This study is designed to evaluate the efficacy and safety of eltrombopag monotherapy in Japanese adult patients with platelet transfusion-dependent lower-risk Myelodysplastic syndromes (LR-MDS).

This is a randomized, double-blind, placebo-controlled, Japanese local phase II study to evaluate the efficacy and safety of eltrombopag monotherapy in Japanese adult patients with platelet transfusion-dependent lower-risk MDS (IPSS-R very low, low, intermediate risk with bone marrow blast count < 5% and cytogenetic very good, good or intermediate risk). Platelet transfusion dependence at baseline is defined as receiving platelet transfusion regularly with a frequency of 2 or more times within 4 weeks prior to randomization. Platelet transfusion should be performed for a patient with platelet counts < 20 X 10^9/L, or with hemorrhagic symptoms and platelet counts < 30 X 10^9/L.

The primary objective is to demonstrate superiority of eltrombopag versus placebo in terms of the proportion of participants who achieve platelet transfusion independence at Week 24.

Inclusion Criteria:

• Patients diagnosed with MDS according to the WHO classification revised 4th edition by investigator assessment with one of the following prognostic risk categories, based on the International

Prognostic Scoring System (IPSS-R):

• very low (0-1.5)

• low (2-3)

• intermediate risks (3.5-4.5) All following criteria for prognostic variables per IPSS-R should be met.

• Bone marrow blast < 5% (per both investigator's assessment and central review)

• Cytogenetic very good, good or intermediate risk corresponding to IPSS-R

  • Platelet transfusion dependence
  • Refractory, intolerant to, or ineligible for MDS treatments
  • Eastern Cooperative Oncology Group (ECOG) Performance status (PS) 0 or 1

Exclusion Criteria:

• Patients with a history of prior administration of eltrombopag, romiplostim, or other TPO-RA
• Therapy-related MDS per WHO classification revised 4th edition
• MDS/myeloproliferative neoplasms including chronic myelomonocytic leukaemia per the WHO classification revised 4th edition
• MDS with excess blasts (EB) per WHO classification revised 4th edition
• Known history of IPSS-R high or very high risk MDS
• Currently receiving treatments for MDS (e.g., HMA, cyclosporine A (CsA) or lenalidomide). Supportive treatment with erythropoiesis-stimulating agents (ESAs) or erythroid mutation agent in anemic patients or granulocyte-colony stimulating factor (G-CSF) in patients with severe neutropenia and recurrent infections is allowed if at stable dosage for 3 months prior to screening and continued at the same dosing/schedule until the optimal dose of eltrombopag has been established.
• Patients scheduled for hematopoietic stem cell transplantation
• Bone marrow fibrosis that leads to an inability to aspirate adequate bone marrow sample
• Known thrombophilic risk factors (except in cases where potential benefits of participating in the study outweighed potential risks of thromboembolic events (TEE), as determined by the investigator)

Other protocol-defined inclusion/exclusion criteria may apply.

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Participants, investigators, site staffs and site monitors will remain blinded to the identity of the treatment from the time of randomization until database lock for final analysis, and the clinical study team members and anyone involved in the Japan registration activities will be blinded until database lock for the primary analysis. Randomization data are kept strictly confidential until the time of unblinding and will not be accessible by anyone else involved in the study with the following exceptions: DMC members and who will perform data analysis for DMC. Once protocol amendment 5 becomes effective, all individuals, including participants, investigators, site staff, and site monitors, will be unblinded.