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

NCT06726863 | Completed Phase 1

• 1 other identifier: CSL624_1005
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Volunteers

Keywords

Oral ferroportin inhibitor; Ferroportin transporter; Iron overload; Iron metabolism

Outcome Measures

Primary Outcomes (24)

• 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 Outcomes (22)

• 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

  At baseline and up to 25 days after treatment

• AUC0-24 of vamifeport PR1 and PR2 in Treatment Period 3 and 4

  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

  Before and up to 12 hours after dosing, in TP3 and TP4

Study Arms (7)

Treatment Period 1: Vamifeport IR Formulation Dose Level 1

EXPERIMENTAL

Participants will receive multiple doses of Vamifeport Immediate-release (IR) formulation at Dose level 1.

Drug: Vamifeport IRF

Treatment Period 2: Vamifeport PR1 Dose Level 2

EXPERIMENTAL

Participants will receive multiple doses of Vamifeport Prolonged-release formulation 1 (PR1) at Dose level 2.

Drug: Vamifeport PR1

Treatment Period 2: Vamifeport PR2 Dose Level 2

EXPERIMENTAL

Participants will receive multiple doses of Vamifeport Prolonged-release formulation 2 (PR2) at Dose level 2.

Drug: Vamifeport PR2

Treatment Period 3: Vamifeport PR1 Dose Level 3

EXPERIMENTAL

Participants will receive a single dose of Vamifeport PR1 at Dose level 3.

Drug: Vamifeport PR1

Treatment Period 3: Vamifeport PR2 Dose Level 3

EXPERIMENTAL

Participants will receive a single dose of Vamifeport PR2 at Dose level 3.

Drug: Vamifeport PR2

Treatment Period 4: Vamifeport PR1 Dose Level 3

EXPERIMENTAL

Participants will receive a single dose of Vamifeport PR1 at Dose level 3.

Drug: Vamifeport PR1

Treatment Period 4: Vamifeport PR2 Dose Level 3

EXPERIMENTAL

Participants will receive a single dose of Vamifeport PR2 at Dose level 3.

Drug: Vamifeport PR2

Interventions

Vamifeport IRF DRUG

Vamifeport IRF will be administered orally as per the dosing levels and formulations for respective treatment periods.

Also known as: CSL624

Treatment Period 1: Vamifeport IR Formulation Dose Level 1

Vamifeport PR1 DRUG

Vamifeport PR1 will be administered orally as per the dosing levels and formulations for respective treatment periods.

Also known as: CSL624

Treatment Period 2: Vamifeport PR1 Dose Level 2; Treatment Period 3: Vamifeport PR1 Dose Level 3; Treatment Period 4: Vamifeport PR1 Dose Level 3

Vamifeport PR2 DRUG

Vamifeport PR2 will be administered orally as per the dosing levels and formulations for respective treatment periods.

Also known as: CSL624

Treatment Period 2: Vamifeport PR2 Dose Level 2; Treatment Period 3: Vamifeport PR2 Dose Level 3; Treatment Period 4: Vamifeport PR2 Dose Level 3

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (1)

Investigator Site 82600083

Leeds, West Yorkshire, LS11, United Kingdom

Location

MeSH Terms

Conditions

Iron Overload

Condition Hierarchy (Ancestors)

Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Study Director

  CSL Behring

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a 4-treatment period study that uses three different models: Treatment Period 1 will be a single-arm model, Treatment Period 2 will be a parallel-group model, and Treatment Periods 3 and 4 will be crossover models.

Study Record Dates

• First Submitted: December 6, 2024
• First Posted: December 10, 2024
• Study Start: November 22, 2024
• Primary Completion: January 27, 2025
• Study Completion: February 1, 2025
• Last Updated: June 27, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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
• 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.

Locations

GB (1)