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

Phase 1
Completed
Conditions
Healthy
Interventions
Drug: ENC1018 for SAD
Drug: Placebo for SAD
Drug: ENC1018 for MAD
Drug: Placebo for MAD
Registration Number
NCT06224400
Lead Sponsor
EnnovaBio Australia Pharmaceuticals Pty Ltd
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
72
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ENC1018 for SADENC1018 for SAD6 of out 8 subjects per cohort will be randomized to receive ENC1018
Placebo for SADPlacebo for SAD2 of out 8 subjects per cohort will be randomized to receive placebo
ENC1018 for MADENC1018 for MAD6 of out 8 subjects per cohort will be randomized to receive ENC1018
Placebo for MADPlacebo for MAD2 of out 8 subjects per cohort will be randomized to receive placebo
Primary Outcome Measures
NameTimeMethod
Severity of TEAEs following ENC1018 administration will be assessed using categories as mild, moderate and severeDay 1 through Day 8 (SAD) or 21 (MAD)
Evaluations of clinical laboratory and changes from baseline will be assessed using descriptive statistics following ENC1018 administrationDay 1 through Day 8 (SAD) or 21 (MAD)

Laboratory values include hematology, biochemistry, clinical chemistry, coagulation, and urinalysis

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)
Evaluations of physical examinations and changes from baseline will be assessed using descriptive statistics following ENC1018 administrationDay 1 through Day 8 (SAD) or 21 (MAD)

Physical examination include assessments of the skin, cardiovascular, respiratory, gastrointestinal, and neurological systems

Evaluations of vital signs and changes from baseline will be assessed using descriptive statistics following ENC1018 administrationDay 1 through Day 8 (SAD) or 21 (MAD)

Vital signs include body temperature, respiratory rate, blood pressure, and pulse

Evaluations of 12-lead ECGs and changes from baseline will be assessed using descriptive statistics following ENC1018 administrationDay 1 through Day 8 (SAD) or 21 (MAD)

ECG parameters include heart rate, PR interval, QRS duration, QT interval, and QTcF interval

Secondary Outcome Measures
NameTimeMethod
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
Maximum plasma concentration (Cmax)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
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
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

Trial Locations

Locations (1)

Nucleus Network Pty Ltd.

🇦🇺

Melbourne, Victoria, Australia

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