Eltrombopag for Aplastic Anemia

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Must not be taking: ATG, Campath, Cytokines, others

Disqualifiers: Fanconi anemia, HIV, Cancer, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 16-20 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the drug eltrombopag can safely and effectively aid individuals with moderate aplastic anemia, a blood disease often requiring frequent transfusions. Eltrombopag, an oral medication, works to increase blood cell production, potentially reducing transfusion needs. The trial seeks participants with moderate aplastic anemia or bone marrow failure with low blood cell counts, which impacts daily life through frequent transfusions or low energy. Participants will take eltrombopag daily and attend regular check-ins to monitor progress. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are currently being treated with certain drugs like horse or rabbit ATG, Campath, cytokines such as G-CSF or Erythropoietin, or have received chemotherapy or radiation therapy within the last 6 months, you may not be eligible to participate.

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

Research shows that eltrombopag is generally well-tolerated by patients with blood disorders like severe aplastic anemia. Studies have found that when used alone, eltrombopag can lead to positive results, with 40-50% of patients responding well after not improving with other treatments. This drug can help increase blood cell counts in some patients.

Regarding safety, eltrombopag has been used safely with other treatments, showing significant improvement in patients' conditions. While all medications can have side effects, eltrombopag's history in treating similar conditions offers some reassurance about its safety. Patients in past studies continued treatment as long as they did not experience serious side effects.

Patients should watch for any changes in their condition and talk to their healthcare provider if they notice anything unusual while on the treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Eltrombopag is unique because it stimulates the production of platelets by acting on a different pathway compared to standard treatments for aplastic anemia, which often include immunosuppressive therapies and bone marrow transplants. Unlike these conventional options, eltrombopag directly targets the thrombopoietin receptor, promoting platelet production without suppressing the immune system. This new mechanism of action offers a promising alternative for patients who do not respond well to existing treatments, potentially improving outcomes and reducing the reliance on more invasive procedures. Researchers are excited about eltrombopag because it could provide a more targeted approach to managing aplastic anemia, offering hope for better patient experiences and results.

What evidence suggests that eltrombopag might be an effective treatment for moderate aplastic anemia?

Research has shown that eltrombopag, the treatment under study in this trial, holds promise for treating blood disorders such as severe aplastic anemia. In previous studies, many patients experienced significant improvements in their blood cell counts. For instance, one study found that 41% of patients taking eltrombopag had an increase in their platelet counts. Another study showed that about 55% of patients responded positively after 26 weeks. This drug mimics thrombopoietin, a protein that helps the bone marrow produce blood cells. These findings suggest eltrombopag could be effective for patients with moderate aplastic anemia who have low blood cell counts. ^{1 2 3 6 7}

Who Is on the Research Team?

Cynthia E Dunbar, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Are You a Good Fit for This Trial?

This trial is for people over 2 years old with moderate aplastic anemia or certain bone marrow failure disorders, who have low blood cell counts and weigh more than 12 kg. They shouldn't have severe aplastic anemia, uncontrolled infections, HIV, significant liver/kidney disease, known sensitivity to eltrombopag, be pregnant/nursing without contraception use if applicable, or unable to consent.

Inclusion Criteria

I am at least 2 years old.

I have been diagnosed with moderate aplastic anemia or a similar bone marrow failure.

Weight greater than 12 kg

Exclusion Criteria

My bilirubin level is higher than 2.0 mg/dL.

My recent tests show active blood cancer or abnormal bone marrow.

Counts that meet criteria for severe aplastic anemia

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive eltrombopag by mouth once a day, with weekly blood tests to monitor effectiveness and adjust dosage

16-20 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a follow-up visit 6 months after the last dose

6 months

1 visit (in-person)

Extended Access

Participants with a clinical response may continue to receive eltrombopag beyond 20 weeks if they meet response criteria

Indefinite until study closure

What Are the Treatments Tested in This Trial?

Interventions

• Eltrombopag

Trial Overview The trial tests the safety and effectiveness of a drug called Eltrombopag in patients with moderate aplastic anemia. Participants will take this medication orally once daily and undergo regular blood tests to adjust dosage based on response and side effects.

How Is the Trial Designed?

Group I: Eltrombopag Experimental Treatment 1 Intervention

Eltrombopag will be administered for 16 to 20 weeks at a starting dose of 50mg/day (East Asian ancestry 25mg/day). The dose will decreased and increased (maximum dose 300mg/day) based on safety and response.

Eltrombopag is already approved in United States, European Union, Canada, Japan, China for the following indications:

Approved in United States as Promacta for:

• Severe aplastic anemia
• Chronic immune thrombocytopenia
• Thrombocytopenia in patients with chronic hepatitis C

Approved in European Union as Revolade for:

• Severe aplastic anemia
• Chronic immune thrombocytopenia

Approved in Canada as Promacta for:

• Severe aplastic anemia
• Chronic immune thrombocytopenia

Approved in Japan as Revolade for:

• Severe aplastic anemia
• Chronic immune thrombocytopenia

Approved in China as Promacta for:

• Severe aplastic anemia
• Chronic immune thrombocytopenia

Who Is Running the Clinical Trial?

National Heart, Lung, and Blood Institute (NHLBI)

Lead Sponsor

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

Eltrombopag is an effective treatment for increasing platelet counts in adults with chronic hepatitis C virus (HCV) infection, enabling 95% of patients to start peginterferon-based antiviral therapy who otherwise would not qualify due to low platelet levels.

While eltrombopag improved the likelihood of achieving a sustained virological response after treatment compared to placebo, the additional benefit was modest (less than 10%), and it carries risks of serious side effects like hepatic decompensation and thromboembolic events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eltrombopag: a review of its use in the treatment of thrombocytopenia in patients with chronic hepatitis C. Burness, CB.[2022]

The FDA Amendments Act of 2007 introduced Risk Evaluation and Mitigation Strategies (REMS) to enhance drug safety, requiring pharmaceutical companies to create safety plans for drugs with uncertain risk-benefit profiles.

Romiplostim (Nplate®), used to treat thrombocytopenia, exemplifies the use of REMS due to its significant safety concerns, including risks of bone marrow changes, highlighting the importance of these strategies in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk evaluation and mitigation strategies (REMS): educating the prescriber. Nicholson, SC., Peterson, J., Yektashenas, B.[2021]

Eltrombopag is an effective treatment for patients with severe aplastic anemia who do not respond to immunosuppressive therapy, showing a hematological response in at least 40% of patients after 12-16 weeks of treatment.

The drug works by stimulating hematopoietic stem cells and increasing platelet, red blood cell, and neutrophil counts, while being generally well tolerated, though it can cause increased liver transaminases and some cytogenetic abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eltrombopag: a review of its use in patients with severe aplastic anaemia. McCormack, PL.[2018]

Eltrombopag, when used in combination with immunosuppressive therapy, shows a high overall hematologic response rate of 88% in patients with aplastic anemia, indicating its efficacy in this treatment context.

In patients with refractory aplastic anemia treated with eltrombopag alone, the response rate drops to 47%, and there are concerns about karyotype abnormalities, with a 17% rate observed in this group, highlighting potential safety issues associated with the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Eltrombopag for Aplastic Anemia: A Systematic Review and Meta-analysis. Hong, Y., Li, X., Wan, B., et al.[2022]

The study evaluated the effect of adding medicines to the additional monitoring (AM) list on adverse drug reaction (ADR) reporting in the European Economic Area, analyzing 11 active substances over 12 months before and after their addition.

While there was no immediate increase in ADR reporting for most products, two new drugs, boceprevir and denosumab-Xgeva, showed a gradual increase in reports, suggesting that the AM list may have a modest impact on ADR awareness for certain medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does additional monitoring status increase the reporting of adverse drug reactions? An interrupted time series analysis of EudraVigilance data. Segec, A., Slattery, J., Morales, DR., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8718619/

Long-term outcomes in patients with severe aplastic ... The majority of treated patients achieved an overall hematologic response rate (ORR) at 6 months, and most importantly, EPAG addition resulted in a more robust ...

2. ashpublications.org ashpublications.org/bloodadvances/article/9/15/3728/537097/Eltrombopag-in-combination-with-immunosuppressive

Eltrombopag in combination with immunosuppressive therapy ... The overall response rate (ORR; per North American Pediatric Aplastic Anemia Consortium criteria) at 26 weeks was 54.9% in both cohorts combined and 71.4% and ...

3. tandfonline.com tandfonline.com/doi/full/10.1080/16078454.2024.2335419

Safety and efficacy of eltrombopag in patients with aplastic ... Eltrombopag combined with immunotherapy showed significant improvements in 6-month CR (OR: 2.20; 95% CI;1.54–3.12; P < 0.0001) and 6-month OR ( ...

4. thejh.org thejh.org/index.php/jh/article/view/1289/850

Long-Term Outcome of Eltrombopag With First-Line ... In contrast, the efficacy of IST is reportedly to be 50-70%, with a recurrence rate of 30% after treatment [2]. Insufficient responses and high ...

5. onclive.com onclive.com/view/generic-eltrombopag-is-now-available-for-severe-aplastic-anemia-and-immune-thrombocytopenia

Generic Eltrombopag Is Now Available for Severe Aplastic ... The same patient population was evaluated in PETIT2, and those treated with eltrombopag (n = 63) achieved a platelet count response rate of 41% ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7940771/

Current evidence and the emerging role of eltrombopag in ... First studies with eltrombopag as a single agent at 150 mg/day showed an overall response rate of 40–50% in patients with refractory severe AA (rSAA).

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01703169

Efficacy and Safety of Eltrombopag In Patients With Severe ... The investigators hypothesis is that eltrombopag given to patients with moderate to very severe aplastic anemia will result in an increase in platelet counts.