Сlinical Study Aiming to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Ascending Doses of ZE63-0302 in Healthy Volunteers

NCT06780124 | Completed Phase 1 DMC

• 1 other identifier: ZE63-0302-0001
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 1

Brief Summary

A first-in-human study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple ascending doses of ZE63-0302 administered orally in healthy volunteers.

Conditions

Healthy

Keywords

Acute leukemia; Acute KMTRAR mutated myeloid leukemia; Acute NPM1 mutated myeloid leukemia

Outcome Measures

Primary Outcomes (2)

• Plasma pharmacokinetics of ZE63-0302

  Plasma concentration, ng/mL

  Within 15 min prior to dosing with ZE63-0302/placebo to 168 hours post-dose for SAD . Within 15 min prior to dosing with ZE63-0302/placebo to 264 hours post-dose for MAD.

• Effect of BMI on the PK of ZE63-0302 in plasma following administration of single oral doses (for dose levels 5 and 6 only)

  Plasma concentration, ng/mL

  Within 15 min prior to dosing with ZE63-0302/placebo to 168 h post-dose.

Secondary Outcomes (1)

• Incidence of adverse events (AEs)

  From the signing of the consent form until day 8 for SAD dose levels 1-5 and 7 and until day 11 for SAD dose level 6 and until day 18 for MAD.

Study Arms (9)

Level 1 Single dose

EXPERIMENTAL

Dose level 1: 6 participants will receive 20 mg ZE63-0302 and 2 participants will receive placebo under fasted conditions.

Drug: ZE63-0302 or placebo

Level 2 Single dose

EXPERIMENTAL

Dose level 2: 6 participants will receive 100 mg ZE63-0302 and 2 participants will receive placebo under fasted conditions.

Drug: ZE63-0302 or placebo

Level 3 Single dose

EXPERIMENTAL

Dose level 3: 6 participants will receive 300 mg ZE63-0302 and 2 participants will receive placebo under fasted conditions.

Drug: ZE63-0302 or placebo

Level 4 Single dose

EXPERIMENTAL

Dose level 4: 6 participants will receive 600 mg ZE63-0302 and 2 participants will receive placebo under fasted conditions.

Drug: ZE63-0302 or placebo

Level 5 Single dose

EXPERIMENTAL

Dose level 5: 9 participants will receive 300 mg ZE63-0302 and 3 participants will receive placebo under fed conditions.

Drug: ZE63-0302 or placebo

Level 6 Single dose

EXPERIMENTAL

Dose level 6: 6 participants will receive 600 mg ZE63-0302 plus itraconazole and 2 participants will receive placebo plus itraconazole under fasted conditions.

Drug: ZE63-0302 or placebo

Level 7 Single dose

EXPERIMENTAL

Dose level 7: 3 participants will receive 600 mg ZE63-0302 and 1 participant will receive placebo under fed conditions.

Drug: ZE63-0302 or placebo

Level 1 Multiple doses

EXPERIMENTAL

Dose level 1: 6 participants will receive 600 mg ZE63-0302 and 2 participants will receive placebo once daily under fasted and/or fed conditions. Duration of dosing (ZE63-0302 or placebo) is 7 days.

Drug: ZE63-0302 or placebo

Level 2 Multiple doses

EXPERIMENTAL

Dose level 2: 6 participants will receive 300 mg ZE63-0302 and 2 participants will receive placebo twice daily under fasted and/or fed conditions. Duration of dosing (ZE63-0302 or placebo) is 7 days.

Drug: ZE63-0302 or placebo

Interventions

ZE63-0302 or placebo DRUG

The participants will receive ZE63-0302 or placebo

Level 1 Multiple doses; Level 1 Single dose; Level 2 Multiple doses; Level 2 Single dose; Level 3 Single dose; Level 4 Single dose; Level 5 Single dose; Level 6 Single dose; Level 7 Single dose

Eligibility Criteria

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

You may qualify if:

• 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) ≥ 18.5 and ≤ 32.0 kg/m2, with a body weight (to 1 decimal place) ≥ 50.0 kg at screening, to be included in the main group for all SAD and MAD cohorts. BMI ≥ 30.0 and ≤ 35.0 kg/m2, with a body weight (to 1 decimal place) ≥ 50.0 kg at screening, to be included in the high BMI group for SAD Cohorts 5 and 7.
• Medically healthy without clinically significant abnormalities (in the opinion of the Investigator) at the screening visit and prior to dosing at the timepoints indicated in the SoA, including:
• Physical examination without any clinically significant findings.
• Systolic blood pressure in the range of 90 mm Hg to 140 mm Hg; diastolic blood pressure in the range of 40 mm Hg to 90 mm Hg.
• HR in the range of 40 to 100 bpm after at least 5 minutes in a supine position
• Body temperature (tympanic or oral) in the range 35.5°C to 37.5°C (inclusive).
• No clinically significant findings in serum chemistry, hematology, coagulation and urinalysis tests as judged by the Investigator. Note: for SAD Cohort 6, ALT, AST, ALP and gamma-glutamyl transferase (GGT) must be normal (within the reference range).
• Triplicate 12-lead ECG (taken after the volunteer has been supine for at least 5 minutes) with a QTcF ≤ 450 msec for males and ≤ 470 msec for females and no clinically significant abnormalities.
• Be nonsmokers (including tobacco, nicotine replacement therapy, e-cigarettes and marijuana) for at least 3 months prior to first study drug administration (self-reported to the Investigator) at screening visit, Day -4 (SAD Cohort 6 only) and at check-in on Day -1.
• Female volunteers must:
• Be of nonchildbearing potential i.e., surgically sterilized (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before screening) or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause, and a follicle-stimulating hormone (FSH) level \>40 IU/L at the screening visit), or
• If of childbearing potential, must agree not to donate ova, not to attempt to become pregnant and, if engaging in sexual intercourse with a male partner, must agree to use an acceptable method of contraception from one month prior to screening until at least 30 days after the last dose of study drug.
• Male volunteers must agree not to donate sperm and, if engaging in sexual intercourse with a female partner who could become pregnant, must agree to use an acceptable method of contraception from signing the consent form until at least 90 days after the last dose of study drug.

You may not qualify if:

• History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or major surgery within the past 3 months determined by the PI to be clinically significant.
• Acute infections or infestations within 4 weeks prior to dosing or current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications.
• Presence or history of any abnormality or illness, including gastrointestinal surgery, which in the opinion of the PI may affect absorption, distribution, metabolism or elimination of the study drug.
• Any history of malignant disease in the last 5 years (excludes surgically resected skin squamous cell or basal cell carcinoma).
• Any screening laboratory result outside the normal laboratory reference range (as confirmed upon repeated testing) and deemed clinically significant by the PI.
• Participants who have Gilbert's syndrome, or who have hyperbilirubinemia consistent with Gilbert's syndrome, will not be eligible.
• Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia.
• Use of or plans to use systemic immunosuppressive (e.g., corticosteroids by any route, methotrexate, azathioprine, cyclosporine) or immunomodulating medications (e.g., interferon) within 5 half-lives of individual agent or within 28 days (whichever is longer) prior to dosing or during the study.
• Use of or plans to use agents (e.g., grapefruit and grapefruit products) that have clinically significant interaction with CYP3A4 or the use of any medications that could have a significantly impact on organ function (e.g., barbiturates, omeprazole, cimetidine) during the study or within 5 half-lives of individual agent or within 28 days (whichever is longer) prior to dosing.
• History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death) or clinically significant arrythmia.
• Participant is planning to have surgery between Screening and the EoS visit.
• Positive test results for active human immunodeficiency virus (HIV-1 or HIV-2), hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies at the screening visit.
• Presence or having sequelae of gastrointestinal, liver, kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
• Estimated creatinine clearance \< 60 mL/min using the Cockcroft-Gault formula.
• History of any drug or alcohol abuse in the past 2 years defined as \>21 units of alcohol per week for males and \>14 units of alcohol per week for females. Where 1 unit = 360 mL of beer, 150 mL wine, or 30 mL of spirits.

Sponsors & Collaborators

• Eilean Therapeutics: lead

Study Sites (1)

Linear Clinical Research Ltd

Perth, Nedlands, WA6009, Australia

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2025
• First Posted: January 17, 2025
• Study Start: April 12, 2024
• Primary Completion: June 24, 2025
• Study Completion: November 7, 2025
• Last Updated: January 22, 2026

Record last verified: 2026-01

Locations

AU (1)