KER-050 for Myelofibrosis

Recruiting in Palo Alto (17 mi)

+46 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Keros Therapeutics

Must be taking: Ruxolitinib

Must not be taking: TGF-β inhibitors, IMiDs

Disqualifiers: Active infection, Cardiac conditions, Obesity, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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 participants with Myelofibrosis.

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.

What data supports the effectiveness of the drug KER-050 for myelofibrosis?

Ruxolitinib, a component of the treatment, is a drug that has shown significant activity in treating myelofibrosis by improving symptoms and quality of life, and it is approved by the FDA for this condition. ^{1 2 3 4 5}

What is the safety profile of ruxolitinib for myelofibrosis?

Ruxolitinib, used for treating myelofibrosis, is generally considered safe with a predictable side effect profile, including anemia (low red blood cell count), thrombocytopenia (low platelet count), and infection risk, which can be managed with careful monitoring and dose adjustments. ^{1 2 5 6 7}

Research Team

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• KER-050 (Other)
• Ruxolitinib (Other)

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.

Participant Groups

Group I: Arm 2b Experimental Treatment 1 Intervention

Dose Expansion KER-050 (SC, solution for injection, every 4 weeks) in combination with standard of care ruxolitinib (oral, tablet, twice daily)

Group II: Arm 2a Experimental Treatment 1 Intervention

Dose Expansion KER-050 (SC, solution for injection, every 4 weeks) monotherapy

Group III: Arm 2C (front-line monotherapy, Brazil only) Experimental Treatment 1 Intervention

Dose Expansion KER-050 (SC, solution for injection, every 4 weeks) monotherapy

Group IV: Arm 1b Experimental Treatment 1 Intervention

Dose Escalation KER-050 (SC, solution for injection, every 4 weeks) in combination with standard of care ruxolitinib (oral, tablet, twice daily)

Group V: Arm 1a Experimental Treatment 1 Intervention

Dose Escalation KER-050 (SC, solution for injection, every 4 weeks) monotherapy

Who Is Running the Clinical Trial?

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+

Findings from Research

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]

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]

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]

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]

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]

References

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

A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. [2022]

2. India pubmed.ncbi.nlm.nih.gov

Janus activated kinase inhibition in myelofibrosis. [2021]

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

The clinical dilemma of JAK inhibitor failure in myelofibrosis: Predictive characteristics and outcomes. [2022]

4. United States 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. [2021]

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

JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Ruxolitinib for the treatment of primary myelofibrosis. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Managing side effects of JAK inhibitors for myelofibrosis in clinical practice. [2021]