Evaluation of Eltrombopag in the Management of Thrombocytopenia in Patients with Low- and Intermediate-Risk Myelodysplastic Syndromes

The primary objective of this study is to evaluate the effect of **eltrombopag** treatment relative to placebo in patients with thrombocytopenia due to low- and intermediate-risk **myelodysplastic syndromes**. The primary endpoints include assessing the response rate, defined as the proportion of patients achieving a complete response (CR) or response (R) during the treatment period, and evaluating safety and tolerability through the frequency of adverse events (AE) and serious adverse events (SAE). Additionally, the study aims to assess the duration of platelet response and long-term safety and tolerability.

The secondary objectives are to evaluate the effect of treatment relative to placebo on several clinical outcomes:

• Quality of life (QoL) scores
• Number of monthly platelet transfusions
• Duration of transfusion independence
• Time to response, measured from treatment initiation to achievement of CR or PR, using the MDS response criteria
• Incidence and severity of bleeding, assessed with the WHO Bleeding Scale
• Overall survival (OS) at 2 and 5 years
• Leukemia-free survival (LFS) at 2 and 5 years, with events defined as death and progression to acute myeloid leukemia (AML)
• Population pharmacokinetics of eltrombopag

The clinical trial involves participants diagnosed with **myelodysplastic syndromes** (MDS), specifically those classified as low or intermediate-1 risk according to the International Prognostic Scoring System (IPSS). The study population includes both male and female adults aged 18 years and older. Participants are required to have stable disease and meet specific health criteria, such as a platelet count of less than 30 Gi/L and an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-3. The trial includes individuals who are ineligible or have relapsed or are refractory to other treatment options, such as azacitidine or lenalidomide, and are not candidates for intensive chemotherapy or stem cell transplantation. Participants must practice an acceptable method of contraception if of childbearing potential. The trial population was selected based on these criteria, and the sponsor has not provided the total number of participants. Lifestyle considerations such as diet and physical activity are not specified, but the use of erythropoiesis-stimulating agents (ESAs) or granulocyte colony-stimulating factor (G-CSF) is permitted under certain conditions. The trial also includes a vulnerable population, although specific details are not disclosed.

The clinical trial is designed to evaluate the efficacy and safety of **eltrombopag** in treating thrombocytopenia associated with low- and intermediate-risk **myelodysplastic syndromes**. This is a Phase II, randomized, double-blind, placebo-controlled study. The trial is expected to run until October 31, 2026, with participant recruitment having commenced on June 11, 2011. The study involves the administration of **Revolade** (eltrombopag) in the form of 25 mg and 50 mg film-coated tablets, taken orally. The maximum treatment period for participants is 60 days, with a maximum daily dose of 300 mg.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, disease stability, and platelet count. Eligible participants are adults with low or intermediate-1 IPSS risk MDS, who are ineligible or have relapsed or are refractory to other treatment options. The screening process will also ensure that participants have adequate baseline organ function and are practicing acceptable contraception methods if applicable.

Following randomization, participants will attend regular follow-up visits to monitor response rates, safety, and tolerability, including the frequency of adverse events and serious adverse events. The primary endpoints for Phase 1 include the proportion of patients achieving a complete response or response during the six-month treatment period, as well as safety and tolerability parameters. Phase 2 will focus on the duration of platelet response and long-term safety and tolerability.

The end-of-study visit will conclude the participant's involvement, assessing the overall treatment outcomes and any long-term effects. Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with the study protocol, or if the investigator deems it necessary for their safety. The study will also explore secondary endpoints such as changes in quality of life scores, frequency of platelet transfusions, and pharmacokinetic parameters of eltrombopag.

The clinical trial involves the administration of **eltrombopag**, marketed under the name Revolade, in two different dosages: 50 mg and 25 mg film-coated tablets. The active substance, eltrombopag, is a chemical compound with the synonym SB 497115. The pharmaceutical form of the medication is a film-coated tablet, designed for **oral use**. The maximum daily dose for both the 50 mg and 25 mg formulations is 300 mg, with a total treatment period not exceeding 60 days. The medication is manufactured by Novartis Europharm Limited and is authorized for use in the European Union under the marketing authorization numbers EU/1/10/612/006 for the 50 mg tablets and EU/1/10/612/001 for the 25 mg tablets.

In this trial, the primary objective is to evaluate the effect of eltrombopag relative to a placebo on the response rate and safety profile in patients with thrombocytopenia due to low- and intermediate-risk myelodysplastic syndromes. The trial is structured in two phases. Phase 1 focuses on the response rate and safety, while Phase 2 assesses the duration of platelet response and long-term safety. The trial does not include any non-experimental treatments such as standard-of-care therapy or comparator treatments. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the prescribed regimen.

Efficacy in the clinical trial evaluating **Eltrombopag** for the treatment of thrombocytopenia due to low- and intermediate-risk myelodysplastic syndromes will be assessed through several primary and secondary endpoints. In Phase 1, the primary efficacy endpoint is the proportion of patients achieving a complete response (CR) or response (R) during the six-month treatment period. Safety and tolerability will also be evaluated, focusing on non-hematological laboratory Grade 3/Grade 4 toxicities, changes in bone marrow blast counts from baseline, and adverse events. In Phase 2, the primary endpoint is the duration of platelet response.

Secondary endpoints include changes in quality of life (QoL) scores, frequency of platelet transfusions during treatment and follow-up periods, duration of platelet transfusion independence, and the difference in time to response. Additional secondary measures involve the duration of response during treatment and follow-up, incidence and severity of bleeding using the WHO Bleeding Scale, overall survival (OS) and leukemia-free survival (LFS), and the pharmacokinetic parameters of **Eltrombopag**. The relationship between **Eltrombopag** pharmacokinetics and relevant safety and efficacy endpoints will be explored as data permit.