Elritercept for Myelodysplastic Syndrome

Recruiting at 27 trial locations

Overseen By Keros Therapeutics, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Keros Therapeutics, Inc.

Must not be taking: Antidepressants, Antipsychotics, others

Disqualifiers: Cardiovascular disease, Stroke, HIV, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 10

225 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, certain treatments like iron chelation, vitamin B12 or folate therapy, androgen use, and high-dose corticosteroids must be stable for a specified period before joining. It's best to discuss your specific medications with the study team.

How does the drug Elritercept differ from other treatments for myelodysplastic syndrome?

Elritercept is unique because it targets the transforming growth factor β (TGF-B) pathway, which is a novel approach in treating myelodysplastic syndromes (MDS). This mechanism is different from traditional treatments like erythropoiesis-stimulating agents and hypomethylating agents, which have limited effectiveness in many patients. ^{1 2 3 4 5}

What is the purpose of this trial?

This study (KER-050-D301) is evaluating the efficacy and safety of elritercept (KER-050) versus placebo in adult participants with transfusion-dependent anemia with very low, low, or intermediate risk MDS, or more recently defined as myelodysplastic neoplasms, with or without ring sideroblasts. The study is divided into the Screening Period, Double-blind Treatment Period, Safety Follow-Up Period and Long-term Follow-up Period. Approximately 255 participants will be enrolled, randomized 2:1 to receive either elritercept or placebo.

Eligibility Criteria

Adults over 18 with very low to intermediate risk Myelodysplastic Syndromes (MDS) and anemia who need regular blood transfusions can join. They must understand the study, have had unsuccessful or intolerant responses to prior treatments like ESAs, and agree to use contraception. Those with more than 5% bone marrow blasts or poor physical condition cannot participate.

Inclusion Criteria

I am able to get out of my bed or chair and move around.

I agree to use effective birth control methods if I can have children or am a sexually active male.

My latest bone marrow test shows less than 5% immature cells.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment - Primary Phase

Participants receive either KER-050 or placebo subcutaneously every 4 weeks

24 weeks

Study visits every 2 weeks from Cycle 1 through Cycle 6 and every 4 weeks from Cycle 7

Double-blind Treatment - Secondary Phase

Continuation of double-blind treatment for participants who meet criteria after the Primary Phase

24 weeks

Study visits every 4 weeks

Double-blind Treatment - Extension Phase

Eligible participants continue receiving the same double-blind treatment until study unblinding or individual discontinuation

Variable, based on individual criteria

Safety Follow-up

Participants are monitored for safety after the last dose of study treatment

8 weeks

Study visits every 4 weeks

Long-term Follow-up

Quarterly follow-up for up to 5 years from the first dose or 3 years after the last dose

Up to 5 years

Treatment Details

Interventions

• Elritercept

Trial Overview The trial is testing Elritercept (KER-050) against a placebo in adults with MDS-related anemia requiring transfusions. Participants are randomly assigned in a 2:1 ratio to receive either the drug or placebo during various phases including treatment and follow-up periods.

Participant Groups

Group I: Experimental: KER-050 (N=150) Experimental Treatment 1 Intervention

KER-050 will be administered subcutaneously every 4 weeks. The Primary Phase of the Double-Blind Treatment Period will last 24 weeks. Based on the outcome of the MDS Disease Assessment approximately 24 calendar weeks after Cycle 1 Day 1, participants will either continue in the Secondary Phase or be discontinued from treatment. During the Secondary Phase of the Double-Blind Treatment Period, all participants will continue to receive the same double-blind treatment they received during the Primary Phase, which will last 24 weeks. The second MDS Disease Assessment should be completed approximately 48 calendar weeks after C1D1 to determine whether the participant will enter the Extension Phase or be discontinued from treatment. During the Extension Phase of the Double-Blind Treatment Period, all participants will continue to receive the same double-blind treatment that they received during the Primary and Secondary Phases.

Group II: Placebo Comparator (N=70) Placebo Group 1 Intervention

Placebo will be administered subcutaneously every 4 weeks. The Primary Phase of the Double-Blind Treatment Period will last 24 weeks. Based on the outcome of the MDS Disease Assessment approximately 24 calendar weeks after Cycle 1 Day 1, participants will either continue in the Secondary Phase or be discontinued from treatment. During the Secondary Phase of the Double-Blind Treatment Period, all participants will continue to receive the same double-blind treatment they received during the Primary Phase, which will last 24 weeks. The second MDS Disease Assessment should be completed approximately 48 calendar weeks after C1D1 to determine whether the participant will enter the Extension Phase or be discontinued from treatment. During the Extension Phase of the Double-Blind Treatment Period, all participants will continue to receive the same double-blind treatment that they received during the Primary and Secondary Phases.

Who Is Running the Clinical Trial?

Keros Therapeutics, Inc.

Lead Sponsor

Trials

5

Recruited

600+

PSI CRO

Industry Sponsor

Trials

13

Recruited

2,800+

Findings from Research

There have been no new drug approvals for myelodysplastic syndromes (MDS) in 13 years, highlighting a significant gap in treatment advancements since decitabine was approved in 2006.

Emerging therapies like luspatercept and imetelstat show promise for treating symptomatic anemia in lower-risk MDS patients, and future treatments are expected to be more personalized based on genetic and biomarker analyses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving therapies for lower-risk myelodysplastic syndromes. Bewersdorf, JP., Zeidan, AM.[2020]

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]

Several new therapeutic agents are being developed for myelodysplastic syndromes (MDS), including clofarabine, ezatiostat, tipifarnib, laromustine, and histone deacetylase inhibitors, each with different mechanisms of action.

Despite the challenges of MDS, which often leads to complications within 3 to 5 years of diagnosis, the ongoing clinical trials suggest that new treatment options may become available in the next 5 to 10 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel therapies for myelodysplastic syndromes. Steensma, DP.[2018]

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]

The TGF-B pathway is overactive in lower-risk myelodysplastic syndromes (MDS), leading to myelosuppression and contributing to anemia, which is a key treatment target.

Novel agents like luspatercept and sotatercept, which act as ligand traps for activin receptors, have shown early promise in treating anemia in MDS, particularly in patients with specific mutations, suggesting a new approach to therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activin Receptor II Ligand Traps: New Treatment Paradigm for Low-Risk MDS. Komrokji, RS.[2020]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Evolving therapies for lower-risk myelodysplastic syndromes. [2020]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Inhibitors of signaling in myelodysplastic syndrome. [2009]

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

Novel therapies for myelodysplastic syndromes. [2018]

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

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

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

Activin Receptor II Ligand Traps: New Treatment Paradigm for Low-Risk MDS. [2020]