KER-050 for Anemia in Myelodysplastic Syndromes

Recruiting at55 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Keros Therapeutics

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

Disqualifiers: Active infection, Secondary MDS, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing KER-050, a protein treatment, on patients with low-risk MDS who have low blood cell counts. KER-050 helps the body produce more red blood cells and platelets by blocking signals that slow down their production.

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.

What data supports the effectiveness of the drug KER-050 for treating anemia in myelodysplastic syndromes?

Research on similar drugs like luspatercept, which is used for anemia in myelodysplastic syndromes, shows that targeting certain pathways can help improve anemia. Luspatercept has been effective in achieving transfusion independence in a significant number of patients, suggesting that KER-050 might work similarly. ^{1 2 3 4 5}

What makes the drug KER-050 unique for treating anemia in myelodysplastic syndromes?

KER-050 is unique because it targets the transforming growth factor β pathway, which is different from other treatments like erythropoiesis-stimulating agents or lenalidomide that have limited effectiveness and duration. This novel approach may offer a new option for patients with lower-risk myelodysplastic syndromes who do not respond well to existing therapies. ^{1 4 6 7 8}

Research Team

Eligibility Criteria

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)

Trial Timeline

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

Treatment Details

Interventions

• KER-050 (Erythropoiesis-Stimulating Agent)

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.

Participant Groups

Group I: KER-050 Dose Confirmation Cohort Experimental Treatment 1 Intervention

Participants to receive KER-050 administered subcutaneously every 4 weeks for up to 24 cycles. Eligible participants may be able to continue to receive subcutaneously administered KER-050 after completing 24 cycles.

Group II: KER-050 Cohort 5 Experimental Treatment 1 Intervention

Escalating doses of KER-050 administered subcutaneously every 4 weeks for up to 24 cycles. Eligible participants may be able to continue to receive subcutaneously administered KER-050 after completing 24 cycles.

Group III: KER-050 Cohort 4 Experimental Treatment 1 Intervention

Escalating doses of KER-050 administered subcutaneously every 4 weeks for up to 24 cycles. Eligible participants may be able to continue to receive subcutaneously administered KER-050 after completing 24 cycles.

Group IV: KER-050 Cohort 3 Experimental Treatment 1 Intervention

Escalating doses of KER-050 administered subcutaneously every 4 weeks for up to 24 cycles. Eligible participants may be able to continue to receive subcutaneously administered KER-050 after completing 24 cycles.

Group V: KER-050 Cohort 2 Experimental Treatment 1 Intervention

Escalating doses of KER-050 administered subcutaneously every 4 weeks for up to 4 cycles. Participants have the option to continue to receive KER-050 once 4 cycles have been completed for up to 24 cycles. Eligible participants may be able to continue to receive subcutaneously administered KER-050 after completing 24 cycles.

Group VI: KER-050 Cohort 1 Experimental Treatment 1 Intervention

Escalating doses of KER-050 administered subcutaneously every 4 weeks for up to 4 cycles. Participants have the option to continue to receive KER-050 once 4 cycles have been completed for up to 24 cycles. Eligible participants may be able to continue to receive subcutaneously administered KER-050 after completing 24 cycles.

Who Is Running the Clinical Trial?

Keros Therapeutics

Lead Sponsor

Trials

2

Recruited

260+

Keros Therapeutics, Inc.

Lead Sponsor

Trials

5

Recruited

600+

Findings from Research

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Lenalidomide-Epoetin Alfa Versus Lenalidomide Monotherapy in Myelodysplastic Syndromes Refractory to Recombinant Erythropoietin. [2022]

2. England 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. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Role of Luspatercept in the Management of Lower-Risk Myelodysplastic Syndromes. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. United States pubmed.ncbi.nlm.nih.gov

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

6. Netherlands pubmed.ncbi.nlm.nih.gov

Inhibitors of signaling in myelodysplastic syndrome. [2009]

7. United States pubmed.ncbi.nlm.nih.gov

Lenalidomide in myelodysplastic syndromes: an erythropoiesis-stimulating agent or more? [2021]

8. United States 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. [2022]