A First-in-Human Study of ZE66-0205 in Healthy Volunteers

NCT07735728 | Not Yet Recruiting Phase 1

• 1 other identifier: ZE66-0205-0001
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This first-in-human study will evaluate ZE66-0205 in healthy adults. The main purpose is to assess the safety and tolerability of single oral doses and, if evaluated, two doses given on Day 1. The study will also assess how ZE66-0205 is absorbed, distributed, and eliminated from the body and how it affects MALT1 levels in blood cells. Participants will be assigned by chance to receive ZE66-0205 or placebo in sequential ascending-dose cohorts.

Conditions

Healthy Volunteers (HV)

Keywords

ZE66-0205; MALT1; MALT1 degrader; proteolysis-targeting chimera; PROTAC; first-in-human; single ascending dose; pharmacokinetics; pharmacodynamics

Outcome Measures

Primary Outcomes (9)

• Incidence of treatment-emergent adverse events (TEAEs)

  Number and percentage of participants with one or more TEAEs. Events will be summarised by severity and relationship to study drug; adverse events leading to withdrawal will also be reported.

  From the first dose on Day 1 through the End-of-Study visit on Day 8 (±1 day)

• Incidence of serious adverse events (SAEs)

  Number and percentage of participants with one or more SAEs, including severity and relationship to study drug.

  From the first dose on Day 1 through the End-of-Study visit on Day 8 (±1 day)

• Change from Baseline in body weight

  Observed body weight and change from the Day 1 pre-dose Baseline, measured in kilograms.

  Baseline to Day 8 (±1 day)

• Change from Baseline in systolic and diastolic blood pressure

  Observed values and changes from the Day 1 pre-dose Baseline in systolic and diastolic blood pressure, measured in mmHg.

  Baseline through Day 8 (±1 day)

• Change from Baseline in pulse rate

  Observed pulse rate and change from the Day 1 pre-dose Baseline, measured in beats per minute.

  Baseline through Day 8 (±1 day)

• Change from Baseline in respiratory rate

  Observed respiratory rate and change from the Day 1 pre-dose Baseline, measured in breaths per minute.

  Baseline through Day 8 (±1 day)

• Change from Baseline in body temperature

  Observed body temperature and change from the Day 1 pre-dose Baseline, measured in degrees Celsius.

  Baseline through Day 8 (±1 day)

• Change from Baseline in electrocardiogram parameters

  Observed values and changes from the Day 1 pre-dose Baseline in ventricular heart rate, PR interval, QRS duration, QT interval, and QT interval corrected using Fridericia's formula (QTcF).

  Baseline through Day 8 (±1 day)

• Participants with clinically significant post-Baseline clinical laboratory abnormalities

  Number and percentage of participants with clinically significant abnormalities in haematology, clinical chemistry, coagulation, or urinalysis. Observed values and changes from the Day 1 pre-dose Baseline will also be summarised.

  Baseline through Day 8 (±1 day)

Secondary Outcomes (9)

• Maximum observed plasma concentration (Cmax) of ZE66-0205

  Pre-dose through 168 hours post-dose

• Time to maximum observed plasma concentration (Tmax) of ZE66-0205

  Pre-dose through 168 hours post-dose

• Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC0-last)

  Pre-dose through 168 hours post-dose

• Area under the plasma concentration-time curve from time 0 to 24 hours (AUC0-24)

  Pre-dose through 24 hours post-dose

• Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC0-inf)

  Pre-dose through 168 hours post-dose

Other Outcomes (2)

• Change from Baseline in MALT1 level in peripheral blood mononuclear cells (PBMCs)

  Screening and pre-dose through 168 hours post-dose

• Relationship between ZE66-0205 plasma concentrations and MALT1 levels in PBMCs

  Pre-dose through 168 hours post-dose

Study Arms (5)

Placebo

PLACEBO COMPARATOR

Matching placebo. Two participants in each planned cohort will receive placebo capsules that match ZE66-0205 in appearance. Placebo will be administered orally under the same dosing and meal conditions as the corresponding active cohort. If twice-daily dosing is evaluated, placebo participants will receive a second dose approximately 12 hours after the first dose.

Drug: Placebo

Experimental: Cohort 1

EXPERIMENTAL

ZE66-0205 50 mg. Six participants will receive a single oral 50 mg dose on Day 1 under fasted conditions.

Drug: ZE66-0205

Experimental: Cohort 2

EXPERIMENTAL

ZE66-0205 nominal 100 mg. Six participants will receive the SRC-confirmed oral dose on Day 1. The nominal dose is 100 mg; the actual dose may be adjusted based on emerging safety, PK, and PD data. Fed conditions or twice-daily dosing may be evaluated if selected by the SRC.

Drug: ZE66-0205

Experimental: Cohort 3

EXPERIMENTAL

ZE66-0205 nominal 200 mg. Six participants will receive the SRC-confirmed oral dose on Day 1. The nominal dose is 200 mg; the actual dose may be adjusted based on emerging safety, PK, and PD data. Fed conditions or twice-daily dosing may be evaluated if selected by the SRC.

Drug: ZE66-0205

Experimental: Cohort 4

EXPERIMENTAL

ZE66-0205 nominal 300 mg. Six participants will receive the SRC-confirmed oral dose on Day 1. The nominal dose is 300 mg; the actual dose may be adjusted based on emerging safety, PK, and PD data. Fed conditions or twice-daily dosing may be evaluated if selected by the SRC.

Drug: ZE66-0205

Interventions

ZE66-0205 DRUG

ZE66-0205 oral soft gelatin capsules, 50 mg strength. Participants will receive the assigned total dose orally with approximately 240 mL of water. Planned nominal single-dose levels are 50 mg, 100 mg, 200 mg, and 300 mg. If twice-daily dosing is evaluated, a second dose will be administered approximately 12 hours after the morning dose.

Experimental: Cohort 1; Experimental: Cohort 2; Experimental: Cohort 3; Experimental: Cohort 4

Placebo DRUG

Placebo formulation not containing the active drug

Placebo

Eligibility Criteria

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

You may qualify if:

• Written informed consent provided before any study-related activities; able to understand the nature, purpose, risks, and possible adverse effects of the study.
• Male or female, 18 to 55 years of age, inclusive, at Screening.
• Body mass index 18.0 to 32.0 kg/m², inclusive, and body weight no more than 100 kg at Screening.
• Medically healthy in the opinion of the Investigator or delegate based on medical history and absence of clinically significant abnormalities, including: no clinically relevant physical-examination findings; systolic blood pressure 90 to 160 mmHg and diastolic blood pressure 50 to 95 mmHg after at least 5 minutes of rest; pulse rate 40 to 100 beats/minute after at least 5 minutes of rest; tympanic body temperature 35.5°C to 37.7°C; and electrocardiogram without clinically significant abnormalities, including QTcF less than 450 msec for males and less than 470 msec for females.
• Female participants must be of non-childbearing potential (surgically sterilised at least 6 weeks before Screening or postmenopausal with confirmatory follicle-stimulating hormone level) or, if of childbearing potential, must have negative pregnancy tests at Screening and Day -1, agree not to become pregnant or donate ova until at least 30 days after the last dose, and use protocol-defined adequate contraception during this period unless exclusively in a same-sex relationship or abstinent as a committed lifestyle.
• Male participants must agree not to donate sperm until at least 90 days after the last dose. When engaging in sexual intercourse with a female partner who could become pregnant, the participant must use a condom together with a protocol-defined highly effective method of contraception until at least 90 days after the last dose. When engaging in sexual intercourse with a female partner who is not of childbearing potential or with a same-sex partner, the participant must use a condom until at least 5 days after the last dose.
• Suitable venous access for blood sampling.
• Willing and able to comply with all study assessments, schedule requirements, and restrictions.

You may not qualify if:

• History of anaphylaxis or another significant allergy that, in the opinion of the Investigator or delegate, could interfere with study participation.
• History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, psychiatric, or neurological disease or disorder, including any clinically relevant acute illness within the previous 3 months.
• Surgery or hospitalization within 3 months before Screening, or planned surgery during the study.
• History of malignant disease within the previous 10 years, except surgically resected squamous-cell or basal-cell skin carcinoma with histopathologically confirmed clear margins.
• Clinically relevant immunosuppression, including immunodeficiency conditions such as common variable hypogammaglobulinemia.
• History of risk factors for torsade de pointes, including family history of long QT syndrome or sudden cardiac death, or a known arrhythmia.
• Gastrointestinal, hepatic (including Gilbert syndrome), renal, or other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Gamma-glutamyl transferase, total bilirubin, alkaline phosphatase, aspartate aminotransferase, or alanine aminotransferase greater than 1.5 times the upper limit of normal, unless an isolated elevation is considered a normal variant by the Investigator or delegate and is not accompanied by clinical signs.
• Estimated creatinine clearance below 60 mL/min using the Cockcroft-Gault formula or serum creatinine greater than 1.5 times the upper limit of normal.
• History of or positive Screening test for human immunodeficiency virus, hepatitis B surface antigen, or hepatitis C virus antibodies.
• Positive urine drug-of-abuse test, carbon monoxide breath test, or alcohol breath test at Screening or Day -1.
• Regular smoking of more than 5 cigarettes per week or equivalent, including tobacco, nicotine replacement therapy, e-cigarettes, or marijuana. Casual smokers may be eligible only if all protocol requirements are met.
• Pregnant or breastfeeding female, or female planning to breastfeed from Screening until 3 months after the last dose or 5 half-lives, whichever is longer.
• Unable to swallow oral medication.
• Use of prescription medication, including oral contraceptives, within 14 days or 5 half-lives, whichever is longer, before the first dose; or use of over-the-counter medication within 7 days or 5 half-lives, whichever is longer, before the first dose, except protocol-permitted paracetamol.

Sponsors & Collaborators

• Eilean Therapeutics: lead

Study Sites (1)

Scientia Clinical Research Ltd

Randwick, New South Wales, 2031, Australia

Location

Study Officials

• Ekaterina Dokukina

  Eilean Therapeutics AU Pty Ltd

  STUDY DIRECTOR

Central Study Contacts

Ekaterina Dokukina, MD

CONTACT

+1 858 353 4108; kdokukina@eilenther.com

Carlo Cervi

CONTACT

ccervi@diagenta.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants, the Sponsor, the Principal Investigator, and clinical study personnel involved in participant care or clinical evaluations will be blinded to treatment assignment. The randomisation statistician, designated unblinded pharmacy staff, unblinded study monitor, bioanalytical laboratory, and unblinded pharmacokineticist performing interim PK analyses will be unblinded. Data provided to the Safety Review Committee will be blinded.
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Sequential dose-escalation cohorts will be evaluated from lower to higher dose levels. Within each cohort, participants will be randomized in a 3:1 ratio to ZE66-0205 or matching placebo

Study Record Dates

• First Submitted: July 24, 2026
• First Posted: July 30, 2026
• Study Start (Estimated): August 15, 2026
• Primary Completion (Estimated): August 15, 2027
• Study Completion (Estimated): August 15, 2027
• Last Updated: July 30, 2026

Record last verified: 2026-07

Locations

AU (1)