A First-in-Human SAD/MAD Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ENC1018 in Healthy Adult Subjects

A Phase 1, First-in-Human, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Escalating Single and Multiple Doses of ENC1018 in Healthy Adult Subjects

This is a Phase 1, FIH, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and PK characteristics of ENC1018 after single and multiple oral dose administration in healthy adult subjects.

The study will be conducted in two parts: Part A -Single ascending Dose (SAD) and Part B - Multiple ascending dose (MAD). A Food Effect Cohort will be conducted within Part A. Part A is for the single dose use of IP, while Part B is once daily use for 14 consecutive days.

Approximately 72 healthy adult subjects are planned to be enrolled. Each subject will be enrolled in only one cohort of either Parts A or B of the study, to receive only one dose regimen during the study. Part B may be initiated in parallel or prior to completion of Part A, at the discretion of Safety Review Committee (SRC), upon reviewing safety and plasma PK data.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: ENC1018 for SAD; Drug: Placebo for SAD; Drug: ENC1018 for MAD; Drug: Placebo for MAD

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Nucleus Network Pty Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male and female subjects of any ethnic origin, must be between 18 and 55 years of age inclusive.
• Subject is in generally good health according to the Investigator's assessment as determined by medical history, physical examination, vital sign assessment, 12-lead ECG, and clinical laboratory evaluations.
• Subject has a negative urine drug screen, cotinine screen, and alcohol breath test.
• Nonsmoker
• Subject has Body Mass Index 18.0 to 32.0 kg/m2 inclusive, and body weight from 50 - 100 kg for male subjects, 45 -100 kg for female subjects
• Apply contraception methods for child-bearing potential subjects.

Exclusion Criteria:

• Have clinically relevant medical history or unstable hepatic, pulmonary, hematologicalor immunological disease making implementation of the protocol or interpretation of the study results difficult, or that would put the subject at risk by participating in the study, under the discretion of the Investigator.
• Any disease or surgical procedure (including cholecystectomy) that may substantially affect IP absorption, distribution, metabolism, and excretion as judged by the Investigator
• Any current active infections, including localized infections, or any recent history (within 1 week prior to IP administration) of active infections, cough, or fever; or a history of recurrent or chronic infections.
• Dosing with any other investigational drug or therapy within 90 days prior to dosing.
• Is positive for HBsAg,HCVAb, HIVAb, or tuberculosis.
• Pregnant, breast-feeding and/or lactating women
• Have received any live vaccines (bacterial or viral) within 12 weeks prior to Screening or intend to receive a live vaccine during the study period or within 30 days after the last dose of the IP.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo for SAD; 2 of out 8 subjects per cohort will be randomized to receive placebo	Drug: Placebo for SAD; SAD: Healthy subjects meeting eligibility criteria will be sequentially randomized to each dose cohort (cohort A1-A6) to receive either ENC1018 or placebo. The investigational product (ENC1018 or placebo) will be administered orally as a single dose.
Placebo Comparator: Placebo for MAD; 2 of out 8 subjects per cohort will be randomized to receive placebo	Drug: Placebo for MAD; MAD: Healthy subjects meeting eligibility criteria will be sequentially randomized to each dose cohort (cohort B1-B3) to receive either ENC1018 or placebo. The investigational product (ENC1018 or placebo) will be administered orally for a total of 14 days.
Experimental: ENC1018 for SAD; 6 of out 8 subjects per cohort will be randomized to receive ENC1018	Drug: ENC1018 for SAD; SAD: Healthy subjects meeting eligibility criteria will be sequentially randomized to each dose cohort (cohort A1-A6) to receive either ENC1018 or placebo. The investigational product (ENC1018 or placebo) will be administered orally as a single dose.
Experimental: ENC1018 for MAD; 6 of out 8 subjects per cohort will be randomized to receive ENC1018	Drug: ENC1018 for MAD; MAD: Healthy subjects meeting eligibility criteria will be sequentially randomized to each dose cohort (cohort B1-B3) to receive either ENC1018 or placebo. The investigational product (ENC1018 or placebo) will be administered orally for a total of 14 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and type of treatment emergent adverse events (TEAE) following ENC1018 administration will be assessed using the latest version of Medical Dictionary for Regulatory Activities (MedDRA 25.0 or above)		Day 1 through Day 8 (SAD) or 21 (MAD)
Severity of TEAEs following ENC1018 administration will be assessed using categories as mild, moderate and severe		Day 1 through Day 8 (SAD) or 21 (MAD)
Evaluations of clinical laboratory and changes from baseline will be assessed using descriptive statistics following ENC1018 administration	Laboratory values include hematology, biochemistry, clinical chemistry, coagulation, and urinalysis	Day 1 through Day 8 (SAD) or 21 (MAD)
Evaluations of physical examinations and changes from baseline will be assessed using descriptive statistics following ENC1018 administration	Physical examination include assessments of the skin, cardiovascular, respiratory, gastrointestinal, and neurological systems	Day 1 through Day 8 (SAD) or 21 (MAD)
Evaluations of vital signs and changes from baseline will be assessed using descriptive statistics following ENC1018 administration	Vital signs include body temperature, respiratory rate, blood pressure, and pulse	Day 1 through Day 8 (SAD) or 21 (MAD)
Evaluations of 12-lead ECGs and changes from baseline will be assessed using descriptive statistics following ENC1018 administration	ECG parameters include heart rate, PR interval, QRS duration, QT interval, and QTcF interval	Day 1 through Day 8 (SAD) or 21 (MAD)

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum plasma concentration (Cmax)	SAD: Up to Day 4, 72 hours post dose; MAD: up to Day 17, 72 hours post last dose
Area under the plasma concentration versus time curve (AUC)	SAD: Up to Day 4, 72 hours post dose; MAD: up to Day 17, 72 hours post last dose
Time to maximum concentration (Tmax)	SAD: Up to Day 4, 72 hours post dose; MAD: up to Day 17, 72 hours post last dose
Terminal elimination half-life (t1/2)	SAD: Up to Day 4, 72 hours post dose; MAD: up to Day 17, 72 hours post last dose
Apparent oral plasma clearance (CL/F)	SAD: Up to Day 4, 72 hours post dose; MAD: up to Day 17, 72 hours post last dose
Apparent volume of distribution during the terminal phase (Vz/F)	SAD: Up to Day 4, 72 hours post dose; MAD: up to Day 17, 72 hours post last dose

Collaborators and Investigators

• Sponsor: EnnovaBio Australia Pharmaceuticals Pty Ltd
• Investigators: Principal Investigator: Philip Ryan, Doctor, Nucleus Network Pty Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2024
• Primary Completion (Actual): September 9, 2024
• Study Completion (Actual): April 15, 2025

Study Registration Dates

• First Submitted: January 8, 2024
• First Submitted That Met QC Criteria: January 17, 2024
• First Posted (Actual): January 25, 2024

Study Record Updates

• Last Update Posted (Actual): April 25, 2025
• Last Update Submitted That Met QC Criteria: April 24, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: ENC1018-P1-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No