MMB for Myelofibrosis

Recruiting at 210 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sierra Oncology LLC - a GSK company

Must be taking: Momelotinib

Disqualifiers: Hypersensitivity to momelotinib, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

237 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It seems focused on participants already receiving momelotinib, so it's best to discuss your specific situation with the trial coordinators.

What data supports the effectiveness of the drug Momelotinib for treating myelofibrosis?

Momelotinib has been shown to improve anemia, reduce spleen size, and alleviate symptoms in patients with myelofibrosis, especially those who are anemic. Clinical trials have demonstrated that it helps patients become less dependent on blood transfusions and may offer survival benefits. ^{1 2 3 4 5}

Is Momelotinib safe for humans?

Momelotinib has been studied in many patients with myelofibrosis, and common side effects include diarrhea, low platelet counts, and anemia. Serious side effects like infections or nerve problems did not increase over time, and the safety profile was consistent without long-term issues. Dose adjustments may be needed for people with severe liver problems. ^{1 2 5 6 7}

How is the drug Momelotinib unique in treating myelofibrosis?

Momelotinib is unique because it not only targets JAK1 and JAK2 like other treatments but also inhibits ACVR1, which helps address anemia and reduces the need for blood transfusions in myelofibrosis patients. This makes it particularly beneficial for patients with anemia, a common issue with other JAK inhibitors. ^{1 3 5 6 8}

What is the purpose of this trial?

This trial aims to provide ongoing access to momelotinib for patients with certain types of myelofibrosis who are already taking the drug and have not seen their disease get worse. The study will also look at how long these patients live without developing leukemia. Momelotinib has been studied for myelofibrosis and other related conditions.

Research Team

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Eligibility Criteria

This trial is for adults with myelofibrosis who are already participating in specific earlier studies of momelotinib (MMB). They must understand and agree to the study's terms. People allergic to MMB or its ingredients cannot join.

Inclusion Criteria

Currently enrolled in Studies GS-US-352-0101, GS-US-352-1214, GS-US-352-1154, or SRA-MMB-301

Able to comprehend and willing to sign the informed consent form

Exclusion Criteria

Known hypersensitivity to MMB, its metabolites, or formulation excipients

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Extended Access Treatment

Participants continue to receive momelotinib as per their previous study regimen until regulatory approval or cessation of product development

Follow-up

Participants are monitored for overall survival and leukemia-free survival

Long-term

Treatment Details

Interventions

• Momelotinib

Trial Overview The trial provides continued access to MMB for patients from previous trials, assessing long-term safety. It also looks at how well participants live without their disease getting worse or developing into leukemia.

Participant Groups

Group I: Cohort 4: Study SRA-MMB-301 Experimental Treatment 1 Intervention

Participants will continue to receive the same dosage regimen as in the previous MMB study SRA-MMB-301 until MMB receives regulatory approval and is commercially available, or development of the product ceases.

Group II: Cohort 3: Study GS-US-352-1154 Experimental Treatment 1 Intervention

Participants will continue to receive the same dosage regimen as in the previous MMB study GS-US-352-1154 until MMB receives regulatory approval and is commercially available, or development of the product ceases..

Group III: Cohort 2: Study GS-US-352-1214 Experimental Treatment 1 Intervention

Participants will continue to receive the same dosage regimen as in the previous MMB study GS-US-352-1214 until MMB receives regulatory approval and is commercially available, or development of the product ceases.

Group IV: Cohort 1: Study GS-US-352-0101 Experimental Treatment 1 Intervention

Participants will continue to receive the same dosage regimen as in the previous MMB study GS-US-352-0101 until MMB receives regulatory approval and is commercially available, or development of the product ceases.

Momelotinib is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Ojjaara for:

• Intermediate or high-risk myelofibrosis in adults with anemia

Approved in European Union as Ojjaara for:

• Disease-related splenomegaly or symptoms in adults with moderate-to-severe anemia who have primary myelofibrosis, post-polycythaemia vera myelofibrosis or post-essential thrombocythaemia myelofibrosis

Approved in Canada as Ojjaara for:

• Splenomegaly and/or disease-related symptoms in adult patients with intermediate- or high-risk primary myelofibrosis, post–polycythemia vera or essential thrombocythemia myelofibrosis who have moderate-to-severe anemia

Who Is Running the Clinical Trial?

Sierra Oncology LLC - a GSK company

Lead Sponsor

Trials

20

Recruited

2,000+

GlaxoSmithKline

Lead Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Sierra Oncology, Inc.

Lead Sponsor

Trials

20

Recruited

2,000+

Findings from Research

Momelotinib, a novel JAK1 and JAK2 inhibitor that also targets ACVR1, has shown significant improvements in symptoms of myelofibrosis, including splenomegaly and anemia, based on data from 725 patients across three phase 3 studies.

The long-term safety profile of momelotinib is consistent, with the most common side effect being diarrhea, and no increase in serious adverse events over time, indicating it does not lead to long-term toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Momelotinib long-term safety and survival in myelofibrosis: integrated analysis of phase 3 randomized controlled trials. Verstovsek, S., Mesa, R., Gupta, V., et al.[2023]

Momelotinib (MMB) shows comparable efficacy to ruxolitinib in treating myelofibrosis, particularly in improving spleen size and symptoms, while also unexpectedly improving anemia in patients.

A potential drawback of MMB is the risk of treatment-emerged peripheral neuropathy, which may affect its approval; however, optimizing administration could enhance its safety profile and make it a suitable option for patients with anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Momelotinib for the treatment of myelofibrosis. Xu, L., Feng, J., Gao, G., et al.[2019]

Momelotinib has shown significant benefits in treating anemia in myelofibrosis patients by inhibiting specific pathways, leading to decreased hepcidin levels and improved iron and hemoglobin levels, with 41% of patients achieving transfusion independence for at least 12 weeks in a phase 2 study.

In phase 3 trials, momelotinib demonstrated a higher rate of transfusion independence compared to ruxolitinib, particularly in JAK inhibitor-treated patients, suggesting it could be a crucial treatment option for myelofibrosis patients suffering from anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Momelotinib: an emerging treatment for myelofibrosis patients with anemia. Chifotides, HT., Bose, P., Verstovsek, S.[2022]

Momelotinib, an oral inhibitor targeting JAK1/JAK2 and ACVR1, has been approved in the USA for treating intermediate or high-risk myelofibrosis (MF) in adults with anemia, marking a significant advancement in MF treatment.

The approval of momelotinib is particularly important for patients with primary MF or secondary MF (post-polycythemia vera and post-essential thrombocythemia), providing a new therapeutic option for this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Momelotinib: First Approval. Keam, SJ.[2023]

In a phase 1/2 trial involving 100 patients with high/intermediate-risk myelofibrosis, treatment with the JAK1/2 inhibitor momelotinib led to clinical improvement in 57% of patients, particularly in those without ASXL1 mutations and with low circulating blasts.

Despite some patients experiencing significant side effects, such as thrombocytopenia and peripheral neuropathy, the overall survival after discontinuation of momelotinib was similar to that of a comparable group of patients not receiving the treatment, suggesting that while momelotinib may provide some benefits, it does not significantly alter long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Momelotinib therapy for myelofibrosis: a 7-year follow-up. Tefferi, A., Barraco, D., Lasho, TL., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

MOMENTUM: momelotinib vs danazol in patients with myelofibrosis previously treated with JAKi who are symptomatic and anemic. [2021]

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

Momelotinib long-term safety and survival in myelofibrosis: integrated analysis of phase 3 randomized controlled trials. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Momelotinib for the treatment of myelofibrosis. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Momelotinib: an emerging treatment for myelofibrosis patients with anemia. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Momelotinib: First Approval. [2023]

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

Momelotinib therapy for myelofibrosis: a 7-year follow-up. [2020]

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

Pharmacokinetics and Safety of Momelotinib in Subjects With Hepatic or Renal Impairment. [2019]

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

ACVR1/JAK1/JAK2 inhibitor momelotinib reverses transfusion dependency and suppresses hepcidin in myelofibrosis phase 2 trial. [2021]