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.
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).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Oral tablet, daily (or every other day) administration
Royal Adelaide Hospital
Adelaide, South Australia, Australia
Hadassah University Medical Center
Jerusalem, Israel
Galilee Medical Center
Nahariya, Israel
Laniado Hospital - Sanz Medical Center
Netanya, Israel
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
Time frame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
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
Time frame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
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
Time frame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
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
Time frame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
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.
Time frame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
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Shamir Medical Center (Assaf Harofeh Medical Center)
Zrifin, Israel
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
Time frame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
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
Time frame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
Respiratory rate
To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes
Time frame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
Heart rate
To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes
Time frame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
Body temperature
To determine safety and tolerability of KER-047 in participants with functional IDA associated with MDS, MF, and MDS/MPN overlap syndromes
Time frame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
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
Time frame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
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
Time frame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
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
Time frame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
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
Time frame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
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
Time frame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
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
Time frame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
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
Time frame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
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
Time frame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
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
Time frame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
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
Time frame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
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
Time frame: Up to 29 weeks or up to 101 weeks if in the treatment extension
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
Time frame: Week 1 and Week 13 in Part 1 and 2
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
Time frame: Week 1 and Week 13 in Part 1 and 2
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
Time frame: Week 1 and Week 13 in Part 1 and 2
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
Time frame: Week 1 and Week 13 in Part 1 and 2
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
Time frame: Up to 25 weeks
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
Time frame: Up to 25 weeks
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
Time frame: Up to 25 weeks