MMB for Myelofibrosis

Not currently recruiting at 270 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on understanding the long-term safety of momelotinib, a treatment for myelofibrosis, a bone marrow disorder that disrupts blood cell production. Researchers aim to assess the treatment's effectiveness over time and its impact on survival without progression to leukemia. Participants will maintain their current dosage of momelotinib from previous trials. This trial suits those already enrolled in specific momelotinib studies who continue to benefit from the medication without worsening conditions. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that momelotinib is likely to be safe for humans?

Research has shown that momelotinib, a treatment for myelofibrosis, has undergone safety testing in people. In one study, about 35% of patients experienced serious side effects. However, many have used momelotinib safely for five years or more. The FDA has approved it for treating myelofibrosis with anemia, indicating it is considered safe when used as directed. While side effects can occur, current research suggests the benefits outweigh the risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for myelofibrosis?

Researchers are excited about momelotinib for treating myelofibrosis because it targets key pathways involved in the disease differently than existing options. While most current treatments, like ruxolitinib, focus primarily on inhibiting the JAK2 pathway, momelotinib also addresses anemia by inhibiting the ACVR1 pathway, which can improve blood cell production. This dual action could potentially offer better symptom management and improve quality of life for patients. Additionally, momelotinib may help reduce the need for blood transfusions, which is a significant advantage over current therapies.

What evidence suggests that momelotinib might be an effective treatment for myelofibrosis?

Research has shown that momelotinib (MMB) can help people with myelofibrosis. In one study, 27% of patients no longer needed blood transfusions after 24 weeks because their bodies could produce enough blood independently. Another study found that momelotinib significantly reduced spleen size for many patients, easing discomfort and other symptoms. The treatment also improved anemia, a common issue with this condition characterized by a low red blood cell count. Overall, these findings suggest that momelotinib can be a promising option for managing myelofibrosis symptoms. Participants in this trial will continue to receive the same dosage regimen as in previous MMB studies until MMB receives regulatory approval and becomes commercially available, or until development of the product ceases. ^{1 3 4 6 7}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12006532/

Real world outcomes of momelotinib in myelofibrosis patients ... In the MOMENTUM trial [9], 27% of patients achieved transfusion independence at week 24, while our study reported a substantially higher rate of ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40904935/

Efficacy and Safety of Momelotinib in Myelofibrosis Primary outcomes included spleen volume reduction (≥ 35%) and anemia response (transfusion independence). Secondary endpoints included symptom ...

3. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/216873Orig1s000IntegratedR.pdf

216873Orig1s000 INTEGRATED REVIEW - accessdata.fda.gov Momelotinib indicated for the treatment of intermediate- or high-risk myelofibrosis (MF), including primary MF or secondary MF (post- ...

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/216873s000lbl.pdf

OJJAARA (momelotinib) tablets - accessdata.fda.gov Serious adverse reactions occurred in 35% of patients who received OJJAARA during the randomized treatment period of the MOMENTUM trial; the most common serious ...

5. ojjaarahcp.com ojjaarahcp.com/efficacy/jak-inhibitor-experienced/

JAKi Experienced Patients with Anemia | Efficacy | For HCPs MOMENTUM clinical trial results · 25% of patients achieved a TSS reduction of ≥50% at Week 24 with OJJAARA · 30% of patients achieved TI with OJJAARA at Week 24 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10368854/

Momelotinib long-term safety and survival in myelofibrosis In this large, heterogeneous MF data set evaluating a JAK inhibitor, 12% of patients received momelotinib for ≥5 years.

7. ojjaarahcp.com ojjaarahcp.com/

OJJAARA (momelotinib): Myelofibrosis with Anemia Treatment The first & only FDA-approved JAK inhibitor indicated specifically for patients who have myelofibrosis with anemia.