KER-050 for Myelofibrosis

Recruiting at 58 trial locations

Overseen By Clinical Study Team

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Takeda

Must be taking: Ruxolitinib

Must not be taking: TGF-β inhibitors, IMiDs

Disqualifiers: Active infection, Cardiac conditions, Obesity, 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: 13

Duration: 52 weeks

135 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 for myelofibrosis, a bone marrow disorder that causes severe anemia and other blood-related issues. Researchers aim to determine if KER-050 is safe and effective when used alone or with ruxolitinib, a common JAK inhibitor. People living with myelofibrosis who have ongoing anemia despite previous treatments might be suitable for this study. Participants will receive either KER-050 alone or in combination with ruxolitinib to evaluate different treatment approaches. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop all current medications, but if you are taking a JAK inhibitor, you must have stopped it at least 8 weeks before starting the trial. If you are on ruxolitinib, you need to have been on a stable dose for at least 4 weeks before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that KER-050 has been generally well-tolerated in earlier studies. In one study with 41 participants, those who received at least one dose of KER-050 reported no major safety issues. This suggests it might be safe to use, though, as with any treatment, some side effects may occur.

When combined with ruxolitinib, data indicates that this combination is manageable. Ruxolitinib, already approved by the FDA for other uses, supports its safety. The goal of combining it with KER-050 is to address the anemia (low red blood cell count) often seen in patients with myelofibrosis.

The treatment is currently in Phase 2 trials, meaning researchers are still testing it for safety and effectiveness. However, early results appear promising for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatment options for myelofibrosis, which often rely on JAK inhibitors like ruxolitinib to manage symptoms, KER-050 offers a fresh approach. KER-050 is unique as it is a subcutaneous injection designed to address ineffective blood cell production, potentially improving anemia and other blood-related issues. Researchers are excited because KER-050 could offer benefits not only as a standalone therapy but also when combined with ruxolitinib, possibly enhancing overall treatment effectiveness and patient outcomes.

What evidence suggests that this trial's treatments could be effective for Myelofibrosis?

Research shows that KER-050 is designed to block certain proteins that disrupt blood cell production. Previous patients experienced significant improvements in fatigue, often early in their treatment. Studies have also shown that KER-050 can help reduce the need for blood transfusions, especially in patients who require them frequently. In this trial, some participants will receive KER-050 alone, while others will receive it with ruxolitinib. When combined with ruxolitinib, KER-050 may help shrink the spleen and improve overall symptoms in myelofibrosis. This combination might also help manage ruxolitinib's side effects, such as low blood cell counts. These findings suggest that KER-050, alone or with ruxolitinib, could effectively treat myelofibrosis. ^{2 6 7 8 9}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Myelofibrosis, specifically those previously treated with JAK inhibitors or ineligible for them. Participants must have anemia or require red blood cell transfusions and should be on a stable dose of ruxolitinib for at least 4 weeks if they're already receiving it.

Inclusion Criteria

Life expectancy ≥12 months per Investigator assessment

In the opinion of the Investigator, the participant is able and willing to comply with the requirements of the protocol (e.g., all study procedures, return for follow-up visits)

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

Exclusion Criteria

I haven't needed IV antibiotics in the last 28 days or oral antibiotics in the last 14 days.

I do not have major health issues that would prevent me from joining the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive KER-050 as monotherapy or in combination with ruxolitinib, administered every 4 weeks

52 weeks

13 visits (in-person, every 4 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• KER-050
• Ruxolitinib

Trial Overview

The study is testing KER-050 alone and in combination with ruxolitinib to see how safe and effective these treatments are for Myelofibrosis. It's a Phase 2 trial, which means it's looking at the treatment's effectiveness while continuing to ensure safety.

How Is the Trial Designed?

Group I: Long-Term Extension Experimental Treatment 2 Interventions

Participants from Arms 1A, 1B, 2A, 2B and 2C benefiting from the continued elritercept treatment as a monotherapy or in combination with ruxolitinib can continue to receive elritercept in this long-term extension phase until elritercept becomes commercially available or until elritercept is no longer being developed for the treatment of MF.

Group II: Experimental: Arm 2C: Elritercept (Brazil Only) Experimental Treatment 1 Intervention

Participants from Brazil with anemia who have received no prior treatment with JAK inhibitor(s) and have no access to JAK inhibitor therapy will be administered elritercept, 3.75 mg/kg, SC, every 4 weeks for 13 cycles for a total Treatment Period of 52 weeks. Each cycle is 28 days.

Group III: Arm 2B: Elritercept + Ruxolitinib Experimental Treatment 2 Interventions

Participants with anemia who have been receiving ruxolitinib for ≥8 weeks prior to C1D1 and are on a stable dose for ≥4 weeks prior to C1D1 will be administered elritercept, 3.75 mg/kg, SC, every 4 weeks for 13 cycles in combination with ruxolitinib therapy for a total Treatment Period of 52 weeks. Each cycle is 28 days.

Group IV: Arm 2A: Elritercept Experimental Treatment 1 Intervention

Participants with with anemia who have discontinued JAK inhibitor(s) or are intolerant or ineligible for JAK inhibitor(s) will be administered elritercept, 3.75 mg/kg, SC, every 4 weeks for 13 cycles for a total Treatment Period of 52 weeks. Each cycle is 28 days.

Group V: Arm 1B: Elritercept + Ruxolitinib Experimental Treatment 2 Interventions

Participants with anemia who have been receiving ruxolitinib for ≥8 weeks prior to Cycle 1 Day 1 (C1D1) and are on a stable dose for ≥4 weeks prior to C1D1 will be administered escalating doses of elritercept, starting at 0.75 mg/kg and followed by 1.5 mg/kg and 4.5 mg/kg, SC, every 4 weeks for 13 cycles in combination with ruxolitinib therapy for a total Treatment Period of 52 weeks. Each cycle is 28 days.

Group VI: Arm 1A: Elritercept Experimental Treatment 1 Intervention

Participants with anemia who have discontinued Janus Kinase (JAK) inhibitor(s) or are intolerant or ineligible for JAK inhibitor(s) will be administered escalating doses of elritercept, starting at 0.75 milligrams per kilograms (mg/kg) followed by 1.5 mg/kg and 4.5 mg/kg subcutaneously (SC), every 4 weeks for 13 cycles for a total Treatment Period of 52 weeks. Each cycle is 28 days.

Who Is Running the Clinical Trial?

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

Lead Sponsor

Trials

2

Recruited

260+

Keros Therapeutics, Inc.

Lead Sponsor

Trials

5

Recruited

600+

IQVIA Biotech

Industry Sponsor

Trials

22

Recruited

5,900+

Published Research Related to This Trial

Ruxolitinib, the only approved JAK inhibitor for myelofibrosis (MF), has been shown to be effective in managing the disease, significantly changing treatment approaches since its introduction.

While JAK inhibitors can cause side effects like anemia, thrombocytopenia, and increased infection risk, these effects are generally predictable and manageable with careful monitoring and dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing side effects of JAK inhibitors for myelofibrosis in clinical practice. Saeed, I., McLornan, D., Harrison, CN.[2021]

Ruxolitinib is an effective oral treatment for intermediate- or high-risk myelofibrosis, targeting JAK1 and JAK2 to reduce spleen size and improve symptoms, as demonstrated in Phase III trials with significant improvements in quality of life and overall survival.

The treatment has a manageable safety profile, with common side effects including anemia and thrombocytopenia, and requires dosage adjustments based on platelet counts, allowing for personalized patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib for the treatment of primary myelofibrosis. Swaim, SJ.[2021]

In a double-blind trial involving 309 patients with intermediate-2 or high-risk myelofibrosis, ruxolitinib significantly reduced spleen volume by 35% or more in 41.9% of patients compared to only 0.7% in the placebo group, demonstrating its efficacy (P<0.001).

Ruxolitinib also improved overall survival, with a hazard ratio of 0.50 for death compared to placebo, while common side effects included anemia and thrombocytopenia, which were manageable and rarely led to discontinuation of the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. Verstovsek, S., Mesa, RA., Gotlib, J., et al.[2022]

In a study of 219 patients with myelofibrosis, ruxolitinib demonstrated a significant efficacy advantage over the best available therapy, with 28% of patients achieving at least a 35% reduction in spleen volume at 48 weeks, compared to 0% in the control group.

Ruxolitinib not only reduced spleen size but also improved overall quality of life and disease symptoms, with manageable side effects, primarily hematologic issues like thrombocytopenia and anemia, indicating it is a safe and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. Harrison, C., Kiladjian, JJ., Al-Ali, HK., et al.[2022]

JAK inhibitors like ruxolitinib and fedratinib have been approved for treating intermediate-risk and high-risk myelofibrosis, showing improvements in spleen size and quality of life, but they also have high rates of treatment discontinuation due to side effects or disease progression.

There is a significant need for alternative treatments, as outcomes after stopping JAK inhibitors are poor, with survival lasting only 11 to 16 months; thus, various non-JAK inhibitors are being tested in clinical trials to potentially improve treatment options for myelofibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical dilemma of JAK inhibitor failure in myelofibrosis: Predictive characteristics and outcomes. Mascarenhas, JO., Verstovsek, S.[2022]

Ruxolitinib is a dual inhibitor of JAK1 and JAK2, which are crucial in the development of myelofibrosis (MF), and it has been FDA-approved since November 2011 for treating intermediate or high-risk MF.

The review discusses Ruxolitinib's current role in managing MF and explores its potential future applications in treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Janus activated kinase inhibition in myelofibrosis. Malhotra, H.[2021]

In a phase I/II study involving 27 patients with relapsed or refractory acute leukemias, ruxolitinib was found to be reasonably well tolerated, with the most common severe side effect being infections, particularly pneumonia.

One patient achieved a complete response with incomplete recovery of peripheral blood (CRp) at the highest dose of 200 mg b.i.d., indicating potential efficacy in this heavily pretreated population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I/II study of the Janus kinase (JAK)1 and 2 inhibitor ruxolitinib in patients with relapsed or refractory acute myeloid leukemia. Pemmaraju, N., Kantarjian, H., Kadia, T., et al.[2021]

Citations

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Keros Therapeutics Presents Clinical Data from its Elritercept ...

NT patients achieved meaningful improvements in FACIT-Fatigue scores, with improvements seen early, generally within the first two treatment ...

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A 68-year-old male with primary myelofibrosis received ruxolitinib 10 mg twice daily for 7 months. His spleen size and symptoms are controlled, ...

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ashpublications.org/blood/article/144/Supplement%201/997/530418/Hematological-Improvement-and-Other-Clinical

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Data also support potential for elritercept to reduce spleen size and improve TSS as monotherapy and in combination with ruxolitinib. Updated ...

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ELRITERCEPT (KER-050) DEMONSTRATED POTENTIAL TO ...

ELRITERCEPT (KER-050) DEMONSTRATED POTENTIAL TO TREAT MYELOFIBROSIS AND MITIGATE RUXOLITINIB-ASSOCIATED CYTOPENIAS IN THE PHASE 2 RESTORE TRIAL.

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clinicaltrials.gov/study/NCT05037760

NCT05037760 | Study to Evaluate KER-050 as a ...

This is a Phase 2, multicenter, open-label study to evaluate the safety and efficacy of KER-050 as monotherapy or in combination with ruxolitinib in ...

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... Ruxolitinib in Participants with Myelofibrosis from ... Baseline and safety data are for participants who received ≥1 dose of elritercept.

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KER-050 (elritercept) achieved durable transfusion independence in lower-risk MDS, including in patients with high transfusion burden

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healthtree.org

healthtree.org/myelofibrosis/community/articles/ash-24-elritercept-for-myelofibrosis

The Benefits of Elritercept for Myelofibrosis?

Elritercept may help address the anemia associated with myelofibrosis, whether caused by the disease itself or as a side effect of JAK inhibitors.