A study to the assess safety, tolerability and the effect of VIT-2763 on blood markers, symptoms and quality of life in patients with non-transfusion dependent beta-thalassemia

Phase 1

• Conditions: MedDRA version: 20.0Level: LLTClassification code 10074355Term: Non-transfusion dependent thalassaemiaSystem Organ Class: 100000004850; on-transfusion Dependent Beta-thalassaemia.; Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

• Registration Number: EUCTR2019-002221-29-GR
• Lead Sponsor: Vifor (International) Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-02-25
• Last Update Posted: 24 January 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 36

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 packedRBCs and last RBC transfusion must have been received =14 days prior to randomisation).
Note: Subjects who are supposed to receive RBC transfusions after randomization 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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 12
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 23
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion Criteria

1. Documented diagnosis of 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 ICT or subjects on prior ICT when discontinued less than 4 weeks prior randomisation. If ICT was discontinued =4 weeks prior randomization the subject is eligible.
3. ICT naïve subjects with serum ferritin <150 ng/ml and/or documented LIC =1 mg/g liver dry weight assessed through MRI, or subjects on prior ICT with serum ferritin <300 ng/ml and/or documented LIC <3 mg/g liver dry weight assessed through MRI.
Note: If documented LIC MRI scans retrieved within 24 months prior to randomization are not available per local practice, serum ferritin will be used only to document iron overload status.
4. Subjects with TSAT <30%.
5. Subjects with documented LIC >15 mg/g liver dry weight assessed through MRI, or a documented myocardial T2* <20 ms, if available per local practice and retrieved within 24 months prior to randomization.
6. Adult or adolescent subjects with body weight <40.0 kg or >100 kg at screening.
7. Chronic liver disease and/or ALT, AST or GGT above 3-fold the 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. eGFR <30 ml/min/1.73 m2 (according to chronic kidney disease classification Stage 4 or higher), and/or significant albuminuria >30 mg/mmol. eGFR should be estimated according to Chronic Kidney Disease Epidemiology Collaboration formula (CKI-EPI) in adults, and Schwartz formula in adolescents.
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 history of partial or total splenectomy within 6 months prior to screening.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified