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Evaluate Ofirnoflast in Adults With Very Low- to Intermediate-risk Myelodysplastic Syndromes Requiring Transfusions

29 de julho de 2026 atualizado por: Halia Therapeutics, Inc.

A Phase 2b, Multicenter, Open-label, Randomized, Dose Optimization Study of Ofirnoflast (HT-6184) for the Treatment of Anemia in Adults With Very Low- to Intermediate-Risk Myelodysplastic Syndromes Requiring Red Blood Cell Transfusions

The primary objective of this study is to evaluate the efficacy and safety of ofirnoflast administered orally once daily in adults with very low- to intermediate-risk myelodysplastic syndromes (MDS) who are transfusion-dependent and have failed one to three prior therapies, in order to identify the optimal dose for continuation into a Phase 3 study.

The secondary objectives of this study are to evaluate the extended hematologic response to ofirnoflast, to assess the safety and tolerability of ofirnoflast during the dose-selection phase, and to evaluate hematologic improvement with ofirnoflast treatment.

Visão geral do estudo

Status

Ainda não está recrutando

Condições

Intervenção / Tratamento

Descrição detalhada

  • Ofirnoflast (HT-6184) is a first-in-class, orally administered small-molecule allosteric inhibitor of the NIMA-related protein kinase 7 (NEK7)-NLRP3 inflammasome, developed to address the inflammatory mechanisms implicated in ineffective hematopoiesis in myelodysplastic syndromes (MDS). Chronic activation of the NLRP3 inflammasome in MDS triggers pyroptosis, driving the ineffective hematopoiesis and cytopenias that define the disease. By selectively targeting NEK7, an essential mediator of NLRP3 assembly, ofirnoflast disrupts this inflammatory cascade without broadly suppressing innate immunity, with the goal of restoring hematopoiesis.
  • Participants with very low- to intermediate-risk MDS who have failed one or more prior lines of therapy face limited treatment options and often develop chronic, symptomatic cytopenias requiring ongoing red blood cell (RBC) transfusions, which are associated with iron overload, reduced quality of life, and increased healthcare utilization. This study is designed to evaluate ofirnoflast in this defined, multiply-relapsed population and to identify the optimal dose to advance into a Phase 3 study.
  • Enrollment will proceed in two sequential phases. Phase A (Safety Lead-in) will open with five participants administered ofirnoflast, observed for a minimum of 4 weeks. Following this observation period, the Safety Review Committee (SRC) will conduct a formal safety review; if no more than 1 of the 5 participants experiences a dose-limiting toxicity (DLT), enrollment will proceed to Phase B. Phase B (Randomized Enrollment) will dose arms concurrently with an additional formal safety review conducted by the SRC after the first 10 participants randomized.
  • For all participants, the study consists of four periods. A Screening Period of up to 28 days prior to first dose will be used to confirm eligibility. A 24-Week Initial Treatment Period begins on Day 1 with administration of the first dose and continues for 24 weeks; all participants receive study intervention for a minimum of 24 weeks to allow complete assessment of hematologic response, with the primary endpoint evaluated during Weeks 1-24 using a landmark assessment at Week 24 to ensure comparability across the population. An Extension Period begins after Week 24 for participants who demonstrate clinical benefit as determined by the investigator; these participants may continue ofirnoflast at their established dose until disease progression.
  • The SRC will conduct a dose-selection analysis after enrollment is complete and the last enrolled participant has completed 8 weeks of dosing, with final analysis following completion of the 24-week Initial Treatment Period. Dose selection will be based on a pre-specified composite assessment incorporating RBC transfusion-independence and hematologic improvement response rates by arm, incidence and severity of treatment-emergent adverse events, dose modifications and discontinuations due to toxicity, and pharmacokinetic exposure parameters.
  • The SRC will monitor participant safety, including safety signal detection, throughout the study, with the frequency of routine safety reviews subject to adjustment based on observed enrollment rate. All participants will receive best supportive care throughout the study.

Tipo de estudo

Intervencional

Inscrição (Estimado)

50

Estágio

  • Fase 2

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

  • Nome: Associate Medical Director
  • Número de telefone: 385-355-4315
  • E-mail: monitor@haliatx.com

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

  • Adulto
  • Adulto mais velho

Aceita Voluntários Saudáveis

Não

Descrição

Inclusion Criteria:

  1. At least 18 years of age at the time of signing informed consent.
  2. Capable of giving signed informed consent
  3. Documented diagnosis of very low-, low-, or intermediate-risk MDS
  4. Documented diagnosis of anemia
  5. Relapsed or refractory disease after 1 to 3 prior lines of therapy for lower-risk MDS
  6. Willing to provide a bone marrow aspirate at Screening.
  7. Life expectancy of more than 6 months at screening.
  8. Participants of childbearing potential must have a negative pregnancy test at screening (serum) and Day 1 (urine).
  9. Participants and partners must use contraception consistent with local regulations and protocol-defined criteria during the intervention period and for at least 30 days after the last dose; periodic abstinence and withdrawal are not acceptable methods.

Exclusion Criteria:

  1. Anemia due to other causes (e.g., iron deficiency).
  2. Known clinically significant anemia due to iron, vitamin B12, or folate deficiency; autoimmune or hereditary hemolytic anemia; or gastrointestinal bleeding.
  3. History of hemoglobinopathies, intrinsic RBC membrane/enzyme defects, or hemolytic anemia.
  4. Prior history of AML, secondary MDS, or other malignancy (except non-melanoma skin cancer or in situ cervical/breast carcinoma) unless disease-free for >1 year.
  5. Diagnosis of MPN, CMML, or overlap MDS/MPN per WHO classification.
  6. Any condition or concomitant treatment that may impair absorption of orally administered study intervention.
  7. Uncontrolled infection or severe organ dysfunction.
  8. Concomitant intercurrent illness or condition that, per investigator judgment, would compromise safe participation (e.g., uncontrolled hypertension, uncontrolled seizure, unstable angina, new-onset/exacerbated cardiac arrhythmia).
  9. Prior treatment with disease-modifying agents (e.g., hypomethylating agents) or immunosuppressive therapy, except prior lenalidomide (permitted).
  10. Treatment with cytotoxic chemotherapy or experimental agents within 4 weeks prior to first dose.
  11. History of stem cell, bone marrow, or solid organ transplant.
  12. Known hypersensitivity to ofirnoflast or its excipients.
  13. Severe renal or hepatic impairment
  14. Inability to swallow tablets.
  15. Participation in another interventional clinical study within 90 days prior to first dose.
  16. QTcF >480 ms.
  17. Prior treatment with ofirnoflast.

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: Arm 1: Ofirnoflast
Participants receive ofirnoflast once daily, including the 5 participants enrolled in the Phase A safety lead-in cohort. Treatment continues through the 24-Week Initial Treatment Period and, for participants demonstrating clinical benefit, the Extension Period (up to an additional 24 weeks).
Medicamento: Ofirnoflast
once daily.
Outros nomes:
  • HT-6184
Experimental: Arm 2: Ofirnoflast
Participants randomized to this arm in Phase B receive ofirnoflast once daily. Treatment continues through the 24-Week Initial Treatment Period and, for participants demonstrating clinical benefit, the Extension Period (up to an additional 24 weeks).
Medicamento: Ofirnoflast
once daily.
Outros nomes:
  • HT-6184

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Assess safety of ofirnoflast
Prazo: Weeks 1-24
The safety and tolerability of ofirnoflast will be evaluated based on the incidence of treatment-emergent adverse events (TEAEs)
Weeks 1-24
Assess safety of ofirnoflast
Prazo: Weeks 1-24
The safety and tolerability of ofirnoflast will be evaluated based on the incidence dose modifications
Weeks 1-24
Assess safety of ofirnoflast
Prazo: Weeks 1-24
The safety and tolerability of ofirnoflast will be evaluated based on the pharmacokinetic exposure data
Weeks 1-24
Assess the hematologic response to ofirnoflast
Prazo: Weeks 1-24
The hematologic response to ofirnoflast will be evaluated by the duration of time the participants do not require red blood cell transfusions
Weeks 1-24

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Assess the extended hematologic response to ofirnoflast
Prazo: Weeks 1-24
The hematologic response to ofirnoflast will be evaluated by the duration of time the participants do not require red blood cell transfusions
Weeks 1-24
Assess the hematologic improvement on orfirnoflast
Prazo: Weeks 1-24
The hematologic improvement will be evaluated by assessment of platelets
Weeks 1-24
Assess the hematologic improvement on orfirnoflast
Prazo: Weeks 1-24
The hematologic improvement will be evaluated by assessment of hemoglobin
Weeks 1-24
Assess the hematologic improvement on orfirnoflast
Prazo: Weeks 1-24
The hematologic improvement will be evaluated by assessment of neutrophils
Weeks 1-24

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Halia Therapeutics, Inc.

Colaboradores

Parexel

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Estimado)

1 de outubro de 2026

Conclusão Primária (Estimado)

1 de outubro de 2028

Conclusão do estudo (Estimado)

1 de dezembro de 2028

Datas de inscrição no estudo

Enviado pela primeira vez

27 de julho de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

29 de julho de 2026

Primeira postagem (Real)

31 de julho de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

31 de julho de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

29 de julho de 2026

Última verificação

1 de julho de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • HT-6184-MDS-002

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Sim

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

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