Pharmacokinetics and Pharmacodynamics of Two Prolonged-release Formulations of Vamifeport in Healthy Adults

A Phase 1, Randomized, Open-label Study to Characterize the Pharmacokinetics, Pharmacodynamics, and Safety of Vamifeport After Multiple Oral Administration of One Immediate-release Formulation and After Single and Multiple Oral Administration of Two Prolonged-release Formulations in Healthy Adult Subjects

This is a phase 1, single-center, randomized, open-label study to characterize the pharmacokinetics (PK), pharmacodynamics (PD), and safety of vamifeport after multiple oral administrations of one immediate-release (IR) formulation and after single and multiple oral administrations of two prolonged-release (PR) formulation in healthy adult participants.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Vamifeport IRF; Drug: Vamifeport PR1; Drug: Vamifeport PR2

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS11
      • Investigator Site 82600083

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Aged greater than or equal to (>=) 18 to less than or equal to (<=) 60 years when providing written informed consent.
• Healthy, as determined by the investigator based on review of defined assessments during Screening.
• Body weight between 50 and 100 kilograms (kg) (inclusive) and body mass index within the range 18.0 to 32.0 kg per meter squared (kg/m2) (inclusive) at Screening and Day -1.

Exclusion Criteria:

• Any clinically relevant abnormal 12-lead ECG finding at Screening or Day -1 (as deemed by the investigator).
• Serum ferritin of < 30 nanograms per milliliter (ng/mL) or > 300 ng/mL for assigned male at birth (AMAB) subjects or <16 ng/mL or > 300 ng/mL for assigned female at birth (AFAB) subjects at Screening or Day -1.
• Hemoglobin < 13 grams per deciliter (g/dL) (8.1 millimoles per liter [mmol/L]) for AMAB subjects or 12 g/dL (7.5 mmol/L) for AFAB subjects at Screening or Day -1.
• Blood draw or donation of blood (>= 450 mL) within 3 months before Screening, plasma from 2 weeks before Screening, or platelets from 6 weeks before Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Period 1: Vamifeport IR Formulation Dose Level 1; Participants will receive multiple doses of Vamifeport Immediate-release (IR) formulation at Dose level 1.	Drug: Vamifeport IRF; Vamifeport IRF will be administered orally as per the dosing levels and formulations for respective treatment periods.; Other Names: CSL624
Experimental: Treatment Period 2: Vamifeport PR1 Dose Level 2; Participants will receive multiple doses of Vamifeport Prolonged-release formulation 1 (PR1) at Dose level 2.	Drug: Vamifeport PR1; Vamifeport PR1 will be administered orally as per the dosing levels and formulations for respective treatment periods.; Other Names: CSL624
Experimental: Treatment Period 2: Vamifeport PR2 Dose Level 2; Participants will receive multiple doses of Vamifeport Prolonged-release formulation 2 (PR2) at Dose level 2.	Drug: Vamifeport PR2; Vamifeport PR2 will be administered orally as per the dosing levels and formulations for respective treatment periods.; Other Names: CSL624
Experimental: Treatment Period 3: Vamifeport PR1 Dose Level 3; Participants will receive a single dose of Vamifeport PR1 at Dose level 3.	Drug: Vamifeport PR1; Vamifeport PR1 will be administered orally as per the dosing levels and formulations for respective treatment periods.; Other Names: CSL624
Experimental: Treatment Period 3: Vamifeport PR2 Dose Level 3; Participants will receive a single dose of Vamifeport PR2 at Dose level 3.	Drug: Vamifeport PR2; Vamifeport PR2 will be administered orally as per the dosing levels and formulations for respective treatment periods.; Other Names: CSL624
Experimental: Treatment Period 4: Vamifeport PR1 Dose Level 3; Participants will receive a single dose of Vamifeport PR1 at Dose level 3.	Drug: Vamifeport PR1; Vamifeport PR1 will be administered orally as per the dosing levels and formulations for respective treatment periods.; Other Names: CSL624
Experimental: Treatment Period 4: Vamifeport PR2 Dose Level 3; Participants will receive a single dose of Vamifeport PR2 at Dose level 3.	Drug: Vamifeport PR2; Vamifeport PR2 will be administered orally as per the dosing levels and formulations for respective treatment periods.; Other Names: CSL624

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasma concentration-time course profiles of vamifeport	Treatment Period (TP) 2: Before and after dosing on Day 4 (up to 12 hours), Day 8 (up to 48 hours), Before dosing on Day 5, 6, 7 TP 3: Before and after dosing on Day 13 (up to 48 hours) TP 4: Before and after dosing on Day 16 (up to 48 hours)
Maximum plasma concentration (Cmax) of first and last dose of vamifeport PR1 and PR2 in Treatment Period 2	TP2: Before, and up to 48 hours after, both the first and the last dose
Time to reach Cmax (Tmax) of first and last dose vamifeport PR1 and PR2 in Treatment Period 2	TP 2: Before, and up to 48 hours after, both the first and the last dose
Area under the plasma concentration curve from time zero to 12 hours (AUC0-12) of first and last dose of vamifeport PR1 and PR2 in Treatment Period 2	TP 2: Before, and up to 48 hours after, both the first and the last dose
Trough concentration (Ctrough) of first dose of vamifeport PR1 and PR2 in Treatment Period 2	Before and up to 24 hours after the first dose in TP2
AUC from time zero to infinity (AUC0-inf) of last dose of vamifeport PR1 and PR2 in Treatment Period 2	TP 2: Before, and up to 48 hours after last dose
AUC from time zero to time tlast (AUC0-last) of last dose of vamifeport PR1 and PR2 in Treatment Period 2	TP 2: Before, and up to 48 hours after last dose
AUC from time zero to 8 hours (AUC0-8) and 24 hours (AUC0-24) of last dose of vamifeport PR1 and PR2 in Treatment Period 2	TP 2: Before, and up to 8 and 24 hours after last dose
Plasma concentration at 12 hours (Conc [t=12]) of last dose of vamifeport PR1 and PR2 in Treatment Period 2	TP 2: Before and up to 12 hours after last dose
Apparent clearance (CL/F) of last dose of vamifeport PR1 and PR2 in Treatment Period 2	TP 2: Before, and up to 48 hours after last dose
Apparent volume of distribution at steady state (Vss/F) of last dose of vamifeport PR1 and PR2 in Treatment Period 2	TP 2: Before, and up to 48 hours after last dose
Accumulation ratio (Rac) of Cmax between first and last dose of vamifeport PR1 and PR2 in Treatment Period 2	TP 2: Before, and up to 48 hours after first and last dose
Rac(Ctrough/Conc[t=12]) between first and last dose of vamifeport PR1 and PR2 in Treatment Period 2	TP 2: Before, and up to 12 hours after first and last dose
Rac (AUC0-12) between first and last dose of vamifeport PR1 and PR2 in Treatment Period 2	TP 2: Before, and up to 12 hours after first and last dose
Half-life (t1/2) after last dose of vamifeport PR1 and PR2 in Treatment Period 2	TP 2: Before, and up to 48 hours after last dose
Cmax of vamifeport PR1 and PR2 in Treatment Period 3 and 4	Before and up to 48 hours after dosing, in TP3 and TP4
Tmax of vamifeport PR1 and PR2 in Treatment Period 3 and 4	Before and up to 48 hours after dosing, in TP3 and TP4
AUC0-inf of vamifeport PR1 and PR2 in Treatment Period 3 and 4	Before and up to 48 hours after dosing, in TP3 and TP4
AUC0-last of vamifeport PR1 and PR2 in Treatment Period 3 and 4	Before and up to 48 hours after dosing, in TP3 and TP4
AUC0-8, AUC0-12 and AUC0-24 of vamifeport PR1 and PR2 in Treatment Period 3 and 4	Before and up to 8, 12 and 24 hours after dosing, in TP3 and TP4
Plasma Concentration at 8 hours (Conc [t=8]), 12 hours (Conc [t=12]) and 24 hours (Conc [t=24]) of vamifeport PR1 and PR2 in Treatment Period 3 and 4	Before and up to 8, 12 and 24 hours after dosing, in TP3 and TP4
CL/F of vamifeport PR1 and PR2 in Treatment Period 3 and 4	Before and up to 48 hours after dosing, in TP3 and TP4
t1/2 of vamifeport PR1 and PR2 in Treatment Period 3 and 4	Before and up to 48 hours after dosing, in TP3 and TP4
Apparent volume of distribution (Vz/F) of vamifeport PR1 and PR2 in Treatment Period 3 and 4	Before and up to 48 hours after dosing, in TP3 and TP4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-emergent (TE): adverse event (AE), AE by severity, AE related to vamifeport, and serious AE		Up to 25 days after treatment
Percentage of participants with TEAE, AE by severity, AE related to vamifeport, and serious AE		Up to 25 days after treatment
Number of participants with clinically significant change from Baseline in clinical laboratory safety tests, 12 lead Electrocardiogram (ECG), and vital signs	The clinical laboratory safety tests include biochemistry, hematology, urinalysis.	At baseline and up to 25 days after treatment
AUC0-24 of vamifeport PR1 and PR2 in Treatment Period 3 and 4	Comparison of AUC0-24 between PR1 and PR2	Before and up to 24 hours after dosing, in TP3 and TP4
AUC0-12 of vamifeport PR1 and PR2 in Treatment Period 3 and 4	Comparison of AUC0-12 between PR1 and PR2	Before and up to 12 hours after dosing, in TP3 and TP4
AUC0-inf of vamifeport PR1 and PR2 in Treatment Period 3 and 4	Comparison of AUC0-inf between PR1 and PR2	Before and up to 48 hours after dosing, in TP3 and TP4
Conc (t=12) of vamifeport PR1 and PR2 in Treatment Period 3 and 4	Comparison of conc(t=12) between PR1 and PR2	Before and up to 12 hours after dosing, in TP3 and TP4
Conc (t=24) of vamifeport PR1 and PR2 in Treatment Period 3 and 4	Comparison of conc(t=24) between PR1 and PR2	Before and up to 24 hours after dosing, in TP3 and TP4
Cmax of vamifeport PR1 and PR2 in Treatment Period 3 and 4	Comparison of cmax between PR1 and PR2	Before and up to 48 hours after dosing, in TP3 and TP4
Tmax of vamifeport PR1 and PR2 in Treatment Period 3 and 4	Comparison of tmax between PR1 and PR2	Before and up to 48 hours after dosing, in TP3 and TP4
Absolute values of serum iron		Before and up to 48 hours after dosing in TP2, TP3 and TP4
Absolute values of transferrin saturation (TSAT)		Before and up to 48 hours after dosing in TP2, TP3 and TP4
Change from baseline of serum iron		Before and up to 48 hours after dosing in TP2, TP3 and TP4
Change from baseline of TSAT		Before and up to 48 hours after dosing in TP2, TP3 and TP4
Maximum percentage change from baseline (Emax) of serum iron		Before and up to 48 hours after dosing in TP2, TP3 and TP4
Emax of TSAT		Before and up to 48 hours after dosing in TP2, TP3 and TP4
Time to Emax (TEmax) of serum iron		Before and up to 48 hours after dosing in TP2, TP3 and TP4
TEmax of TSAT		Before and up to 48 hours after dosing in TP2, TP3 and TP4
Time below baseline of serum iron		Before and up to 48 hours after dosing in TP2, TP3 and TP4
Time below baseline of TSAT		Before and up to 48 hours after dosing in TP2, TP3 and TP4
AUC below baseline of serum iron		Before and up to 48 hours after dosing in TP2, TP3 and TP4
AUC below baseline of TSAT		Before and up to 48 hours after dosing in TP2, TP3 and TP4

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Study Director, CSL Behring

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2024
• Primary Completion (Actual): January 27, 2025
• Study Completion (Actual): February 1, 2025

Study Registration Dates

• First Submitted: December 6, 2024
• First Submitted That Met QC Criteria: December 6, 2024
• First Posted (Actual): December 10, 2024

Study Record Updates

• Last Update Posted (Actual): June 27, 2025
• Last Update Submitted That Met QC Criteria: June 26, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Iron overload; Iron metabolism; Oral ferroportin inhibitor; Ferroportin transporter
• Other Study ID Numbers: CSL624_1005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: CSL will consider on a case-by-case basis requests to share Individual Patient Data (IPD) with external bona-fide, qualified scientific and medical researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.
• IPD Sharing Time Frame: Requests for IPD will generally be considered once review by major regulatory authorities (i.e. FDA, EMA) is complete and the primary publication is available

IPD Sharing Access Criteria

Proposed research should seek to answer a previously unanswered important medical or scientific question.

Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.

If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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