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NCT07529951

Study of ZE74-0282 in Patients With JAK2 V617F- or Calreticulin-Mutated Hematologic Disorders

StatusRecruiting
PhasePhase 1
Primary completion (estimated)

At risk: Primary endpoint(s) modified.

See at-risk trials from Eilean Therapeutics

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Record History

All 2 versions: 2 with changes below. See every version on ClinicalTrials.gov ↗

  1. Recruitment opened Show 8 more changesShow less
    • Primary endpoint(s) modified
    • Eligibility criteria expanded, about 265 words
    • Trial arms changed: 8 → 9
    • Study sites: 0 to 2
    • Start date changed from estimate of May 15, 2026 to Jun 1, 2026
    • Secondary endpoints revised (23)
    • Study description expanded, about 162 words
    • Study title expanded, about 1 word
  2. Study First Submitted
  • Notable: the plan changed

Endpoints

Primary

Incidence of Dose-Limiting Toxicities
Timeframe: Cycle 1, Day 1 through Day 28 (each cycle is 28 days)
Determination of the Recommended Phase 2 Dose (RP2D)
Timeframe: During Part 2 dose expansion, using participant data collected from the first dose through approximately 5 months.

Secondary (23)

Incidence, Severity, and Duration of Treatment-Emergent Adverse Events
Incidence of Clinically Significant Hematology Abnormalities
Incidence of Clinically Significant Coagulation Abnormalities
Incidence of Clinically Significant Urinalysis Abnormalities
Incidence of Clinically Significant ECG Abnormalities
Show 18 moreShow less
Incidence of Grade 3 or Higher Adverse Events
Incidence of Serious Adverse Events
Incidence of Treatment-Related Deaths
Maximum Observed Plasma Concentration (Cmax) of ZE74-0282
Time to Maximum Observed Plasma Concentration (Tmax) of ZE74-0282
Minimum Observed Plasma Concentration (Cmin) of ZE74-0282
Steady-State Plasma Concentration (Css) of ZE74-0282
Area Under the Plasma Concentration-Time Curve (AUC) of ZE74-0282
Dose Proportionality of ZE74-0282 with Repeated Escalation
Overall Response Rate (Partial Response or Complete Response)
Time to First Response and Time to Best Response
Duration of Response (DOR)
Overall Survival (OS)
Maximum Reduction in JAK2 V617F or Calreticulin Variant Allele Frequency (VAF)
Proportion of Participants With Elimination of the JAK2 V617F or Calreticulin Clone
Change in Total Symptom Score (TSS)
Change in Bone Marrow Morphology Including Fibrosis
Number of Patients Proceeding to Allogeneic Stem Cell Transplant

Arms and interventions

Part 1 Dose Level -1Experimental

Optional lower dose level. Participants receive ZE74-0282 75 mg QD or, if the BID schedule is selected, 50 mg BID. Approximately 3 to 6 participants may be enrolled. Dosing is oral in continuous 28-day cycles under protocol fasting conditions.

Part 1 Cohort 1a - 150 mg QDExperimental

Participants receive ZE74-0282 150 mg once daily. This is the protocol starting dose. If healthy-volunteer data support BID dosing, Cohort 1a may enroll concurrently with Cohort 1b. The protocol plans 6 to 12 participants across Cohorts 1a and 1b combined. Dosing is oral in continuous 28-day cycles under protocol fasting conditions.

Part 1 Cohort 1b - 75 mg BIDExperimental

If healthy-volunteer data support BID dosing, participants receive ZE74-0282 75 mg twice daily and may enroll concurrently with Cohort 1a. The protocol plans 6 to 12 participants across Cohorts 1a and 1b combined. Dosing is oral in continuous 28-day cycles under protocol fasting conditions.

Part 1 Dose Level 2Experimental

Participants receive ZE74-0282 300 mg QD or 150 mg BID, depending on the dosing schedule selected from emerging pharmacology and safety data. Approximately 3 to 6 participants may be enrolled. For protocol-specified patients assigned to 150 mg BID, step-up dosing over Days 1 to 6 may be used before reaching 150 mg BID.

Part 1 Dose Level 3Experimental

Participants receive ZE74-0282 450 mg QD or 225 mg BID, depending on the dosing schedule selected from emerging pharmacology and safety data. Approximately 3 to 6 participants may be enrolled. Step-up dosing may be used at the Sponsor's discretion.

Part 1 Dose Level 4Experimental

Participants receive ZE74-0282 600 mg QD or 300 mg BID, depending on the dosing schedule selected from emerging pharmacology and safety data. Approximately 3 to 6 participants may be enrolled. Step-up dosing may be used at the Sponsor's discretion.

Part 1 Dose Level 5 / Additional Dose LevelExperimental

Additional ZE74-0282 dose level(s) may be evaluated as needed using approximately 1.33-fold dose increments. If BID dosing is selected, an alternative Dose Level 5 of 400 mg BID is described in the protocol. Approximately 3 to 6 participants may be enrolled per added dose level. Dose levels may be skipped or intermediate levels may be explored based on emerging data.

Part 2 Expansion Dose 1Experimental

Participants are randomized to one of two ZE74-0282 expansion doses selected from Part 1. The selected dose and schedule (QD or BID) will not exceed the MTD and will be evaluated for cumulative safety and tolerability, PK, PD, and preliminary anti-disease activity. Exact dose and target arm size are to be confirmed before Part 2 begins.

Part 2 Expansion Dose 2Experimental

Participants are randomized to one of two ZE74-0282 expansion doses selected from Part 1. The selected dose and schedule (QD or BID) will not exceed the MTD and will be evaluated for cumulative safety and tolerability, PK, PD, and preliminary anti-disease activity. Exact dose and target arm size are to be confirmed before Part 2 begins.

Drugs: ZE74-0282

Sites

2 sites in 2 countries

Australia 1, Uzbekistan 1