A Study to Evaluate the Safety and Preliminary Efficacy of a Response-guided Dose Titration of KER-047 in the Treatment of Functional IDA (Iron Deficiency Anemia).

Iron Deficiency Anemia Clinical Trial

Official title:

A Phase 2, Intrapatient Dose Titration Study of KER-047 in Participants With Functional Iron Deficiency Anemia Associated With Myelodysplastic Syndromes, Myelofibrosis, and Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05927012
• Other study ID #: KER047-IR-202
• Status: Withdrawn
• Phase: Phase 2
• Start date: November 30, 2023
• Est. completion date: January 4, 2026

Study information

• Verified date: November 2023
• Source: Keros Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to explore the safety and preliminary efficacy of a response-guided dose titration of KER-047 in the treatment of functional IDA (Iron deficiency anemia) in MDS (Myelodysplastic syndrome), MF(Myelofibrosis), and MDS/MPN (Myeloproliferative neoplasm) overlap syndromes.

Description:

This is a Phase 2 multicenter, open-label study being conducted to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of response-guided dose titration of KER-047 in adult participants with functional iron deficiency anemia (IDA) associated with myelodysplastic syndrome (MDS), myelofibrosis (MF), and myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap syndromes. Approximately 20 patients will be enrolled. Dosing of KER-047 may be adjusted based on safety/tolerability and treatment response. The study will be conducted in 2 parts: Part 1 Initial Titration Strategy and Part 2 Cohort Expansion or Alternate Titration Strategy. The total planned duration of participation for an individual participant is approximately 32 weeks (4-week screening phase, 24-week treatment period, and 4-week follow-up period). For participants in the extension phase, the maximum duration of participation would be approximately 104 weeks (2 years) (4-week screening phase, 24-week treatment period, 18 month [72 weeks] extension period, and 4-week follow-up period).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 4, 2026
• Est. primary completion date: August 29, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female =18 years of age, at the time of signing informed consent.
• One of the following:

1. Diagnosis of MDS according to the 2016 World Health Organization (WHO) classification that meets Revised International Prognostic Scoring System (IPSS-R) classification of very low, low, or intermediate risk disease with bone marrow blast percentage <5% within 6 months prior to Day 1 (D1).

2. Diagnosis of primary myelofibrosis, post polycythemia vera MF, or post-essential thrombocytopenia MF according to the 2017 WHO criteria with bone marrow and peripheral blood blast percentage <2%, or stable between 2% to 5% over 6 months.

3. Diagnosis of MDS/MPN overlap syndromes according to the 2016 WHO classification, with bone marrow blast percentage <5% within 6 months prior to D1.

• Anemia with iron-restricted erythropoiesis as assessed by laboratory criteria during screening.
• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information in accordance with national and local study participant privacy regulations.
• Females of childbearing potential and sexually active males must meet the contraception requirements as outlined in the protocol.

Exclusion Criteria:

• Active infection within 14 days of D1.
• IPSS-R score indicating high or very high risk MDS, accelerated myelofibrosis (defined as >10% blasts), or diagnosis of acute leukemia.
• Diagnosis of hemolytic anemia.
• Diagnosis of porphyria.
• Anemia due to blood loss 28 days prior to D1.
• Diagnosis of thalassemia, thalassemia trait, or other hemoglobinopathy.
• History of drug or alcohol abuse, as defined by the Investigator, within the past 2 years.
• History of stroke, arterial embolism, or deep venous thrombosis within 6 months prior to D1.
• Known positive for human immunodeficiency virus, active infectious hepatitis B virus or active infectious hepatitis C virus.

Related Conditions & MeSH terms

• Anemia
• Anemia, Iron-Deficiency
• Deficiency Diseases
• Iron Deficiency Anemia
• Myelodysplastic Syndromes

Intervention

Drug:
• KER-047
Oral tablet, daily (or every other day) administration

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Israel	Hadassah University Medical Center	Jerusalem
Israel	Galilee Medical Center	Nahariya
Israel	Laniado Hospital - Sanz Medical Center	Netanya
Israel	Shamir Medical Center (Assaf Harofeh Medical Center)	Zrifin

Sponsors (1)

Lead Sponsor	Collaborator
Keros Therapeutics, Inc.

Countries where clinical trial is conducted

Australia,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants experiencing Treatment-emergent adverse events (TEAEs)	To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
Primary	Dose limiting toxicities (DLTs)	To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
Primary	Percentage of participants experiencing Treatment-related AEs (Adverse events)	To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
Primary	Number of participants discontinuing due to AEs (Adverse events)	To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
Primary	Change from Baseline in clinical laboratory values	To determine the safety and tolerability based on changes from baseline in select clinical laboratory parameters including: Alkaline phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, Glucose, Potassium, Sodium, Total bilirubin, Folate, WBC count, Platelet Count, Reticulocyte Count, Transferrin Saturation percentage.; Note - Select safety parameters will be listed as separate outcomes during results update.	Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
Primary	Systolic Blood Pressure	To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
Primary	Diastolic Blood Pressure	To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
Primary	Respiratory rate	To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
Primary	Heart rate	To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
Primary	Body temperature	To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
Primary	Fridericia corrected QT interval via 12-lead Electrocardiogram (ECG)	To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
Primary	QT interval via 12-lead Electrocardiogram (ECG)	To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
Primary	QRS interval via 12-lead Electrocardiogram (ECG)	To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
Primary	PR interval via 12-lead Electrocardiogram (ECG)	To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
Primary	Body weight (in kg)	To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
Secondary	Change from baseline in reticulocyte hemoglobin content (RET-He)	To evaluate the Pharmacodynamic (PD) effects of KER-047 on iron metabolism in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
Secondary	Change from baseline in hepcidin concentration	To evaluate the Pharmacodynamic (PD) effects of KER-047 on iron metabolism in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
Secondary	Change from baseline in hemoglobin (Hgb)	To evaluate the effect of KER-047 on anemia in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
Secondary	Proportion of participants who have Hgb increase of =1.0 g/dL (0.6 mmol/L)	To evaluate the effect of KER-047 on anemia in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
Secondary	Proportion of participants who have Hgb increase of =1.5 g/dL (0.9 mmol/L)	To evaluate the effect of KER-047 on anemia in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
Secondary	Proportion of RBC-transfused participants who achieve =8 weeks of transfusion independence during any consecutive period up to End of Treatment	To evaluate the effect of KER-047 on anemia in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Up to 29 weeks or up to 101 weeks if in the treatment extension
Secondary	Plasma KER-047 and any metabolites concentration, summarized by time point	To evaluate the Pharmacokinetic (PK) of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Week 1 and Week 13 in Part 1 and 2
Secondary	Estimated peak plasma concentration (Cmax)	To evaluate the Pharmacokinetic (PK) of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Week 1 and Week 13 in Part 1 and 2
Secondary	Time to peak plasma concentration (Tmax)	To evaluate the Pharmacokinetic (PK) of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Week 1 and Week 13 in Part 1 and 2
Secondary	Area under the plasma KER-047 concentration curve (AUClast)	To evaluate the Pharmacokinetic (PK) of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Week 1 and Week 13 in Part 1 and 2
Secondary	Mean trough (Ctrough) plasma KER-047 and metabolites of interest concentration	To evaluate the Pharmacokinetic (PK) of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Up to 25 weeks
Secondary	Plasma KER-047 and metabolites of interest accumulation (Rac)	To evaluate the Pharmacokinetic (PK) of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Up to 25 weeks
Secondary	Determination of steady-state (as appropriate)	To evaluate the Pharmacokinetic (PK) of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes	Up to 25 weeks