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.
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 2
Kontakty a umístění
Studijní kontakt
- Jméno: Associate Medical Director
- Telefonní číslo: 385-355-4315
- E-mail: monitor@haliatx.com
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: 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). |
tablet
Ostatní jména:
|
|
Experimentální: 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). |
tablet
Ostatní jména:
|
|
Experimentální: 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). |
tablet
Ostatní jména:
|
|
Experimentální: 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). |
tablet
Ostatní jména:
|
|
Experimentální: 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). |
tablet
Ostatní jména:
|
|
Experimentální: 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). |
tablet
Ostatní jména:
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Dose selection for dose optimization
Časové okno: Days 1-28 of each Part 1 Cohort
|
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
Časové okno: Weeks 1-24
|
The efficacy will be evaluated by proportion of participants achieving red blood cell transfusion independence for at least 16 consecutive weeks |
Weeks 1-24
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Assess safety and tolerability of ofirnoflast across dose levels evaluated
Časové okno: Weeks 1-24
|
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
Časové okno: Weeks 1-24
|
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
Časové okno: Weeks 1-24
|
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
Časové okno: Weeks 1-24
|
The hematologic improvement will be evaluated by assessment of red blood cells |
Weeks 1-24
|
|
Evaluate the hematologic improvement in participants treated with ofirnoflast
Časové okno: Weeks 1-24
|
The hematologic improvement will be evaluated by assessment of platelets |
Weeks 1-24
|
|
Evaluate the hematologic improvement in participants treated with ofirnoflast
Časové okno: Weeks 1-24
|
The hematologic improvement will be evaluated by assessment of neutrophils |
Weeks 1-24
|
Spolupracovníci a vyšetřovatelé
Sponzor
Spolupracovníci
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- HT-6184-MDS-002
Informace o lécích a zařízeních, studijní dokumenty
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Studuje produkt zařízení regulovaný americkým úřadem FDA
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