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

34 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: * Moderate aplastic anemia is a blood disease which may require frequent blood and platelet transfusions. Sometimes patients with this disease can be treated with immunosuppressive drugs. Not all patients respond and not all patients are suitable for this treatment. * Thrombopoietin (TPO) is a protein made by the body. The bone marrow needs TPO to produce platelets. TPO may also be able to stimulate bone marrow stem cells to produce red cells and white cells. However, TPO cannot be given by mouth. This has led researchers to develop the drug eltrombopag, which acts in the same way and can be given by mouth. Eltrombopag has been shown to safely increase platelet numbers in healthy volunteers and in patients with other chronic blood diseases, including severe aplastic anemia. Researchers are interested in looking at whether eltrombopag can be given to people with moderate aplastic anemia and significantly low blood cell counts. Objectives: - To evaluate the safety and effectiveness of eltrombopag in people with moderate aplastic anemia or patients with bone marrow failure and unilineage cytopenia who need treatment for significantly low blood cell counts. Eligibility: - People at least 2 years of age who have moderate aplastic anemia or bone marrow failure and unilineage cytopenia,and significantly low blood cell counts. Design: * Patients will be screened with a physical examination, medical history, blood tests, a bone marrow biopsy, and an eye exam. * Patients will receive eltrombopag by mouth once a day. * Patients will have weekly blood tests to monitor the effectiveness of the treatment and adjust the dose in response to possible side effects. * Patients may continue to take eltrombopag if their platelet count or hemoglobin increases, their requirement for platelet or blood transfusion decreases after 16 to 20 weeks of treatment, and there have been no serious side effects. Access to the drug will continue until the study is closed. Patients will be asked to return for a follow-up visit 6 months after the last dose of medication.

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.

What data supports the effectiveness of the drug Eltrombopag for treating aplastic anemia?

Eltrombopag has been shown to increase blood cell counts in patients with severe aplastic anemia who did not respond to other treatments, with 40% of patients experiencing a positive blood cell response. It is also effective in increasing platelet counts in patients with chronic hepatitis C, allowing them to undergo antiviral therapy. ^{1 2 3 4 5}

What safety data exists for Eltrombopag (Promacta, Revolade) in humans?

There is no specific safety data for Eltrombopag (Promacta, Revolade) in the provided research articles. ^{6 7 8 9 10}

How is the drug Eltrombopag unique in treating aplastic anemia?

Eltrombopag is unique because it is an oral drug that stimulates blood cell production by activating thrombopoietin receptors, which helps increase platelet, red blood cell, and neutrophil counts in patients with aplastic anemia, especially those who do not respond to standard immunosuppressive therapy. ^{1 2 3 5 11}

Research Team

Cynthia E Dunbar, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Eligibility Criteria

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.

I have been diagnosed with Fanconi anemia.

Counts that meet criteria for severe aplastic anemia

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

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

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

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

Efficacy and Safety of Eltrombopag for Aplastic Anemia: A Systematic Review and Meta-analysis. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

Hematologic recovery induced by eltrombopag in Japanese patients with aplastic anemia refractory or intolerant to immunosuppressive therapy. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy of eltrombopag with immunosuppressive therapy for children with acquired aplastic anemia. [2023]

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

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

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

Risk evaluation and mitigation strategies (REMS): educating the prescriber. [2021]

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

Low-Dose Elagolix for the Treatment of Heavy Menstrual Bleeding in Patients With Uterine Leiomyomas: A Randomized Controlled Trial. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

[The new pharmacovigilance legislation in practice]. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Does additional monitoring status increase the reporting of adverse drug reactions? An interrupted time series analysis of EudraVigilance data. [2022]

10. Norway pubmed.ncbi.nlm.nih.gov

[Patient reporting of adverse drug reactions in Norway 2010-13]. [2015]

11. Switzerland pubmed.ncbi.nlm.nih.gov

The efficacy and the safety of eltrombopag in pediatric patients with severe aplastic anemia: a systematic review. [2023]