Homeostatic Iron Regulator Gene-related Hereditary Hemochromatosis
Conditions
Keywords
Small Molecule Ferroportin Inhibitor, Hereditary hemochromatosis, Iron overload
Brief summary
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.
Interventions
DRUGVamifeport
Vamifeport capsule administered orally.
DRUGPlacebo
Placebo capsule matching IP administered orally.
Sponsors
CSL Behring
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
This is multicenter, randomized, placebo-controlled double-blind, parallel-group study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 2.4 and 16 mg/g (43.0 and 286.5 mmol/kg) dry weight (dw) at Screening. * Body mass index between 18.5 and 34.9 kilograms per meter squared (kg/m\^2).
Exclusion criteria
* Clinically relevant laboratory abnormalities, 12-lead electrocardiogram (ECG) findings, or medical history.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in magnetic resonance imaging (MRI)-based liver iron concentration (LIC) | At Baseline and Day 360 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | From Baseline to Day 390 | Clinical safety laboratory tests will include hematology, biochemistry and coagulation. |
| Percentage of participants with clinically significant change from baseline in clinical safety laboratory tests and 12-lead ECG | From Baseline to Day 390 | Clinical safety laboratory tests will include hematology, biochemistry and coagulation. |
| 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) | From Baseline to Day 360 | 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). |
| Change from baseline in modified fatigue impact scale (MFIS) total score | From Baseline to Day 360 | 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. |
| Change from baseline in health-related quality of life: EuroQoL 5-dimension 5-level instrument (EQ-5D-5L) | From Baseline to Days 180, 360, and 390 | 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. |
| Change from baseline in health-related quality of life: VAS (Arthralgia) | From Baseline to Day 180, 360, and 390 | 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). |
| Change from baseline in health-related quality of life: Patient global impression of change in clinical status | From Baseline to Day 180, 360, and 390 | 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. |
| Change from baseline in health-related quality of life: Patient global impression of severity | From Baseline to Day 180, 360, and 390 | 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. |
| Change from baseline in health-related quality of life: MFIS physical, cognitive, and psychosocial subscales | From Baseline to Day 180, 360, and 390 | 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. |
| 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 | Up to Day 390 | 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). |
| Duration of rescue therapy use | Up to Day 390 | 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). |
| Time to first use of rescue therapy | Up to Day 360 | — |
Countries
Australia, Austria, Belgium, Canada, Czechia, Denmark, France, Germany, Ireland, Italy, Netherlands, New Zealand, Poland, Romania, Spain, Switzerland, United Kingdom, United States
Contacts
CONTACTTrial Registration Coordinator
Outcome results
None listed