Iron-Refractory Iron-Deficiency Anemia (IRIDA) MedDRA version: 20.0 Level: PT Classification code 10022972 Term: Iron deficiency anaemia System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Sponsors
Keros Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible for the study if all of the following criteria apply: 1. Male or female > or = 18 years of age, at the time of signing informed consent. 2. Diagnosis of IRIDA based on the following: - Documented homozygous or compound heterozygous TMPRSS6 gene variant(s) of Class 3 or greater (variant of uncertain significance (VUS), likely pathogenic, pathogenic) per the Association for Clinical Genomic Science (ACGS). 3. Serum TSAT at screening or = 4 weeks prior to Day 1, with a maximum of 60 mg/day of oral elemental iron. Intravenous (IV) iron is not permitted during the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: Medical History 1. Body mass index (BMI) >35 kg/m squared 2. Any active infection requiring parenteral antibiotic therapy within 28 days prior to Day 1 or oral antibiotics within 14 days of Day 1. Any infection with >5 days of fever (>38.5 degrees C) within 28 days prior to Day 1. 3. Presence of uncontrolled heart disease or New York Heart Association (NYHA) Class 3 or 4 heart failure. 4. History of uncontrolled hyper- or hypothyroidism. 5. History of drug or alcohol abuse, as defined by the investigator, within the past 2 years. 6. History of stroke, arterial embolism, or unresolved deep venous thrombosis (DVT) within 6 months prior to Day 1. 7. Major surgery within 28 days prior to Day 1. Participants who had surgery more than 28 days prior to Day 1 must have recovered satisfactorily to participate in the study, in the opinion of the Investigator. 8. Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B (HBV), or active infectious hepatitis C (HCV). 9. Any malignancy that has not been in remission and/or has required systemic therapy including radiation, chemotherapy, hormonal therapy, or surgery within the last year prior to Day 1. 10. History of solid organ or hematological transplantation. 11. History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational drug. 12. History of corneal dysplasia. 13. History of any known inflammatory or immunodeficiency disorder (e.g., lupus, common variable immunodeficiency [CVID]). Treatment History 14. Treatment with IV iron within 28 days prior to study entry 15. Receiving treatment with proton pump inhibitors (PPIs). Participants receiving PPIs who discontinue use at least 7 days prior to Day 1 are permitted to enroll. 16. Receiving and plan to continue any disallowed medications listed in the protocol. 17. Treatment with another investigational drug or device, or approved therapy for investigational use = 28 days prior to Day 1, or, if the half-life of the previous product is known, within 5 times the half-life prior to Day 1, whichever is longer. Laboratory Exclusions 18. Hemoglobin level =13.8 g/dL (8.56 mmol/L) (males) or > or = 12.1 g/dL (7.51 mmol/L) (females) 19. Serum ferritin 700 µg/L 20. Absolute lymphocyte count 2x upper limit of normal (ULN) 24. C-reactive protein (CRP) > or =10 mg/L
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Safety assessments will be summarized at Baseline and at each observed time point. Pharmacodynamic and exploratory endpoints will be evaluated as change from baseline after 14 days of treatment in Part 1 and after 28 or 56 days of treatment in Part 2. Pharmacokinetic endpoints will be assessed on Days 8 and 15 in Part 1, and Days 8, 15, 22, and 29 if treatment was 28 days or Days 8, 15, 22, 29, 36, 43, 50, and 57 if treatment was 56 days in Part 2.;Main Objective: To evaluate the safety and tolerability of ascending doses of KER-047 in participants with iron-refractory iron deficiency anemia (IRIDA);Secondary Objective: Secondary Objectives: • To evaluate the pharmacodynamic (PD) effects of KER-047 on iron metabolism in participants with IRIDA • To evaluate plasma accumulation of KER-047 across the treatment period;Primary end point(s): Safety Endpoints - Safety and tolerability as determined by the incidence of adverse events (AEs) and SAEs Pharmacodynamic Endpoints - Hepcidin concentration in plasma - Serum iron - Ferritin - Total iron binding capacity (TIBC) - Transferrin saturation (TSAT) - Reticulocyte hemoglobin content (RET-He/CHr) - Soluble transferrin receptor (sTfR) and sTfR/log ferritin index - TSAT/hepcidin; ferritin/hepcidin Pharmacokinetic Endpoints - mean trough plasma KER-047 concentration (Ctrough) - Plasma KER-047 accumulation (Rac) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Please see above;Timepoint(s) of evaluation of this end point: Please see above | — |
Countries
Netherlands, Spain
Contacts
Public ContactClinical Project Manager
Keros Therapeutics, Inc.
Outcome results
None listed