Efficacy and Safety of Vamifeport in Adult Participants With Homeostatic Iron Regulator Gene (HFE)-Related Hereditary Hemochromatosis

A Phase 2, Multicenter, Randomized, Placebo-controlled, Double-blind Study of the Efficacy and Safety of Vamifeport in Adult Subjects With HFE-related Hereditary Hemochromatosis (FERROCLEAR Study)

This is a phase 2, multicenter, randomized, placebo-controlled, double-blind, parallel-group, proof-of-concept study to assess vamifeport in adult participants with homeostatic iron regulator gene-related hereditary hemochromatosis (HFE-HH). The primary objective of the study is to assess the effect of vamifeport treatment on magnetic resonance imaging (MRI)-based liver iron concentration (LIC) in adult participants with HFE-HH.

Study Overview

• Status: Recruiting
• Conditions: Homeostatic Iron Regulator Gene-related Hereditary Hemochromatosis
• Intervention / Treatment: Drug: Vamifeport; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 84
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Trial Registration Coordinator; Phone Number: +16108784697; Email: clinicaltrials@cslbehring.com

Study Locations

• Australia
  • Brisbane, Australia
    • Not yet recruiting
    • Royal Brisbane and Women's Hospital
  • Chandler, Australia
    • Not yet recruiting
    • Gallipoli Medical Research
  • Clayton, Australia
    • Not yet recruiting
    • Monash Medical Centre
  • Perth, Australia
    • Not yet recruiting
    • Trials West
  • Westmead, Australia, 2145
    • Not yet recruiting
    • Westmead Hospital for Medical Research
• Austria
  • Innsbruck, Austria
    • Not yet recruiting
    • Medical University of Innsbruck
  • Linz, Austria
    • Not yet recruiting
    • Ordensklinikum Linz - Barmherzige Schwestern
  • Vienna, Austria
    • Not yet recruiting
    • Medical University Vienna
• Belgium
  • Edegem, Belgium
    • Not yet recruiting
    • Universitair Ziekenhuis Antwerpen (UZA)
  • Ghent, Belgium
    • Not yet recruiting
    • Ghent University Hospital
  • Jette, Belgium
    • Not yet recruiting
    • UZ Brussel
  • Liège, Belgium
    • Not yet recruiting
    • Centre Hospitalier Universitaire de Liège (CHU de Liège)
  • Yvoir, Belgium
    • Not yet recruiting
    • CHU UCL Namur - Site Godinne
• Canada
  • Calgary, Canada
    • Not yet recruiting
    • Libin Cardiovascular Institute University of Calgary
  • Hamilton, Canada
    • Not yet recruiting
    • McMaster University-St. Josephs Healthcare Hamilton
  • Winnipeg, Canada
    • Not yet recruiting
    • University of Manitoba
• Czechia
  • Brno, Czechia
    • Not yet recruiting
    • Fakultní Nemocnice Brno
  • Ostrava, Czechia
    • Not yet recruiting
    • Fakultni nemocnice Ostrava
  • Prague, Czechia
    • Not yet recruiting
    • Institut Klinicke a Experimentalni Mediciny
• Denmark
  • Aarhus, Denmark
    • Not yet recruiting
    • Aarhus University Hospital
  • Copenhagen, Denmark
    • Not yet recruiting
    • Bispebjerg Hospital
  • Hvidovre, Denmark
    • Not yet recruiting
    • Copenhagen University Hospital - Hvidovre
• France
  • Bobigny, France
    • Not yet recruiting
    • Aphp Avicenne
  • Limoges, France
    • Not yet recruiting
    • Chu Dupuytren
  • Marseille, France
    • Not yet recruiting
    • CRMR Maladies du Globule Rouge, Hôpital de la Timone
  • Montpellier, France
    • Not yet recruiting
    • CHU de Montpellier- Hôpital Saint Eloi
  • Mulhouse, France
    • Not yet recruiting
    • GHRMSA
  • Pessac, France
    • Not yet recruiting
    • CHU de Bordeaux - Hôpital Haut Leveque
  • Pierre-Bénite, France
    • Not yet recruiting
    • Centre Hospitalier Lyon Sud/Hospices Civils de Lyon
  • Rennes, France
    • Not yet recruiting
    • Chu Rennes
  • Saint-Brieuc, France
    • Not yet recruiting
    • Centre Hospitalier de Saint Brieuc
  • Toulouse, France
    • Not yet recruiting
    • CHU Toulouse
  • Villejuif, France
    • Not yet recruiting
    • Hopital Paul Brousse
• Germany
  • Freiburg im Breisgau, Germany
    • Not yet recruiting
    • Universitätsklinikum Freiburg
  • Heidelberg, Germany
    • Not yet recruiting
    • University Hospital Heidelberg
  • Leipzig, Germany
    • Not yet recruiting
    • EUGASTRO GmbH
  • Weinheim, Germany
    • Not yet recruiting
    • MVZ für Innere Medizin Weinheim
• Ireland
  • Cork, Ireland
    • Not yet recruiting
    • Cork University Hospital
  • Dublin, Ireland
    • Not yet recruiting
    • Beaumont Hospital
  • Dublin, Ireland
    • Not yet recruiting
    • Connolly Hospital Blanchardstown
• Italy
  • Brindisi, Italy
    • Not yet recruiting
    • ASL Brindisi - Presidio Ospedaliero Di Summa - Perrino
  • Milan, Italy
    • Not yet recruiting
    • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
  • Modena, Italy
    • Not yet recruiting
    • University Hospital of Modena
  • Monza, Italy
    • Not yet recruiting
    • Fondazione IRCCS San Gerardo dei Tintori
  • Naples, Italy
    • Not yet recruiting
    • AORN Cardarelli
  • Verona, Italy
    • Not yet recruiting
    • University of Verona - Azienda Ospedaliera Universitaria Integrata Verona
• Netherlands
  • Maastricht, Netherlands
    • Not yet recruiting
    • Maastricht UMC
  • Nijmegen, Netherlands
    • Not yet recruiting
    • Radboud UMC
• New Zealand
  • Auckland, New Zealand, 1023
    • Not yet recruiting
    • Auckland City Hospital
  • Auckland, New Zealand, 2025
    • Recruiting
    • Aotearoa Clinical Trials Trust- Middlemore Hospital
• Poland
  • Warsaw, Poland
    • Not yet recruiting
    • Instytut Hematologii i Transfuzjologii
  • Wałbrzych, Poland
    • Not yet recruiting
    • Specjalistyczny Szpital im. Alfreda Sokolowskiego
  • Wroclaw, Poland
    • Not yet recruiting
    • Wojewodzki Szpital im. J Gromkowskiego we Wroclawiu
• Romania
  • Baloteşti, Romania
    • Not yet recruiting
    • Spitalul Clinic de Urgenta Prof Dr Agrippa Ionescu-Balotesti
  • Bistriţa, Romania
    • Not yet recruiting
    • Bistrița County Emergency Clinical Hospital
  • Bucharest, Romania
    • Not yet recruiting
    • Coltea Clinical Hospital
  • Cluj-Napoca, Romania
    • Not yet recruiting
    • L'Institute Oncologique Prof. Dr. Ion Chiricuta (IOCN)
  • Cluj-Napoca, Romania
    • Not yet recruiting
    • Prof. Dr.Octavian Fodor Regional Institute of Gastroenterology-Hepatology
• Spain
  • Badalona, Spain
    • Not yet recruiting
    • Hospital Universitari Germans Trias i Pujol
  • Barcelona, Spain
    • Not yet recruiting
    • Hospital Clinic Barcelona
  • LAS Palmas de GC, Spain
    • Not yet recruiting
    • HUGC Doctor Negrin
  • Madrid, Spain
    • Not yet recruiting
    • Hospital Universitario La Paz
  • Majadahonda, Spain
    • Not yet recruiting
    • Hospital Universitario Puerta de Hierro - Majadahonda
  • Manresa, Spain
    • Not yet recruiting
    • Althaia Foundation. Hospital Sant Joan de Deu de Manresa
  • Seville, Spain
    • Not yet recruiting
    • Hospital Universitario Virgen del Rocio
• Switzerland
  • Bern, Switzerland
    • Not yet recruiting
    • University Hospital Inselspital Bern
  • Lausanne, Switzerland
    • Not yet recruiting
    • Centre Hospitalier Universitaire Vaudois
  • Lugano, Switzerland
    • Recruiting
    • Epatocentro Ticino
• United Kingdom
  • Belfast, United Kingdom
    • Not yet recruiting
    • Royal Victoria Hospital
  • Bristol, United Kingdom
    • Recruiting
    • University Hospitals Bristol and Weston NHS trust, Bristol Haematology and Oncology Centre
  • Liverpool, United Kingdom
    • Not yet recruiting
    • Royal Liverpool University Hospital
  • London, United Kingdom
    • Not yet recruiting
    • King's College Hospital
  • London, United Kingdom
    • Not yet recruiting
    • St Thomas Hospital
  • Norwich, United Kingdom
    • Recruiting
    • Norfolk and Norwich University Hospital
  • Nottingham, United Kingdom
    • Not yet recruiting
    • Nottingham University Hospitals City Campus
  • Oxford, United Kingdom
    • Not yet recruiting
    • John Radcliffe Hospital - Oxford University Hospitals NHS
  • Plymouth, United Kingdom
    • Recruiting
    • Derriford Hospital
  • Southampton, United Kingdom
    • Not yet recruiting
    • University Hospital Southampton NHS Foundation Trust
  • Warwick, United Kingdom
    • Not yet recruiting
    • South Warwickshire University Foundation Trust
  • Glasgow City Region
    • Glasgow, Glasgow City Region, United Kingdom, SE5 9RS
      • Not yet recruiting
      • University Hospital Hairmyres-PPDS
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234-2165
      • Not yet recruiting
      • Banner MD Anderson
  • California
    • San Diego, California, United States, 92123
      • Not yet recruiting
      • Medical Oncology Associates of San Diego
    • San Diego, California, United States, 92108
      • Not yet recruiting
      • Infinity Clinical Trials
  • Florida
    • Jacksonville, Florida, United States, 32258
      • Recruiting
      • Green Leaf Clinical Trials
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5149
      • Recruiting
      • Indiana University Health University Hospital
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70836
      • Not yet recruiting
      • Ochsner Medical Complex - High Grove
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Not yet recruiting
      • Johns Hopkins University School of Medicine
    • Bethesda, Maryland, United States, 20817
      • Recruiting
      • American Oncology Partners, PA dba The Center for Cancer and Blood Disorders
    • Frederick, Maryland, United States, 21702-4337
      • Not yet recruiting
      • James M. Stockman Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Not yet recruiting
      • University of Michigan Health System (UMHS)
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • Recruiting
      • Aspirus St. Luke's Clinic - Duluth - Oncology & Hematology
  • New Jersey
    • Flemington, New Jersey, United States, 08822
      • Not yet recruiting
      • Hunterdon Hematology Oncology, LLC
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27517-7518
      • Not yet recruiting
      • University of North Carolina at Chapel Hill
    • Durham, North Carolina, United States, 27710-4000
      • Not yet recruiting
      • Duke University Medical Center (Duke South Clinics) -40 Duke Medicine Cir
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73174
      • Recruiting
      • Hightower Clinical - Oklahoma Cancer Center
  • Pennsylvania
    • York, Pennsylvania, United States, 17403-5060
      • Not yet recruiting
      • Cancer Care Associates of York
  • Utah
    • Murray, Utah, United States, 84107
      • Not yet recruiting
      • Intermountain Medical Center
  • Washington
    • Spokane, Washington, United States, 99202-2131
      • Recruiting
      • Washington State Univ Elson S. Floyd College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult (≥ 18 years) and has provided written informed consent.
• Confirmed diagnosis of HFE-HH in medical history.

• Evidence of iron overload as shown by:

  • TSAT > 45% (confirmed at 2 visits, at least 14 days apart) at Screening; and
  • Serum ferritin ≥ 200 nanogram per milliliter (ng/mL) and < 5000 ng/mL (confirmed at 2 visits, at least 14 days apart) at Screening; and
  • MRI-based LIC between 3 and 16 mg/g (53.7 and 286.5 millimol per kilogram [mmol/kg]) dry weight (dw) at Screening.
• Body mass index between 18.5 and 32 kilograms per meter squared (kg/m^2).

Exclusion Criteria:

• Clinically relevant laboratory abnormalities, 12-lead electrocardiogram (ECG) findings, or medical history.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vamifeport Low Dose; Participants will receive a low dose of vamifeport orally, twice daily (BID) up to Day 360.	Drug: Vamifeport; Vamifeport capsule administered orally.
Experimental: Vamifeport High Dose; Participants will receive a high dose of vamifeport orally, BID up to Day 360.	Drug: Vamifeport; Vamifeport capsule administered orally.
Placebo Comparator: Placebo; Participants will receive placebo matching vamifeport low and high doses orally, BID up to Day 360.	Drug: Placebo; Placebo capsule matching IP administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in magnetic resonance imaging (MRI)-based liver iron concentration (LIC)	At Baseline and Day 360

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-emergent adverse events (TEAEs)		Up to Day 390
Percentage of participants with TEAEs		Up to Day 390
Number of participants with treatment-emergent serious adverse events (SAEs)		Up to Day 390
Percentage of participants with treatment-emergent SAEs		Up to Day 390
Number of participants with clinically significant change from baseline in clinical safety laboratory tests and 12-lead electrocardiogram (ECG)	Clinical safety laboratory tests will include hematology, biochemistry and coagulation.	From Baseline to Day 390
Percentage of participants with clinically significant change from baseline in clinical safety laboratory tests and 12-lead ECG	Clinical safety laboratory tests will include hematology, biochemistry and coagulation.	From Baseline to Day 390
Change from baseline in transferrin saturation (TSAT) (measured at trough)		From Baseline to Day 360
Number of participants with TSAT less than or equal to (<=) 45% (measured at trough)		From Baseline to Day 360
Percentage of participants with TSAT <= 45% (measured at trough)		From Baseline to Day 360
Number of participants with 25% reduction in MRI-based LIC		At Day 180 and 360
Number of participants with 50% reduction in MRI-based LIC		At Day 180 and Day 360
Number of participants with TSAT ≤ 45% or MRI-based LIC < 5 milligrams per gram (mg/g)		At Day 360
Number of participants with TSAT ≤ 45% or MRI-based LIC < 2 mg/g		At Day 360
Change from baseline in joint pain score in a visual analog scale (VAS)	The VAS is a single-item questionnaire. Participants will be asked to record their joint pain at its worst over the previous week, from 0 (No pain) to 10 (Worst possible pain).	From Baseline to Day 360
Change from baseline in modified fatigue impact scale (MFIS) total score	Participants will be asked to read a list of 21 statements and assess how often fatigue has affected them in terms of physical, cognitive, and psychosocial functioning, over the previous 4 weeks, using a 5-point scale from 0 (Never) to 4 (Almost always). The total score is obtained by summing the scores of all the 21 items. Higher scores indicate a greater impact of fatigue on a participant's activities.	From Baseline to Day 360
Change from baseline in health-related quality of life: EuroQoL 5-dimension 5-level instrument (EQ-5D-5L)	The EQ-5D-5L is a standardized measure of health status that provides a simple, generic measure of health for clinical and economic appraisal. Participants will complete the questionnaire based on their health on that day. The EQ-5D-5L descriptive profile includes 5 dimensions: mobility, self-care, usual activities, pain / discomfort, and anxiety / depression. Participants will rate each dimension based on 5 levels of severity: no problems, slight problems, moderate problems, severe problems, and extreme problems. A higher score indicates a more severe outcome than a lower score.	From Baseline to Days 180, 360, and 390
Change from baseline in health-related quality of life: VAS (Arthralgia)	The VAS is a single-item questionnaire. Participants will be asked to record their joint pain at its worst over the previous week, from 0 (No pain) to 10 (Worst possible pain).	From Baseline to Day 180, 360, and 390
Change from baseline in health-related quality of life: Patient global impression of change in clinical status	The PGI - Change (PGI-C) instrument is a self-reported measure that reflects belief about the efficacy of treatment. Participants will be asked to rate the change in their overall symptoms since they started taking investigational product (IP) on a 5-point scale, ranging from 1 (Much improved) to 5 (Much worse). A lower score reflects an improvement in clinical status.	From Baseline to Day 180, 360, and 390
Change from baseline in health-related quality of life: Patient global impression of severity	The PGI - Severity (PGI-S) instrument is a self-reported questionnaire and consists of 1 item that measures disease severity. Participants will be asked to rate the severity of their overall symptoms over the previous week on a 5-point scale from 1 (None) to 5 (Very severe). A higher score reflects a more severe outcome than a lower score.	From Baseline to Day 180, 360, and 390
Change from baseline in health-related quality of life: MFIS physical, cognitive, and psychosocial subscales	Participants will be asked to read a list of 21 statements and assess how often fatigue has affected them in terms of physical, cognitive, and psychosocial functioning, over the previous 4 weeks, using a 5-point scale from 0 (Never) to 4 (Almost always). Items on the MFIS will be aggregated into 3 subscales (Physical, Cognitive, or Psychosocial). Higher scores indicate a greater impact of fatigue on a participant's activities.	From Baseline to Day 180, 360, and 390
Vamifeport plasma concentrations after a single dose		At Day 1
Vamifeport plasma concentrations at steady state		At Days 15, 180, and 360
Change from baseline in total serum iron (measured at trough)		From Baseline to Day 360
Change from baseline in serum ferritin (measured at trough)		From Baseline to Day 360
Frequency of rescue therapy use	For assessment of this outcome measure, data will be collected retrospectively from 1 year before baseline as well as during the study (up to Day 390).	Up to Day 390
Duration of rescue therapy use	For assessment of this outcome measure, data will be collected retrospectively from 1 year before baseline as well as during the study (up to Day 390).	Up to Day 390
Time to first use of rescue therapy		Up to Day 360

Collaborators and Investigators

• Sponsor: CSL Behring

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2026
• Primary Completion (Estimated): March 6, 2028
• Study Completion (Estimated): April 6, 2028

Study Registration Dates

• First Submitted: January 8, 2026
• First Submitted That Met QC Criteria: January 8, 2026
• First Posted (Actual): January 12, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Iron overload; Hereditary hemochromatosis; Small Molecule Ferroportin Inhibitor
• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Iron Metabolism Disorders; Metal Metabolism, Inborn Errors; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Iron Overload; Hemochromatosis
• Other Study ID Numbers: CSL624_2001; 2025-523793-16-00 (Other Identifier: EU CT Number)

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