Evaluate Ofirnoflast in Adults With Very Low- to Intermediate-risk Myelodysplastic Syndromes Requiring Transfusions
2026年7月29日 更新者：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.
調査の概要
詳細な説明
- 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.
研究の種類
介入
入学 (推定)
50
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前：Associate Medical Director
- 電話番号：385-355-4315
- メール：monitor@haliatx.com
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
いいえ
説明
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.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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).
|
once daily.
他の名前：
|
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実験的：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).
|
once daily.
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Assess safety of ofirnoflast
時間枠：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
時間枠：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
時間枠：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
時間枠：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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Assess the extended hematologic response to ofirnoflast
時間枠：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
時間枠：Weeks 1-24
|
The hematologic improvement will be evaluated by assessment of platelets
|
Weeks 1-24
|
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Assess the hematologic improvement on orfirnoflast
時間枠：Weeks 1-24
|
The hematologic improvement will be evaluated by assessment of hemoglobin
|
Weeks 1-24
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Assess the hematologic improvement on orfirnoflast
時間枠：Weeks 1-24
|
The hematologic improvement will be evaluated by assessment of neutrophils
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Weeks 1-24
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
協力者
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (推定)
2026年10月1日
一次修了 (推定)
2028年10月1日
研究の完了 (推定)
2028年12月1日
試験登録日
最初に提出
2026年7月27日
QC基準を満たした最初の提出物
2026年7月29日
最初の投稿 (実際)
2026年7月31日
学習記録の更新
投稿された最後の更新 (実際)
2026年7月31日
QC基準を満たした最後の更新が送信されました
2026年7月29日
最終確認日
2026年7月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- HT-6184-MDS-002
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
はい
米国FDA規制機器製品の研究
いいえ
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