KER-050 for Anemia in Myelodysplastic Syndromes

Recruiting at 67 trial locations

Overseen By Clinical Study Team

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Keros Therapeutics

Must not be taking: Antibiotics, ESAs, G-CSF, others

Disqualifiers: Active infection, Secondary MDS, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 96 weeks

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called KER-050 to determine its effectiveness for anemia in individuals with specific types of myelodysplastic syndromes (MDS), a condition where the bone marrow fails to produce enough healthy blood cells. Participants will receive varying doses of KER-050 to assess its efficacy and safety. The study seeks individuals with very low, low, or intermediate risk MDS who experience anemia, indicated by lower-than-normal red blood cell levels. Those who have not recently used treatments like erythropoiesis stimulating agents may be suitable candidates. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires that you stop certain medications before starting. You must not have taken erythropoiesis stimulating agents, certain growth factors, or iron chelation therapy within specific time frames before the trial begins.

Is there any evidence suggesting that KER-050 is likely to be safe for humans?

Research shows that KER-050 is generally well-tolerated by patients. Studies have demonstrated that participants taking KER-050 experienced improved blood cell counts, a positive outcome. Importantly, extended use of KER-050 proved safe for most individuals, with no major safety issues reported. This suggests that KER-050 could be a safe option for treating anemia in people with Myelodysplastic Syndromes (MDS), a condition where blood cells do not develop properly. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for anemia in MDS?

Researchers are excited about KER-050 for anemia in myelodysplastic syndromes because it offers a novel approach compared to existing treatments like erythropoiesis-stimulating agents (ESAs) and blood transfusions. Unlike these standard options, KER-050 works by targeting and modulating the TGF-beta signaling pathway, which is crucial in regulating red blood cell production. This unique mechanism has the potential to not only boost red blood cell counts but also improve overall bone marrow function. Furthermore, KER-050 is administered subcutaneously, providing a convenient method for patients and potentially reducing the need for frequent hospital visits associated with transfusions.

What evidence suggests that KER-050 could be an effective treatment for anemia in myelodysplastic syndromes?

Research has shown that KER-050, the investigational treatment in this trial, may help treat anemia in people with myelodysplastic syndromes (MDS). Studies have found that KER-050 can reduce the need for blood transfusions over time. It is generally well-tolerated, and extended use might improve blood health and further decrease transfusion requirements. Patients with lower-risk MDS have experienced benefits from KER-050, such as better management of anemia and iron levels. This suggests that KER-050 could be effective for those with very low, low, or intermediate-risk MDS. ^{1 2 4 5 6}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

This trial is for patients with very low to intermediate risk Myelodysplastic Syndromes (MDS) who have anemia. They should not have had recent infections, vitamin deficiencies, or certain treatments like chemotherapy. Participants need a specific white blood cell count and bone marrow blast percentage, and must agree to use contraception if applicable.

Inclusion Criteria

< 5% blasts in bone marrow

I agree to use effective birth control methods.

I can care for myself, but my anemia affects my daily activities.

Exclusion Criteria

Pregnant or lactating females

Platelet count > 450 x 10*9/L or < 30 x 10*9/L

Vitamin B12 < 148 pmol/L (< 200 pg/mL)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive escalating doses of KER-050 administered subcutaneously every 4 weeks for up to 24 cycles

96 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Open-label extension (optional)

Eligible participants may continue to receive KER-050 after completing 24 cycles

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• KER-050

Trial Overview The study tests KER-050's effectiveness on anemia in MDS patients at various risk levels. It aims to see how well the drug improves red blood cell counts without transfusions or if it reduces the need for them in those already receiving transfusions.

How Is the Trial Designed?

Group I: Part 2: Elritercept Dose Confirmation Cohort G Experimental Treatment 1 Intervention

Participants with MDS (either RS-positive or non-RS) who require RBC transfusions and have either relapsed, become refractory to, or intolerant to frontline luspatercept treatment will be administered Elritercept at 3.75 mg/kg, SC injection, on Day 1, every 4 weeks for up to 24 cycles (each cycle = 28 days). The dose can be modified based on participant's response.

Group II: Part 2: Elritercept Dose Confirmation Cohort F Experimental Treatment 1 Intervention

Participants with MDS (either RS-positive or non-RS) who are requiring RBC transfusions, have iron-overload, and are not receiving iron chelation therapy will be administered Elritercept at 3.75 mg/kg, SC injection, on Day 1, every 4 weeks for up to 24 cycles (each cycle = 28 days). The dose can be modified based on participant's response.

Group III: Part 2: Elritercept Dose Confirmation Cohort E Experimental Treatment 1 Intervention

Participants with MDS (either RS-positive or non-RS) who are requiring RBC transfusions, have iron-overload, and are receiving iron chelation therapy will be administered Elritercept at 3.75 mg/kg, SC injection, on Day 1, every 4 weeks for up to 24 cycles (each cycle = 28 days). The dose can be modified based on participant's response.

Group IV: Part 2: Elritercept Dose Confirmation Cohort C Experimental Treatment 1 Intervention

Participants who are non-transfused with either RS-positive MDS or non-RS MDS will be administered Elritercept at 3.75 mg/kg, SC injection, on Day 1, every 4 weeks for up to 24 cycles (each cycle = 28 days). The dose can be modified based on participant's response.

Group V: Part 2: Elritercept Dose Confirmation Cohort B Experimental Treatment 1 Intervention

Participants with non-RS MDS who are requiring RBC transfusions will be administered Elritercept at 3.75 mg/kg, SC injection, on Day 1, every 4 weeks for up to 24 cycles (each cycle = 28 days). The dose can be modified based on participant's response.

Group VI: Part 2: Elritercept Dose Confirmation Cohort A Experimental Treatment 1 Intervention

Participants with ring sideroblasts (RS)-positive Myelodysplastic syndrome (MDS) who are requiring red blood cell (RBC) transfusions will be administered Elritercept at 3.75 mg/kg, SC injection, on Day 1, every 4 weeks for up to 24 cycles (each cycle = 28 days). The dose can be modified based on participant's response.

Group VII: Part 1: Elritercept Cohort 5 Experimental Treatment 1 Intervention

Participants will be administered elritercept at 5.0 mg/kg, SC injection, every 4 weeks on Day 1 of each cycle for up to 4 cycles (each cycle = 28 days). Following the above dose regimen, participants will continue to receive elritercept, administered SC, on Day 1, every 4 weeks up to 24 cycles(each cycle = 28 days).

Group VIII: Part 1: Elritercept Cohort 4 Experimental Treatment 1 Intervention

Participants will be administered elritercept at 3.75 mg/kg, SC injection, every 4 weeks on Day 1 of each cycle for up to 4 cycles (each cycle = 28 days). Following the above dose regimen, participants will continue to receive elritercept, administered SC, on Day 1, every 4 weeks up to 24 cycles (each cycle = 28 days).

Group IX: Part 1: Elritercept Cohort 3 Experimental Treatment 1 Intervention

Participants will be administered elritercept at 2.5 mg/kg, SC injection, every 4 weeks on Day 1 of each cycle for up to 4 cycles (each cycle = 28 days). Following the above dose regimen, participants will continue to receive elritercept, administered SC, on Day 1, every 4 weeks up to 24 cycles (each cycle = 28 days).

Group X: Part 1: Elritercept Cohort 2 Experimental Treatment 1 Intervention

Participants will be administered elritercept at 1.5 mg/kg, SC injection, every 4 weeks on Day 1 of each cycle for up to 4 cycles (each cycle = 28 days). Following the above dose regimen, participants will continue to receive elritercept, administered SC, on Day 1, every 4 weeks up to 24 cycles (each cycle = 28 days).

Group XI: Part 1: Elritercept Cohort 1 Experimental Treatment 1 Intervention

Participants will be administered elritercept at 0.75 milligrams per kilogram (mg/kg), subcutaneous (SC) injection, every 4 weeks on Day 1 of each cycle for up to 4 cycles (each cycle = 28 days). Following the above dose regimen, participants will continue to receive elritercept, administered SC, on Day 1, every 4 weeks up to 24 cycles (each cycle = 28 days).

Group XII: Long-term Extension Cohort Experimental Treatment 1 Intervention

Participants from Part 1 and 2 cohorts who may have potential benefit from continued elritercept treatment, in the opinion of the Investigator, may elect to continue in the LTE at the same dose they were being administered in Part 1 and 2, SC injection, on day 1, every 4 weeks until end of treatment (EOT) (approximately 122 months).

Group XIII: Experimental: Part 2: Elritercept Dose Confirmation Cohort D Experimental Treatment 1 Intervention

Participants with chronic myelomonocytic leukemia (CMML) and anemia will be administered Elritercept at 3.75 mg/kg, SC injection, on Day 1, every 4 weeks for up to 24 cycles (each cycle = 28 days). The dose can be modified based on participant's response.

Who Is Running the Clinical Trial?

Keros Therapeutics

Lead Sponsor

Trials

2

Recruited

260+

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Keros Therapeutics, Inc.

Lead Sponsor

Trials

5

Recruited

600+

Published Research Related to This Trial

Luspatercept has been approved for treating lower-risk myelodysplastic syndromes (LR-MDS) with specific mutations, showing promise in reducing anemia and potentially replacing erythropoiesis-stimulating agents as a first-line treatment.

Current therapies for LR-MDS, including ESAs and hypomethylating agents, are effective in less than 50% of patients, highlighting the need for new treatments targeting different biological pathways to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next-generation therapy for lower-risk MDS. Sébert, M.[2023]

Erythropoiesis-stimulating agents (ESAs) like erythropoietin are commonly used as first-line treatments for lower-risk myelodysplastic syndromes (MDS), showing favorable responses in about 50% of patients, although these responses can be short-lived.

New treatments like sotatercept and luspatercept, which inhibit the transforming growth factor (TGF)-β superfamily, offer a promising alternative by stimulating erythroid differentiation and potentially alleviating anemia in patients who do not respond to ESAs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increasing the effectiveness of hematopoiesis in myelodysplastic syndromes: erythropoiesis-stimulating agents and transforming growth factor-β superfamily inhibitors. Mies, A., Platzbecker, U.[2018]

Recent research has identified new molecular therapeutic targets for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), leading to the development of promising new drug classes such as farnesyltransferase inhibitors and receptor tyrosine kinase inhibitors.

Early clinical trials suggest these new drugs may change the standard treatment for MDS, focusing on resolving blood cell deficiencies and targeting the disease's specific mechanisms, although most studies are still in the early stages of development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibitors of signaling in myelodysplastic syndrome. Gore, SD.[2009]

Lenalidomide is an effective treatment for transfusion-dependent anemia in lower-risk myelodysplastic syndromes (MDS), particularly in patients with the deletion 5q chromosomal abnormality, but it also shows clinical activity in those without this specific abnormality.

The use of lenalidomide in MDS exemplifies reciprocal translational research, where laboratory findings informed clinical applications, enhancing our understanding of both the drug's mechanisms of action and the biology of MDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in myelodysplastic syndromes: an erythropoiesis-stimulating agent or more? Komrokji, RS., Lancet, JE., List, AF.[2021]

In a phase III study involving 239 patients with lower-risk non-del(5q) myelodysplastic syndromes, lenalidomide led to a significant rate of red blood cell (RBC) transfusion independence (26.9%) compared to only 2.5% in the placebo group, indicating its efficacy in this patient population.

Lenalidomide treatment was associated with improvements in health-related quality of life (HRQoL) for those achieving RBC transfusion independence, and the safety profile was consistent with known effects, primarily involving neutropenia and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase III Study of Lenalidomide Versus Placebo in RBC Transfusion-Dependent Patients With Lower-Risk Non-del(5q) Myelodysplastic Syndromes and Ineligible for or Refractory to Erythropoiesis-Stimulating Agents. Santini, V., Almeida, A., Giagounidis, A., et al.[2022]

Luspatercept is a newly approved treatment for anemia in patients with lower-risk myelodysplastic syndromes (LR-MDS), showing significant efficacy in a phase III trial where 38% of patients achieved transfusion independence compared to only 13% in the placebo group.

The treatment has a favorable safety profile, with common side effects like fatigue and dizziness occurring more frequently in the initial treatment cycles but decreasing over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of Luspatercept in the Management of Lower-Risk Myelodysplastic Syndromes. Tinsley-Vance, SM., Davis, M., Ajayi, O.[2023]

In a phase III trial with 195 patients suffering from lower-risk, non-del(5q) myelodysplastic syndromes (MDS), the combination of lenalidomide (LEN) and epoetin (EPO) alfa resulted in a significantly higher major erythroid response (28.3%) compared to LEN alone (11.5%).

The combination treatment not only increased the response rate but also provided a longer duration of response, with a median major erythroid response duration of 23.8 months for the LEN-EPO group compared to 13 months for LEN alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide-Epoetin Alfa Versus Lenalidomide Monotherapy in Myelodysplastic Syndromes Refractory to Recombinant Erythropoietin. List, AF., Sun, Z., Verma, A., et al.[2022]

Sotatercept, a novel treatment for anemia in patients with lower-risk myelodysplastic syndromes, demonstrated a 49% overall rate of hematological improvement, indicating its efficacy in patients who had previously failed erythropoiesis-stimulating agents.

The treatment was generally well tolerated, with common side effects including fatigue and peripheral edema, and only a small percentage of patients experiencing severe adverse events, suggesting a favorable safety profile for sotatercept.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotatercept with long-term extension for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes: a phase 2, dose-ranging trial. Komrokji, R., Garcia-Manero, G., Ades, L., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06499285

The Efficacy and Safety of Elritercept in Adult Participants ... This is a Phase 3, double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of KER-050 versus placebo. KER-050 an investigational ...

2. ir.kerostx.com ir.kerostx.com/news-releases/news-release-details/keros-therapeutics-presents-clinical-data-its-elritercept

Keros Therapeutics Presents Clinical Data from its Elritercept ... Elritercept demonstrated a durable transfusion independence in lower-risk myelodysplastic syndromes, including in patients with high ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10428326/

S166: KER-050 TREATMENT IMPROVED MARKERS OF ... KER-050 was generally well-tolerated with longer-term treatment and has the potential to drive hematological improvement and reduce transfusion burden.

4. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/196/500043/Durable-Clinical-Benefit-with-Ker-050-Treatment

Durable Clinical Benefit with Ker-050 Treatment: Findings ... Durable clinical benefit with Ker-050 treatment: findings from an ongoing Phase 2 study in participants with lower-risk MDS.

5. healthtree.org healthtree.org/mds/community/articles/how-effective-is-elritercept-low-risk-mds-patients

How Effective Is Elritercept for Low-risk MDS? Elritercept (KER-050, Keros Therapeutics) is a medicine for low—to intermediate-risk MDS patients that helps improve anemia and iron overload.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04419649

NCT04419649 | A Study of KER-050 to Treat Anemia Due ... It is being developed for the treatment of low blood cell counts, or cytopenias including anemia and thrombocytopenia in patients with Myelodysplastic Syndrome ...