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

NCT06224400 | Completed Phase 1

• 1 other identifier: ENC1018-P1-01
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (6)

• 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

Study Arms (4)

ENC1018 for SAD

EXPERIMENTAL

6 of out 8 subjects per cohort will be randomized to receive ENC1018

Drug: ENC1018 for SAD

Placebo for SAD

PLACEBO COMPARATOR

2 of out 8 subjects per cohort will be randomized to receive placebo

Drug: Placebo for SAD

ENC1018 for MAD

EXPERIMENTAL

6 of out 8 subjects per cohort will be randomized to receive ENC1018

Drug: ENC1018 for MAD

Placebo for MAD

PLACEBO COMPARATOR

2 of out 8 subjects per cohort will be randomized to receive placebo

Drug: Placebo for MAD

Interventions

ENC1018 for SAD DRUG

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.

ENC1018 for SAD

Placebo for SAD DRUG

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 for SAD

ENC1018 for MAD DRUG

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.

ENC1018 for MAD

Placebo for MAD DRUG

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.

Placebo for MAD

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• EnnovaBio Australia Pharmaceuticals Pty Ltd: lead

Study Sites (1)

Nucleus Network Pty Ltd.

Melbourne, Victoria, 3004, Australia

Location

MeSH Terms

Interventions

Sagittal Abdominal Diameter; mycophenolic adenine dinucleotide

Intervention Hierarchy (Ancestors)

Body Size; Body Weights and Measures; Body Constitution; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Anthropometry; Investigative Techniques; Physiological Phenomena

Study Officials

• Philip Ryan, Doctor

  Nucleus Network Pty Ltd.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2024
• First Posted: January 25, 2024
• Study Start: March 5, 2024
• Primary Completion: September 9, 2024
• Study Completion: April 15, 2025
• Last Updated: April 25, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)