interleukin 6, tumour necrosis factor alpha, soluble vascular cell adhesion molecule 1, endothelin-1, soluble platelet-selectin, and xanthine oxidase;Name: Assessment of iron-related parameters and markers of erythropoiesis;Timepoints: from baseline after 2, 4, 6, and 8 weeks of treatment and 4 weeks after EoT;Measure: total serum iron, serum ferritin, serum transferrin, calculated TSAT, hepcidin, and erythropoietin;Name: Change in patient reported outcomes;Timepoints: from baseline after 2, 4, 6 and 8 weeks of treatment.;Measure: using ASCQ-Me;Name: Changes in abnormal RBCs (sickling);Timepoints: baseline after 2, 4, 6 and 8 weeks of treatment and 4 weeks after EoT.;Measure: peripheral blood smear;Name: Number of VOC episodes and visceral infarctions;Timepoints: over 8 weeks of treatment and 4 weeks after EoT.;Measure: VOC episodes;Name: PK parameters;Timepoints: from pre-dose trough to 1 hour and 3 hours post-morning dose at selected study visits.;Measure: Cmax, clearance, distribution volume, AUC;Name: Changes in haematological indices;Timepoints: from baseline after 2, 4, 6, and 8 weeks of treatment and 4 weeks after EoT.;Measure: Hb concentration, RBC count, Hct, MCV, MCH, MCHC, CHCM, RDW, WBC analyses includi | — |
Countries
Greece, Lebanon, United Kingdom, United States of America
Contacts
Public ContactAziz Zoghbi
Regional Manager
Outcome results
None listed