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

Sickle Cell Disease Clinical Trial

— ViSionSerenity  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04817670
• Other study ID #: VIT-2763-SCD-202
• Secondary ID: 2020-005072-34
• Status: Completed
• Phase: Phase 2
• Start date: June 9, 2021
• Est. completion date: March 7, 2024

Study information

• Verified date: March 2024
• Source: Vifor Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: March 7, 2024
• Est. primary completion date: March 7, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Male or female subjects with confirmed diagnosis of SCD, including only HbS/S or HbS/ßT0 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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Drug:
• VIT-2763 120 mg
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.
• VIT-2763 360 mg
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.
• VIT-2763 240 mg
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.
• Placebo BID
Participants receive 2 capsules of placebo in the morning and in the evening, for 8 weeks. Capsules are to be taken orally.
• Placebo TID
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.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Vifor (International) Inc.	Fortrea

Countries where clinical trial is conducted

United States,  France,  Greece,  Lebanon,  United Kingdom, 

References & Publications (1)

Nyffenegger N, Zennadi R, Kalleda N, Flace A, Ingoglia G, Buzzi RM, Doucerain C, Buehler PW, Schaer DJ, Durrenberger F, Manolova V. The oral ferroportin inhibitor vamifeport improves hemodynamics in a mouse model of sickle cell disease. Blood. 2022 Aug 18;140(7):769-781. doi: 10.1182/blood.2021014716. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean change from baseline in haemolysis markers	Measured by reduction of indirect bilirubin (umol/L)(calculated)	8 weeks of treatment
Secondary	Mean change from baseline in haemolysis markers	Measured by direct and total bilirubin (umol/L)	8 weeks of treatment
Secondary	Mean change from baseline in haemolysis markers	Measured by lactate dehydrogenase (LDH) (IU/L)	8 weeks of treatment
Secondary	Mean change from baseline in haemolysis markers	Measured by potassium (mmol/L)	8 weeks of treatment
Secondary	Mean change from baseline in haemolysis markers	Measured by Hemoglobin (Hb) level (g/L)	8 weeks of treatment
Secondary	Mean change from baseline in haemolysis markers	Measured by free haptoglobin (umol/L)	8 weeks of treatment
Secondary	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

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