Clinical trial NCT05927012: 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).
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Iron Deficiency Anemia
Keywords: Functional Iron Deficiency Anemia (Functional IDA)
Myelodysplastic Syndromes (MDS)
Myelofibrosis (MF)
Myelodysplastic Syndrome (MDS)
Myeloproliferative Neoplasm Overlap Syndromes (MPN)
Lead sponsor: Keros Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2023-07-03
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 2 parts: Part 1 Initial Titration Strategy and Part 2 Cohort Expansion or Alternate Titration Strategy
Primary purpose: TREATMENT

Brief 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.

Detailed 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of participants experiencing Treatment-emergent adverse events (TEAEs)
timeFrame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
measure: Dose limiting toxicities (DLTs)
timeFrame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
measure: Percentage of participants experiencing Treatment-related AEs (Adverse events)
timeFrame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
measure: Number of participants discontinuing due to AEs (Adverse events)
timeFrame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
measure: Change from Baseline in clinical laboratory values
timeFrame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
measure: Systolic Blood Pressure
timeFrame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
measure: Diastolic Blood Pressure
timeFrame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
measure: Respiratory rate
timeFrame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
measure: Heart rate
timeFrame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
measure: Body temperature
timeFrame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
measure: Fridericia corrected QT interval via 12-lead Electrocardiogram (ECG)
timeFrame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
measure: QT interval via 12-lead Electrocardiogram (ECG)
timeFrame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
measure: QRS interval via 12-lead Electrocardiogram (ECG)
timeFrame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
measure: PR interval via 12-lead Electrocardiogram (ECG)
timeFrame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
measure: Body weight (in kg)
timeFrame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
Secondary outcomes:
measure: Change from baseline in reticulocyte hemoglobin content (RET-He)
timeFrame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
measure: Change from baseline in hepcidin concentration
timeFrame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
measure: Change from baseline in hemoglobin (Hgb)
timeFrame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
measure: Proportion of participants who have Hgb increase of ≥1.0 g/dL (0.6 mmol/L)
timeFrame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
measure: Proportion of participants who have Hgb increase of ≥1.5 g/dL (0.9 mmol/L)
timeFrame: Up to 29 weeks in Part 1 or up to 101 weeks if continuing in the treatment extension
measure: Proportion of RBC-transfused participants who achieve ≥8 weeks of transfusion independence during any consecutive period up to End of Treatment
timeFrame: Up to 29 weeks or up to 101 weeks if in the treatment extension
measure: Plasma KER-047 and any metabolites concentration, summarized by time point
timeFrame: Week 1 and Week 13 in Part 1 and 2
measure: Estimated peak plasma concentration (Cmax)
timeFrame: Week 1 and Week 13 in Part 1 and 2
measure: Time to peak plasma concentration (Tmax)
timeFrame: Week 1 and Week 13 in Part 1 and 2
measure: Area under the plasma KER-047 concentration curve (AUClast)
timeFrame: Week 1 and Week 13 in Part 1 and 2
measure: Mean trough (Ctrough) plasma KER-047 and metabolites of interest concentration
timeFrame: Up to 25 weeks
measure: Plasma KER-047 and metabolites of interest accumulation (Rac)
timeFrame: Up to 25 weeks
measure: Determination of steady-state (as appropriate)
timeFrame: Up to 25 weeks
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Jerusalem
country: Israel
facility: Hadassah University Medical Center
city: Nahariya
country: Israel
facility: Galilee Medical Center
city: Netanya
country: Israel
facility: Laniado Hospital - Sanz Medical Center
city: Zrifin
country: Israel
facility: Shamir Medical Center (Assaf Harofeh Medical Center)
Study officials:
References: