Chronic anemia due to ineffective erythropoiesis (IE) in subjects with ß-thalassaemia thalassemia
Conditions
Interventions
The study will commence with enrolment and treatment of adult NTDT subjects(Cohort I). Adult subjects will be randomised in an 8:8:4 ratio to receive either VIT-2763 once daily (QD) or twice daily (BI
Adult subjects will be randomised in an 8:8:4 ratio to receive either VIT-2763 QD or BID or placebo at a dose of 120 mg for subjects with a body weight =60 kg or at a dose of 60 mg for subjects with a
cohort 1/2
Sponsors
Vifor (International) Inc.
Eligibility
Sex/Gender
All
Age
12 Years to 65 Years
Inclusion criteria
Inclusion criteria: 1. Documented diagnosis of NTDT, including a ß-thalassaemia intermedia-phenotype. 2. NTDT is defined as subjects having received <5 units of red blood cells (RBCs) during the 24-week period prior to randomisation/first drug administration of VIT-2763 or placebo (Day 1; 1 unit is defined as 200 to 350 ml of transfused packed RBCs and last RBC transfusion must have been received =14 days prior to randomisation). Note: Subjects who are supposed to receive RBC transfusions after randomisation in the Investigator’s opinion, and according to local practise, and having received at least 1 dose of VIT-2763, may be considered to stay on study treatment for safety reasons, and in case there are no tolerability concerns. Subjects will be censored for secondary efficacy. 3. Male and female adult NTDT subjects, 18-65 years of age inclusive (Cohort I only) at time of screening. 4. Male and female adolescent NTDT subjects, 12-17 years of age inclusive (Cohort II only) at time of screening. 5. Subjects must have a mean baseline Hb =11 g/dl, based on 2 consecutive measurements =1 week apart within 6 weeks prior to randomisation/baseline, and obtained Hb values show less than 10% relative difference (and equal or less than 1.0 g/dl absolute change between the highest and lowest value) between at least 2 measurements. Note: If there is 1 retrospective Hb value available for the subject at maximum of 2 weeks prior to screening (Day -28), the Hb value can be taken into consideration. A subject not meeting this criterion would be excluded but can be rescreened at maximum 2 times at a later time point.
Exclusion criteria
Exclusion criteria: 1. Documented diagnosis of transfusion dependent thalassaemia (TDT), including a beta-thalassaemia major phenotype (including ß0/ß0, ß+/ß+, ß0/ß+ genotype), and mixed compound heterozygous for sickling phenotype variants such as Hb S/ß-thalassaemia, or transfusion dependent non-deletional Hb H disease (i.e., Hb constant spring) or Hb C disease. 2. Subjects on concomitant iron chelation therapy (ICT) or subjects on prior ICT when discontinued less than 4 weeks prior randomisation. Note: If ICT was discontinued =4 weeks prior randomisation the subject is eligible. 3. ICT naïve subjects with serum ferritin 15 mg/g liver dry weight assessed through MRI, or a documented myocardial T2-star (T2*) 100 kg at screening and/or randomisation. 7. Chronic liver disease and/or alanine transaminase (ALT), aspartate transaminase (AST) or gamma-glutamyl transpeptidase (GGT) above 3-fold the upper limit of normal (ULN) range at screening. Note: A subject fulfilling this criterion will be excluded but can be rescreened at a later time point (in order to fulfil eligibility, =2 values within =1 week should be assessed and be within eligibility limits). 8. Estimated glomerular filtration rate (eGFR) 30 mg/mmol. eGFR should be estimated according to Cockcroft-Gault. 9. Newly diagnosed folate deficiency anaemia and/or Vitamin B12 megaloblastic anaemia. Subjects with known folate deficiency anaemia and/or Vitamin B12 megaloblastic anaemia who are on =12 weeks stable replacement therapy are eligible. Note: A subject fulfilling this criterion will be excluded but can be rescreened at a later time point. 10. Any history or clinically important finding of cardiac disorders, such as clinically relevant cardiac arrhythmia, cardiomyopathy, coronary disease, valve disorder, or heart failure according to New York Heart Association classification 3-4. 11. Subjects with partial or total splenectomy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Name: Reported or observed adverse events (AEs);Timepoints: last study contact Visit 9/Week 16.;Measure: by SOC and PT MedDRA coded term, by severity and relation to study product in each treatment group.;Name: Reported or observed serious adverse events (SAEs);Timepoints: 4 weeks (28+-4 days) following the last study drug administration.;Measure: by SOC and PT MedDRA coded term, by severity and relation to study product in each treatment group;Name: Changes in vital signs;Timepoints: screening Visit V1 and on Visits V3 to V8. Vital signs should be performed at V3 to V8 before IMP dosing, after a resting period of at least 5 minutes.;Measure: Blood pressure and pulse rate ;Name: Changes in clinical laboratory safety tests;Timepoints: over 12 week treatment ;Measure: haematology, serum biochemistry, coagulation, and urinalysis;Name: 12-Lead ECG;Timepoints: over 12 week treatment ;Measure: ventricular rate, PR interval, QRS duration, QT interval and QTcF;Name: Physical examination;Timepoints: Screening Visit V1 (i.e., Day -28 to -1) and on Visit V3 (Day 1), and V8 (Day 84);Measure: general appearance, head (eyes, ears, nose and throat), cardiovascular, respiratory, abdominal, musculoskeletal, neurological, lymph nodes, and skin. | — |
Secondary
| Measure | Time frame |
|---|---|
| Name: Assessment of iron parameters;Timepoints: from baseline over a 12-week period;Measure: total serum iron, serum ferritin, serum transferrin, calculated transferrin saturation (TSAT;Name: PK parameters;Timepoints: from pre-dose trough to 3 hours or 4 hours post-dose at selected study visits;Measure: Cmax, clearance, distribution volume, area under the curve (AUC) | — |
Countries
Lebanon
Contacts
Public ContactAziz Zoghbi
Regional Manager
Outcome results
None listed