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Étude de l'efficacité et de l'innocuité d'eltrombopag chez les patients atteints de SMD à faible risque présentant une dépendance aux transfusions plaquettaires

16 octobre 2026 mis à jour par: Novartis Pharmaceuticals

Une étude clinique de phase II randomisée, en double aveugle, contrôlée par placebo, au Japon, comparant la monothérapie par eltrombopag à un placebo chez des patients adultes présentant un syndrome myélodysplasique (SMD) à faible risque présentant une dépendance aux transfusions plaquettaires

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).

Aperçu de l'étude

Statut

Actif, ne recrute pas

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Réel)

36

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Japon
      • Aomori, Japon, 0308553
        • Novartis Investigative Site
      • Chiba, Japon, 2600852
        • Novartis Investigative Site
      • Fukushima, Japon, 9601295
        • Novartis Investigative Site
      • Gifu, Japon, 5008513
        • Novartis Investigative Site
      • Kumamoto, Japon, 8600008
        • Novartis Investigative Site
      • Osaka, Japon, 5340021
        • Novartis Investigative Site
      • Yamagata, Japon, 9909585
        • Novartis Investigative Site
    • Chiba
      • Narita, Chiba, Japon, 2868523
        • Novartis Investigative Site
    • Fukuoka
      • Kurume, Fukuoka, Japon, 8308543
        • Novartis Investigative Site
    • Hiroshima
      • Ohtake, Hiroshima, Japon, 7390696
        • Novartis Investigative Site
    • Hyōgo
      • Nishinomiya, Hyōgo, Japon, 6638501
        • Novartis Investigative Site
    • Ishikawa-ken
      • Kanazawa, Ishikawa-ken, Japon, 9208530
        • Novartis Investigative Site
    • Kanagawa
      • Isehara, Kanagawa, Japon, 2591193
        • Novartis Investigative Site
      • Yokohama, Kanagawa, Japon, 2210855
        • Novartis Investigative Site
    • Miyagi
      • Sendai, Miyagi, Japon, 9808574
        • Novartis Investigative Site
    • Nagasaki
      • Nagasaki, Nagasaki, Japon, 8528501
        • Novartis Investigative Site
    • Osaka
      • Sakai, Osaka, Japon, 5900197
        • Novartis Investigative Site
    • Tokyo
      • Bunkyo-ku, Tokyo, Japon, 1138603
        • Novartis Investigative Site
      • tabashi City, Tokyo, Japon, 1738606
        • Novartis Investigative Site
    • Yamaguchi
      • Shimonoseki, Yamaguchi, Japon, 7500061
        • Novartis Investigative Site

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

20 ans à 100 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Eltrombopag Arm

Participants randomized to a 1: 1 ratio will take eltrombopag.
Médicament: Eltrombopag

Eltrombopag comes in 12.5 mg & 25 mg tablets and is taken orally once per day (QD)

Autres noms:
  • ETB115
Comparateur placebo: Placebo Arm

Participants randomized to a 1: 1 ratio will take Placebo.
Médicament: Placebo

Placebo comes in 12.5 mg & 25 mg tablets and is taken orally once per day (QD)

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Percentage of participants who achieve platelet transfusion independence at Week 24
Délai: Week 24

Platelet transfusion independence is defined as the absence of platelet transfusion for at least 8 weeks. Platelet count should be higher than the baseline count.
Week 24

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Time to platelet transfusion independence
Délai: Year 1, Year 2

This is defined as time from the date of randomization to the first day of a platelet transfusion-free period lasting at least 8 weeks.
Year 1, Year 2
Duration of platelet transfusion independence
Délai: Year 1, Year 2

This is defined for participants who have achieved platelet transfusion independence only and will be calculated from the first date of platelet transfusion-free resulting in achievement of transfusion independence to the date before becoming platelet transfusion dependent.
Year 1, Year 2
Percentage of participants with platelet transfusion independence
Délai: Year 1, Year 2

Platelet transfusion independence is defined as the absence of platelet transfusion for at least 8 weeks. Platelet count should be higher than the baseline count.
Year 1, Year 2
Percentage of participants with platelet transfusion frequency reduction at Week 24
Délai: Week 24

This is defined as a reduction by at least 50 percent during the 4 prior weeks as compared to the 4 weeks prior to randomization.
Week 24
Percentage of participants with platelet response (Hematologic improvement (HI) - platelet))
Délai: Week 24, Year 1, Year 2

Platelet response is defined as HI-platelet per International Working Group criteria.
Week 24, Year 1, Year 2
Time to platelet response
Délai: Week 24, Year 1, Year 2

This is defined as time from the date of randomization to the first date of achieving the platelet response criteria per modified IWG criteria.
Week 24, Year 1, Year 2
Duration of platelet response
Délai: Week 24, Year 1, Year 2

This is defined for participants who have achieved platelet response and will be calculated from the first date of achieving the platelet response criteria to the date before loss of platelet response per modified IWG criteria.
Week 24, Year 1, Year 2
Percentage of hematologic improvement-erythroid and -neutrophil
Délai: Week 24, Year 1, Year 2

per modified IWG criteria at 24 weeks, Year 1 and 2
Week 24, Year 1, Year 2
Percentage of participants with disease progression excluding relapse after HI
Délai: Week 24, Year 1, Year 2

This is with regards to blast counts for both investigator assessment and central review per modified IWG criteria.
Week 24, Year 1, Year 2
Percentage of participants with relapse after HI and transfusion independence
Délai: Week 24, Year 1, Year 2

The percentage of participants with relapse after HI and transfusion independence at Week 24, Year 1 and 2.
Week 24, Year 1, Year 2
Percentage of participants with progression to Acute myeloid leukemia (AML)
Délai: Week 24, Year 1, Year 2

This is defined as ≥ 20% blasts at Week 24, Year 1 and 2 for both investigator assessment and central review per WHO classification revised 4th edition.
Week 24, Year 1, Year 2
Leukemia free survival (LFS)
Délai: Week 24, Year 1, Year 2

This is defined as time from the date of randomization to progression to AML per WHO classification revised 4th edition of ≥ 20 percent blasts or death due to any cause for both investigator assessment and central review.
Week 24, Year 1, Year 2
Clinically significant bleeding events
Délai: Week 24, Year 1, Year 2

This is defined as ≥ grade 2 events as per WHO bleeding scale.
Week 24, Year 1, Year 2
Overall survival (OS)
Délai: Week 24, Year 1, Year 2

OS is defined as time from randomization to death due to any cause.
Week 24, Year 1, Year 2
Quality of Life measured using QLQ-C30
Délai: Baseline, every 4 weeks until week 52, every 8 weeks after week 52 up to end of treatment or end of post-treatment follow-up, approximately 3.5 years.

The changes from baseline to each visit where measured using QLQ-C30. EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Subject's responses to 28 questions about their physical functioning, disease symptoms, global health status and utilities are scored on a 4-point scale (1=Not at all to 4=Very much), a low score indicates a high / healthy level of functioning. And the responses to 2 questions about health-related QoL are scored on a 7-point scale (1=Very poor to 7=Excellent), a high score indicates a high / healthy level of functioning.

Using linear transformation, raw scores are standardized, so that scores range from 0 to 100.
Baseline, every 4 weeks until week 52, every 8 weeks after week 52 up to end of treatment or end of post-treatment follow-up, approximately 3.5 years.
Pharmacokinetics (PK): Cmax
Délai: Intensive: pre-dose, 1, 2, 4, 6, 8, and 24 hours post-dose. Trough: 15th days after starting the initial dose or each dose modification until reaching the maximum dose.

Full PK profile of eltrombopag over 24 hours at steady state at the initial dose, and at 125 mg and 150 mg when applicable, in subset of participants.
Intensive: pre-dose, 1, 2, 4, 6, 8, and 24 hours post-dose. Trough: 15th days after starting the initial dose or each dose modification until reaching the maximum dose.
PK: Tmax
Délai: Intensive: pre-dose, 1, 2, 4, 6, 8, and 24 hours post-dose. Trough: 15th days after starting the initial dose or each dose modification until reaching the maximum dose.

Full PK profile of eltrombopag over 24 hours at steady state at the initial dose, and at 125 mg and 150 mg when applicable, in subset of participants.
Intensive: pre-dose, 1, 2, 4, 6, 8, and 24 hours post-dose. Trough: 15th days after starting the initial dose or each dose modification until reaching the maximum dose.
PK: AUC
Délai: Intensive: pre-dose, 1, 2, 4, 6, 8, and 24 hours post-dose. Trough: 15th days after starting the initial dose or each dose modification until reaching the maximum dose.

Full PK profile of eltrombopag over 24 hours at steady state at the initial dose, and at 125 mg and 150 mg when applicable, in subset of participants.
Intensive: pre-dose, 1, 2, 4, 6, 8, and 24 hours post-dose. Trough: 15th days after starting the initial dose or each dose modification until reaching the maximum dose.
Trough concentrations of eltrombopag at steady state
Délai: Intensive: pre-dose, 1, 2, 4, 6, 8, and 24 hours post-dose. Trough: 15th days after starting the initial dose or each dose modification until reaching the maximum dose.

at each dose level in all the participants
Intensive: pre-dose, 1, 2, 4, 6, 8, and 24 hours post-dose. Trough: 15th days after starting the initial dose or each dose modification until reaching the maximum dose.

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Novartis Pharmaceuticals

Les enquêteurs

  • Directeur d'études: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

25 mai 2021

Achèvement primaire (Réel)

26 avril 2025

Achèvement de l'étude (Estimé)

2 décembre 2026

Dates d'inscription aux études

Première soumission

4 mars 2021

Première soumission répondant aux critères de contrôle qualité

11 mars 2021

Première publication (Réel)

15 mars 2021

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

20 octobre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

16 octobre 2026

Dernière vérification

1 octobre 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • CETB115L11201

Plan pour les données individuelles des participants (IPD)

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Description du régime IPD

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

Informations sur les médicaments et les dispositifs, documents d'étude

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Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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