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

Phase 2

Completed

Conditions: Sickle Cell Disease

Interventions: Drug: VIT-2763 120 mg
Drug: VIT-2763 360 mg
Drug: VIT-2763 240 mg
Drug: Placebo BID
Drug: Placebo TID

Registration Number: NCT04817670

Lead Sponsor: Vifor (International) Inc.

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 25

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1	VIT-2763 120 mg	Participants receive VIT-2763 60 mg, twice a day during 8 weeks.
Cohort 3	VIT-2763 360 mg	Participants receive VIT-2763 120 mg, three times a day during 8 weeks.
Cohort 2	VIT-2763 240 mg	Participants receive VIT-2763 120 mg, twice a day during 8 weeks.
Cohort 4a	Placebo BID	Participants receive a placebo, twice a day during 8 weeks.
Cohort 4b	Placebo TID	Participants receive a placebo, three times a day during 8 weeks.

Primary Outcome Measures

Name	Time	Method
Mean Change From Baseline in Haemolysis Marker (Indirect Bilirubin)	Baseline and after 8 weeks of treatment	Mean change from baseline in haemolysis markers was measured by reduction of indirect bilirubin.

Secondary Outcome Measures

Name	Time	Method
Mean Change From Baseline in Haemolysis Marker (Direct and Total Bilirubin)	Baseline and after 8 weeks of treatment	Mean change from baseline in haemolysis markers was measured by direct and total bilirubin.
Mean Change From Baseline in Haemolysis Marker (Lactate Dehydrogenase)	Baseline and after 8 weeks of treatment	Mean change from baseline in haemolysis markers was measured by lactate dehydrogenase.
Mean Change From Baseline in Haemolysis Marker (Potassium)	Baseline and after 8 weeks of treatment	Mean change from baseline in haemolysis markers was measured by potassium.
Mean Change From Baseline in Haemolysis Marker (Hemoglobin and Haptoglobin)	Baseline and after 8 weeks of treatment	Mean change from baseline in haemolysis markers was measured by hemoglobin and haptoglobin.
Number of Participants With Treatment-emergent Adverse Events (TEAEs), TEAEs Related to IMP and by Severity of TEAEs	From first dose of study drug up to 12 weeks	TEAEs were defined as adverse events (AEs) with an onset date later or on the same date as first investigational medicinal product (IMP) intake. The severity grading was determined according to the Common Terminology Criteria for AEs, where the Common Terminology Criteria grades relate to severity as follows: Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe, Grade 4: Life-threatening and Grade 5: Death.

Trial Locations

Locations (22): Investigator Site 801
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Colombes, France
Investigator Site 802
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Lyon, France
Investigator Site 101
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Baabda, Lebanon
Investigator Site 606
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Liverpool, United Kingdom
Investigator Site 603
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London, United Kingdom
Investigator Site 608
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London, United Kingdom
Investigator Site 601
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London, United Kingdom
Investigator Site 605
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London, United Kingdom
Investigator Site 607
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Manchester, United Kingdom
Investigator site 301
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Athens, Greece
Investigator Site 302
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Patra, Greece
Investigator Site 102
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Beirut, Lebanon
Investigator Site 103
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Tripoli, Lebanon
Investigator Site 305
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Athens, Greece
Investigator Site 709
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Birmingham, Alabama, United States
Investigator Site 708
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Los Angeles, California, United States
Investigator Site 706
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Hollywood, Florida, United States
Investigator Site 703
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Chicago, Illinois, United States
Investigator Site 701
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Greenville, North Carolina, United States
Investigator Site 713
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Aurora, Colorado, United States
Investigator Site 702
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Milwaukee, Wisconsin, United States
Investigator Site 711
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Charleston, South Carolina, United States