Evaluate Ofirnoflast in Adults With Very Low- to Intermediate-risk Myelodysplastic Syndromes Requiring Transfusions
2026년 7월 29일 업데이트: 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.
연구 개요
상세 설명
- 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.
연구 유형
중재적
등록 (추정된)
50
단계
- 2 단계
연락처 및 위치
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연구 연락처
- 이름: Associate Medical Director
- 전화번호: 385-355-4315
- 이메일: monitor@haliatx.com
참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
아니
설명
Inclusion Criteria:
- At least 18 years of age at the time of signing informed consent.
- Capable of giving signed informed consent
- Documented diagnosis of very low-, low-, or intermediate-risk MDS
- Documented diagnosis of anemia
- Relapsed or refractory disease after 1 to 3 prior lines of therapy for lower-risk MDS
- Willing to provide a bone marrow aspirate at Screening.
- Life expectancy of more than 6 months at screening.
- Participants of childbearing potential must have a negative pregnancy test at screening (serum) and Day 1 (urine).
- 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:
- Anemia due to other causes (e.g., iron deficiency).
- Known clinically significant anemia due to iron, vitamin B12, or folate deficiency; autoimmune or hereditary hemolytic anemia; or gastrointestinal bleeding.
- History of hemoglobinopathies, intrinsic RBC membrane/enzyme defects, or hemolytic anemia.
- 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.
- Diagnosis of MPN, CMML, or overlap MDS/MPN per WHO classification.
- Any condition or concomitant treatment that may impair absorption of orally administered study intervention.
- Uncontrolled infection or severe organ dysfunction.
- 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).
- Prior treatment with disease-modifying agents (e.g., hypomethylating agents) or immunosuppressive therapy, except prior lenalidomide (permitted).
- Treatment with cytotoxic chemotherapy or experimental agents within 4 weeks prior to first dose.
- History of stem cell, bone marrow, or solid organ transplant.
- Known hypersensitivity to ofirnoflast or its excipients.
- Severe renal or hepatic impairment
- Inability to swallow tablets.
- Participation in another interventional clinical study within 90 days prior to first dose.
- QTcF >480 ms.
- Prior treatment with ofirnoflast.
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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실험적: 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).
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once daily.
다른 이름들:
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실험적: 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).
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once daily.
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Assess safety of ofirnoflast
기간: Weeks 1-24
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The safety and tolerability of ofirnoflast will be evaluated based on the incidence of treatment-emergent adverse events (TEAEs)
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Weeks 1-24
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Assess safety of ofirnoflast
기간: Weeks 1-24
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The safety and tolerability of ofirnoflast will be evaluated based on the incidence dose modifications
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Weeks 1-24
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Assess safety of ofirnoflast
기간: Weeks 1-24
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The safety and tolerability of ofirnoflast will be evaluated based on the pharmacokinetic exposure data
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Weeks 1-24
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Assess the hematologic response to ofirnoflast
기간: Weeks 1-24
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The hematologic response to ofirnoflast will be evaluated by the duration of time the participants do not require red blood cell transfusions
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Weeks 1-24
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Assess the extended hematologic response to ofirnoflast
기간: Weeks 1-24
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The hematologic response to ofirnoflast will be evaluated by the duration of time the participants do not require red blood cell transfusions
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Weeks 1-24
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Assess the hematologic improvement on orfirnoflast
기간: Weeks 1-24
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The hematologic improvement will be evaluated by assessment of platelets
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Weeks 1-24
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Assess the hematologic improvement on orfirnoflast
기간: Weeks 1-24
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The hematologic improvement will be evaluated by assessment of hemoglobin
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Weeks 1-24
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Assess the hematologic improvement on orfirnoflast
기간: Weeks 1-24
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The hematologic improvement will be evaluated by assessment of neutrophils
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Weeks 1-24
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협력자
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (추정된)
2026년 10월 1일
기본 완료 (추정된)
2028년 10월 1일
연구 완료 (추정된)
2028년 12월 1일
연구 등록 날짜
최초 제출
2026년 7월 27일
QC 기준을 충족하는 최초 제출
2026년 7월 29일
처음 게시됨 (실제)
2026년 7월 31일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2026년 7월 31일
QC 기준을 충족하는 마지막 업데이트 제출
2026년 7월 29일
마지막으로 확인됨
2026년 7월 1일
추가 정보
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