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

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

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.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: VIT-2763 120 mg; Drug: VIT-2763 240 mg; Drug: VIT-2763 360 mg; Drug: Placebo BID; Drug: Placebo TID

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: VIT-2763-SCD-202 Clinical Study Team; Phone Number: +41 588 518 00; Email: clinicaltrials@cslbehring.com

Study Locations

• France
  • Colombes, France, 92700
    • Investigator Site 801
  • Lyon, France, 690003
    • Investigator Site 802
• Greece
  • Athens, Greece, 11527
    • Investigator Site 305
  • Athens, Greece, GR-11527
    • Investigator site 301
  • Patra, Greece
    • Investigator Site 302
• Lebanon
  • Baabda, Lebanon
    • Investigator Site 101
  • Beirut, Lebanon
    • Investigator Site 102
  • Tripoli, Lebanon
    • Investigator Site 103
• United Kingdom
  • Liverpool, United Kingdom, L9 7AL
    • Investigator Site 606
  • London, United Kingdom, SE59RS
    • Investigator Site 603
  • London, United Kingdom, W12 0HS
    • Investigator Site 608
  • London, United Kingdom
    • Investigator Site 601
  • London, United Kingdom
    • Investigator Site 605
  • Manchester, United Kingdom, M13 9WL
    • Investigator Site 607
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233-2110
      • Investigator Site 709
  • California
    • Los Angeles, California, United States, 90027
      • Investigator Site 708
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Investigator Site 713
  • Florida
    • Hollywood, Florida, United States, 33023
      • Investigator Site 706
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Investigator Site 703
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Investigator Site 701
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Investigator Site 711
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Investigator Site 702

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Participants receive VIT-2763 60 mg, twice a day during 8 weeks.	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.; Other Names: Vamifeport
Experimental: Cohort 2; Participants receive VIT-2763 120 mg, twice a day during 8 weeks.	Drug: 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.; Other Names: Vamifeport
Experimental: Cohort 3; Participants receive VIT-2763 120 mg, three times a day during 8 weeks.	Drug: 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.; Other Names: Vamifeport
Placebo Comparator: Cohort 4a; Participants receive a placebo, twice a day during 8 weeks.	Drug: 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 Comparator: Cohort 4b; Participants receive a placebo, three times a day during 8 weeks.	Drug: 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Vifor (International) Inc.
• Collaborators: Fortrea
• Investigators: Study Director: Ricardo Hermosilla, PhD, Vifor (International) Inc.

Publications and helpful links

General Publications

• 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2021
• Primary Completion (Actual): March 7, 2024
• Study Completion (Actual): March 7, 2024

Study Registration Dates

• First Submitted: March 23, 2021
• First Submitted That Met QC Criteria: March 23, 2021
• First Posted (Actual): March 26, 2021

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: anemia; sickle cell disease; vamifeport
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: VIT-2763-SCD-202; 2020-005072-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No