Safety and Tolerability of ZE74-0282 in Healthy Volunteers

NCT07527221 | Recruiting Phase 1

• 1 other identifier: ZE74-0282-0001
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

This first-in-human, randomized, double-blind, placebo-controlled Phase 1 study evaluates the safety, tolerability, and pharmacokinetics of single, split, and multiple oral doses of ZE74-0282 under fasted or fed conditions in healthy adult volunteers.

Conditions

Healthy Volunteers

Keywords

myelofibrosis; polycythaemia vera; essential thrombocytosis; chronic myeloid leukemia

Outcome Measures

Primary Outcomes (11)

• Incidence of AEs/SAEs

  Number of participants with Adverse Events (AEs), serious Adverse Events (SAEs) (including withdrawals due to AEs)

  Baseline to Day 8

• Change from Baseline in body weight

  A measure of change from Baseline in body weight

  Baseline to Day 8

• Change from Baseline in blood pressure

  A measure of change from Baseline in blood pressure

  Baseline to Day 8

• Change from Baseline in electrocardiogram (ECG) QT interval

  A measure of change from Baseline in ECG QT interval

  Baseline to Day 8

• Change from Baseline in haematology parameters

  Change from baseline in Haematocrit, Haemoglobin, Mean corpuscular haemoglobin, Mean corpuscular haemoglobin concentration, Mean corpuscular volume, Mean platelet volume, Packed cell volume, Platelet count, Red blood cell count, Reticulocyte count, White blood cell count.

  Baseline to Day 8

• Change from Baseline in pulse rate

  A measure of change from Baseline in pulse rate

  Baseline to Day 8

• Change from Baseline in respiratory rate

  A measure of change from Baseline in respiratory rate

  Baseline to Day 8

• Change from Baseline in temperature

  A measure of change from Baseline in temperature

  Baseline to Day 8

• Change from Baseline in clinical chemistry parameters

  Change from baseline in Albumin, Alkaline phosphatase, Alanine aminotransferase, Amylase, Anion gap, Aspartate aminotransferase, Bicarbonate, Calcium, Ionised calcium, Chloride, Conjugated (direct) bilirubin, Creatinine, Creatinine kinase.

  Baseline to Day 8

• Change from baseline in coagulation parameters

  Change from baseline in Activated partial thromboplastin time, Fibrinogen, International normalised ratio/ Prothrombin time

  Baseline to Day 8

• Change from Baseline in urinalysis parameters

  Change from baseline in Bilirubin, Blood, Glucose, Ketones, Leukocyte esterase, Nitrite, pH, Protein, Specific gravity, Urobilinogen.

  Baseline to Day 8

Secondary Outcomes (14)

• Maximum observed plasma concentration

  PK samples will be collected from Day 1 to Day 4 and on Day 8

• Time to Cmax

  PK samples will be collected from Day 1 to Day 4 and on Day 8

• Area under the concentration-time curve from 0 to time of last quantifiable concentration

  PK samples will be collected from Day 1 to Day 4 and on Day 8

• Area under the concentration-time curve from 0 to 24 hours

  PK samples will be collected from Day 1 to Day 4 and on Day 8

• Area under the concentration-time curve from 0 to infinity

  PK samples will be collected from Day 1 to Day 4 and on Day 8

Other Outcomes (3)

• Comparison of trough concentrations after 150 mg single-dose and 75 mg BID split-dose administration

  Predose through 24 hours after the first dose on Day 1.

• Comparison of Cmax and AUC0-24 after 150 mg single-dose and 75 mg BID split-dose administration

  Predose through 24 hours after the first dose on Day 1.

• Exposure after the second versus first 75 mg dose in the split-dose cohort

  Part A: Predose through 24 hours after the first dose on Day 1.

Study Arms (8)

Part A - Cohort 1: 75 mg single dose

EXPERIMENTAL

Eight participants will be randomized 3:1: 6 participants to a single oral 75 mg dose of ZE74-0282 and 2 participants to matching placebo on Day 1 under fasted conditions.

Drug: ZE74-0282-0001 or placebo

Part A - Cohort 2: nominal 150 mg single dose

EXPERIMENTAL

Eight participants will be randomized 3:1: 6 participants to the Safety Review Committee-confirmed oral ZE74-0282 dose (nominally 150 mg) and 2 participants to matching placebo on Day 1. Fasted or fed conditions will be selected based on Safety Review Committee review.

Drug: ZE74-0282-0001 or placebo

Part A - Cohort 2a: 75 mg BID split dose

EXPERIMENTAL

Eight participants will be randomized 3:1: 6 participants to ZE74-0282 and 2 participants to matching placebo. Two oral doses will be administered on Day 1: 75 mg at Hour 0 and 75 mg 12 hours (+/- 30 minutes) later, for a total daily dose of 150 mg.

Drug: ZE74-0282-0001 or placebo

Part A - Cohort 3: nominal 225 mg

EXPERIMENTAL

Eight participants will be randomized 3:1: 6 participants to ZE74-0282 and 2 participants to matching placebo. The Safety Review Committee will confirm the dose and whether it is administered once or as divided twice-daily doses on Day 1, and whether dosing is under fasted or fed conditions. The nominal dose level is 225 mg.

Drug: ZE74-0282-0001 or placebo

Part A - Cohort 4: nominal 300 mg

EXPERIMENTAL

Eight participants will be randomized 3:1: 6 participants to ZE74-0282 and 2 participants to matching placebo. The Safety Review Committee will confirm the dose and whether it is administered once or as divided twice-daily doses on Day 1, and whether dosing is under fasted or fed conditions. The nominal dose level is 300 mg.

Drug: ZE74-0282-0001 or placebo

Part A - Cohort 5: nominal 375 mg

EXPERIMENTAL

Eight participants will be randomized 3:1: 6 participants to ZE74-0282 and 2 participants to matching placebo. The Safety Review Committee will confirm the dose and whether it is administered once or as divided twice-daily doses on Day 1, and whether dosing is under fasted or fed conditions. The nominal dose level is 375 mg.

Drug: ZE74-0282-0001 or placebo

Part B - Cohort 6: 75 mg BID for 7 days

EXPERIMENTAL

Eight participants will be randomized 3:1: 6 participants to ZE74-0282 and 2 participants to matching placebo. Participants will receive 75 mg twice daily approximately 12 hours (+/- 30 minutes) apart on Days 1 through 6 and one 75 mg morning dose on Day 7, for a total of 13 doses.

Drug: ZE74-0282-0001 or placebo

Part B - Cohort 7: 150 mg BID for 7 days

EXPERIMENTAL

Eight participants will be randomized 3:1: 6 participants to ZE74-0282 and 2 participants to matching placebo. Participants will receive 150 mg twice daily approximately 12 hours (+/- 30 minutes) apart on Days 1 through 6 and one 150 mg morning dose on Day 7, for a total of 13 doses.

Drug: ZE74-0282-0001 or placebo

Interventions

ZE74-0282-0001 or placebo DRUG

The participant will receive ZE74-0282-0001 or placebo

Part A - Cohort 1: 75 mg single dose; Part A - Cohort 2: nominal 150 mg single dose; Part A - Cohort 2a: 75 mg BID split dose; Part A - Cohort 3: nominal 225 mg; Part A - Cohort 4: nominal 300 mg; Part A - Cohort 5: nominal 375 mg; Part B - Cohort 6: 75 mg BID for 7 days; Part B - Cohort 7: 150 mg BID for 7 days

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy volunteers will be included in the study if they satisfy all of the following criteria:
• Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
• Adult males and females, 18 to 55 years of age (inclusive) at Screening.
• Body mass index (BMI) ≥18.0 and ≤32.0 kg/m2, with a body weight ≤100 kg at Screening.
• Medically healthy (in the opinion of the PI or delegate), as determined by pre-study medical history, and without CS abnormalities including the following:
• Physical examination without any clinically relevant findings;
• Systolic blood pressure in the range of 90 to 160 mmHg and diastolic blood pressure in the range of 50 to 95 mmHg after resting for 5 minutes in a semi-supine or supine position.
• Pulse rate in the range of 45 to 100 beats per minute after 5 minutes resting in a semi-supine or supine position.
• Body temperature (tympanic), between 35.5°C and 37.7°C.
• Electrocardiogram without CS abnormalities including QTcF \<450 msec.
• Female volunteers:
• Must be of non childbearing potential i.e., surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy) at least 6 weeks before the screening visit or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle stimulating hormone \[FSH\] level consistent with postmenopausal status, per local laboratory guidelines), or
• If of childbearing potential, must:
• i. Have a negative pregnancy test at the screening visit and on admission to the study site on Day -1.
• ii. Agree not to attempt to become pregnant or donate ova from signing the ICF until at least 30 days after the last dose of study drug.

You may not qualify if:

• Healthy volunteers will be excluded from the study if there is evidence of any of the following at the screening visit or prior to dosing at the timepoint in the SoA:
• History of anaphylaxis or other significant allergy which, in the opinion of the PI (or delegate), would interfere with the volunteer's ability to participate in the study.
• History or presence of CS cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic, psychiatric, or neurological disease/disorder, including any acute illness, within the past 3 months determined by the PI (or delegate) to be clinically relevant.
• History of surgery or hospitalisation within 3 months prior to screening, or surgery planned during the study.
• Any history of malignant disease in the last 10 years (excludes surgically resected skin squamous cell or basal cell carcinoma with histopathologically-confirmed clear margins).
• Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia.
• History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death) or a known arrythmia.
• Presence or having sequelae of gastrointestinal, liver (including Gilbert's syndrome), kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
• Liver function test results elevated more than 1.5 fold above the ULN for gamma glutamyl transferase, bilirubin (total, conjugated and unconjugated), ALP, AST or ALT. Volunteers with ALP and/or ALT/AST above the limits specified may be included, at the discretion of the PI (or delegate), if the levels are unaccompanied by clinical signs and are determined to be normal variants.
• Estimated creatinine clearance \<60 mL/min using the Cockcroft-Gault formula or serum creatinine \>1.5 fold above the ULN.
• A history of or positive test results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibodies at the screening visit.
• Regular consumption of more than 10 standard alcoholic drinks/week and/or more than 4 standard alcoholic drinks on any one day, where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer \[4.9% Alc/Vol\], 100 mL wine \[12% Alc/Vol\], or 30 mL spirit \[40% Alc/Vol\]).
• Females who are breastfeeding or are planning to breastfeed from screening until 3 months after the dose of study drug (or 5 × half-lives, whichever is longer).
• Unable to swallow oral medication
• Use of any prescription or over-the-counter medication (including oral contraceptives herbal products, nutritional supplements, diet aids, vitamin supplements, minerals and hormone supplements) within 7 days or 5 half-lives of the medication (whichever is longer) prior to the dose of study drug, except the use of paracetamol doses of 500 mg up to every 6 hours or 2 g per day maximum for no more than 3 consecutive days in one week.

Sponsors & Collaborators

• Eilean Therapeutics AU Pty Ltd: lead

Study Sites (1)

Scientia Clinical Research Ltd.

Randwick, New South Wales, 2031, Australia

RECRUITING

MeSH Terms

Conditions

Primary Myelofibrosis; Polycythemia; Thrombocythemia, Essential; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Ekaterina Dokukina

CONTACT

+1 858 353 4108; kdokukina@eilenther.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants, the Principal Investigator, clinical personnel involved in participant care or clinical evaluation, and the Sponsor are blinded to assignment to ZE74-0282 or placebo. Designated pharmacy and other protocol-specified personnel may remain unblinded.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants are assigned to one protocol cohort and randomized to ZE74-0282 or placebo. Cohorts are opened sequentially based on Safety Review Committee review of blinded safety and available PK data.

Study Record Dates

• First Submitted: March 23, 2026
• First Posted: April 14, 2026
• Study Start: April 16, 2026
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: July 28, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)