Efficacy and Safety Study of Multiple Doses of VIT-2763 in Adults With Transfusion-dependent Beta-thalassemia

A Phase 2b, Double-blind, Randomised, Placebo-controlled, Multicentre Study to Assess the Efficacy and Safety of VIT-2763 Multiple Doses in Adults With Transfusion-dependent Beta-thalassaemia

The main purpose of this study is to evaluate the efficacy of 3 multiple doses of VIT-2763 as measured by the reduction in red blood cell (RBC) transfusion burden from Week 13 to Week 24, to identify the most efficacious and safe dose.

All patients giving written informed consent will undergo a 12-week screening period to determine eligibility for study entry. At Day 1, patients who meet the eligibility requirements will be randomized in a double-blind manner to 1 of 4 treatment groups: VIT-2763 60 mg (once daily), 60 mg (twice daily), or 120 mg (twice daily) or placebo.

The randomisation will be stratified (balanced allocation across treatment groups) according to β0/β0 genotype (yes/no).

The duration of the treatment with VIT-2763 or placebo is 24 weeks, after which patients will undergo a 12-week post-treatment follow-up period.

Inclusion Criteria:

• Body weight ≥40.0 kg and ≤100 kg at screening
• Documented diagnosis of beta-thalassemia or Hb E/beta-thalassemia
• Red blood cell (RBC) transfusion dependence, defined as at least 6 RBC units in the 24 weeks prior to randomization and no transfusion-free period for ≥35 days during that period
• Ability to understand the requirements of the study and provide written informed consent

Exclusion Criteria:

• Documented diagnosis of Hb S/beta-thalassemia, alpha-thalassemia, or delta beta (δβ)-thalassemia, or hereditary persistence of foetal Hb.
• History of partial or total splenectomy within 4 months prior to screening.
• History of myocardial iron overload
• Chronic liver disease or history of liver cirrhosis
• Clinically relevant renal disease
• History or clinically important finding of cardiac disorders
• History of clinically significant lung disease
• Uncontrolled hypertension (> Grade 1 according to NCI CTCAE current version)
• Unable to take and absorb oral medications.
• Pregnancy or breastfeeding
• History of drug or alcohol abuse within 2 years prior to screening
• History or concomitant solid tumors and/or hematological malignancies unless resolved in the ≥5 past years.