A Study to Evaluate Ofirnoflast in Adults With Very Low- to Intermediate-risk Myelodysplastic Syndromes Requiring Red Blood Cell Transfusions

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

The primary objective of this study is to two part. First, dose selection for dose optimization based on safety of ofirnoflast. Second, to evaluate the efficacy of ofirnoflast administered in the study population.

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

Study Overview

• Status: Not yet recruiting
• Conditions: Myelodysplastic Syndromes; Anemia
• Intervention / Treatment: Drug: Ofirnoflast

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Associate Medical Director; Phone Number: 385-355-4315; Email: monitor@haliatx.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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
• Documented low serum erythropoietin level
• 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.
• Eastern Cooperative Group Performance Status (ECOG PS) of 0, 1, or 2
• 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).
• Low platelet count
• Low neutrophil count
• 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.
• Medications or food products that are strong inhibitors, substrates, and inducers of CYP3A4/5, CYP2C9, P-glycoprotein (P-gp) and/or Breast Cancer Resistance Protein (BCRP) may cause drug-drug interactions and should be avoided.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Low dose ofirnoflast; Participants receive low dose ofirnoflast, up to 6 participants total. Treatment continues through the 24-Week Initial Treatment Period and, for participants demonstrating clinical benefit, the Extension Period (up to an additional 24 weeks).	Drug: Ofirnoflast; tablet; Other Names: HT-6184
Experimental: Part 1: Medium-low dose ofirnoflast; Participants receive medium-low dose ofirnoflast, up to 6 participants total. Treatment continues through the 24-Week Initial Treatment Period and, for participants demonstrating clinical benefit, the Extension Period (up to an additional 24 weeks).	Drug: Ofirnoflast; tablet; Other Names: HT-6184
Experimental: Part 1: Medium-high dose ofirnoflast; Participants receive medium-high dose ofirnoflast, up to 6 participants total. Treatment continues through the 24-Week Initial Treatment Period and, for participants demonstrating clinical benefit, the Extension Period (up to an additional 24 weeks).	Drug: Ofirnoflast; tablet; Other Names: HT-6184
Experimental: Part 1: High dose ofirnoflast Optional; Participants receive high dose ofirnoflast, up to 6 participants total. Treatment continues through the 24-Week Initial Treatment Period and, for participants demonstrating clinical benefit, the Extension Period (up to an additional 24 weeks).	Drug: Ofirnoflast; tablet; Other Names: HT-6184
Experimental: Part 2: First Dose ofirnoflast Selected; Twenty participants receive the first selected dose of ofirnoflast, dose to be determined during Part 1 of study. Treatment continues through the 24-Week Initial Treatment Period and, for participants demonstrating clinical benefit, the Extension Period (up to an additional 24 weeks).	Drug: Ofirnoflast; tablet; Other Names: HT-6184
Experimental: Part 2: Second Dose ofirnoflast Selected; Twenty participants receive the second dose of ofirnoflast selected, dose to be determined during Part 1 of study. Treatment continues through the 24-Week Initial Treatment Period and, for participants demonstrating clinical benefit, the Extension Period (up to an additional 24 weeks).	Drug: Ofirnoflast; tablet; Other Names: HT-6184

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose selection for dose optimization	Incidence of dose-limiting toxicities during the 28-day DLT observation window at each dose level to determine the dose levels acceptable for advancement to Part 2.	Days 1-28 of each Part 1 Cohort
Evaluate the efficacy of ofirnoflast in to low- to intermediate-risk MDS who are transfusion dependent	The efficacy will be evaluated by proportion of participants achieving red blood cell transfusion independence for at least 16 consecutive weeks	Weeks 1-24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess safety and tolerability of ofirnoflast across dose levels evaluated	The safety and tolerability of ofirnoflast will be evaluated based on the incidence and severity of TEAEs	Weeks 1-24
Evaluate the overall hematologic response to ofirnoflast	The hematologic response to ofirnoflast will be evaluated by proportion of participants achieving overall response	Weeks 1-24
Evaluate the duration of response in participants achieving transfusion independence with ofirnoflast	The duration of hematologic response to ofirnoflast will be evaluated by the duration of transfusion independence greater than or equal to 16 consecutive weeks	Weeks 1-24
Evaluate the hematologic improvement in participants treated with ofirnoflast	The hematologic improvement will be evaluated by assessment of red blood cells	Weeks 1-24
Evaluate the hematologic improvement in participants treated with ofirnoflast	The hematologic improvement will be evaluated by assessment of platelets	Weeks 1-24
Evaluate the hematologic improvement in participants treated with ofirnoflast	The hematologic improvement will be evaluated by assessment of neutrophils	Weeks 1-24

Collaborators and Investigators

• Sponsor: Halia Therapeutics, Inc.
• Collaborators: Parexel

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: July 27, 2026
• First Submitted That Met QC Criteria: July 29, 2026
• First Posted (Actual): July 31, 2026

Study Record Updates

• Last Update Posted (Actual): October 2, 2026
• Last Update Submitted That Met QC Criteria: September 29, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Ofirnoflast, HT-6184, Myelodysplastic syndromes, MDS
• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Anemia
• Other Study ID Numbers: HT-6184-MDS-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No