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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: VIT-2763 120 mg
* Drug: VIT-2763 360 mg
* Drug: VIT-2763 240 mg
* Drug: Placebo BID
* Drug: Placebo TID


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Participants receive VIT-2763 60 mg, twice a day during 8 weeks. | Drug: VIT-2763 120 mg<br>* Participants receive 2 capsules of VIT-2763 30 mg in the morning and in the evening, for 8 weeks. Capsules are to be taken orally.<br>* Other names: Vamifeport;|
| Experimental: Cohort 2<br>Participants receive VIT-2763 120 mg, twice a day during 8 weeks. | Drug: VIT-2763 240 mg<br>* Participants receive 2 capsules of VIT-2763 60 mg in the morning and in the evening, for 8 weeks. Capsules are to be taken orally.<br>* Other names: Vamifeport;|
| Experimental: Cohort 3<br>Participants receive VIT-2763 120 mg, three times a day during 8 weeks. | Drug: VIT-2763 360 mg<br>* Participants receive 2 capsules of VIT-2763 60 mg in the morning, in the afternoon and in the evening for 8 weeks. Capsules are to be taken orally.<br>* Other names: Vamifeport;|
| Placebo Comparator: Cohort 4a<br>Participants receive a placebo, twice a day during 8 weeks. | Drug: Placebo BID<br>* Participants receive 2 capsules of placebo in the morning and in the evening, for 8 weeks. Capsules are to be taken orally.<br>|
| Placebo Comparator: Cohort 4b<br>Participants receive a placebo, three times a day during 8 weeks. | Drug: Placebo TID<br>* Participants receive 2 capsules of Placebo in the morning, in the afternoon and in the evening, for 8 weeks. Capsules are to be taken orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline in haemolysis markers | Measured by reduction of indirect bilirubin (umol/L)(calculated) | 8 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline in haemolysis markers | Measured by direct and total bilirubin (umol/L) | 8 weeks of treatment | 
| Mean change from baseline in haemolysis markers | Measured by lactate dehydrogenase (LDH) (IU/L) | 8 weeks of treatment | 
| Mean change from baseline in haemolysis markers | Measured by potassium (mmol/L) | 8 weeks of treatment | 
| Mean change from baseline in haemolysis markers | Measured by Hemoglobin (Hb) level (g/L) | 8 weeks of treatment | 
| Mean change from baseline in haemolysis markers | Measured by free haptoglobin (umol/L) | 8 weeks of treatment | 
| Frequency and severity of reported or observed adverse events (AEs) | By system organ class (SOC) and preferred terms (PTs) using Medical Dictionary for Regulatory Activities (MedDRA) coded terms, indicating seriousness criteria and relatedness | 8 weeks of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anemia, sickle cell disease, vamifeport