Study to Assess Efficacy and Safety of VIT-2763 (Vamifeport) in Subjects With Sickle Cell Disease

A Phase 2a, Double-blind, Randomised, Placebo-controlled, Efficacy, and Safety Study of Multiple Doses of VIT-2763 in Subjects With Sickle Cell Disease (ViSionSerenity)

The purpose of this study is to investigate the effect of VIT-2763 on markers of hemolysis (breakdown in red blood cells) in sickle cell disease (SCD). The safety, tolerability and clinical beneficial effects of VIT-2763 for the treatment of SCD are also explored.

At randomization/baseline, participants are randomized into 3 VIT-2763 dose groups to receive either 60 mg twice daily (BID) (Cohort 1), or 120 mg BID (Cohort 2), or 120 mg 3 times daily (TID) (Cohort 3) and 2 placebo groups (BID, Cohort 4a or TID, Cohort 4b).

The expected duration of patient participation is a maximum of 16 weeks, including a non-treatment screening period of up to 4 weeks, and 8-week treatment period, and a 4-week safety follow-up period.

Inclusion Criteria:

• Male or female subjects with confirmed diagnosis of SCD, including only HbS/S or HbS/βT0 genotype.
• Subjects who had at least 1 and no more than 10 vaso-occlusive crises (VOC) episodes reported within 12 months prior to screening.
• Body weight ≥40 kg and ≤120 kg at screening and baseline.
• Subjects on concomitant hydroxyurea must be on a stable dose (mg/kg) for ≥3 months prior to screening Visit V1
• Female subjects of childbearing potential, must have negative pregnancy, must have stopped breastfeeding as of first dose, and must either commit to true abstinence from heterosexual contact or must be willing to use adequate contraceptive precautions.
• Male subjects must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential

Exclusion Criteria:

• Hb level <6.0 g/dl or >10.4 g/dl for female participants and >11.0 g/dl for male participants, at screening Visit V1
• Having received red blood cell (RBC) transfusion therapy within 4 weeks prior to screening, or ongoing or planned RBC transfusion therapy during the course of the study
• Low levels of Ferritin or transferrin saturation or total iron-binding capacity at screening
• Subjects being hospitalized for SCD-related events within 14 days before the screening visit
• Chronic liver disease or history of liver cirrhosis, and/or high levels of alanine aminotransferase or aspartate aminotransferase at baseline
• Low estimated glomerular filtration rate, and/or significant high urinary albumin/creatinine ratio at screening or on chronic dialysis.
• Newly diagnosed folate deficiency anemia, which is considered clinically relevant by the Investigator at screening
• Any history or clinically important finding of cardiac or pulmonary disorders
• Family history of long-QT syndrome or sudden death without a preceding diagnosis of a condition that could be causative of sudden death
• 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 a later time point.
• Concomitant use of certain hormonal contraceptives as defined in the study protocol, are not allowed within 4 weeks prior to screening and until 1 week after the last administration of the study drug and the use of progesterone-only hormonal contraception as the sole measure to prevent pregnancy.
• Pregnant or females currently breastfeeding.
• 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
• Unable to take and absorb oral medications
• Acute peptic stomach or duodenal ulcer in the previous 6 months before screening and/or healed after 3 months of treatment.
• Uncontrolled hemorrhages