FTIH of ECC4703 in Healthy Volunteers

Early Phase 1

Completed

• Conditions: Non-alcoholic Steatohepatitis (NASH)
• Interventions: Drug: ECC4703; Drug: Placebo

• Registration Number: NCT05552274
• Lead Sponsor: Eccogene

Brief Summary

This is a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose and multiple ascending dose study of ECC4703 in healthy volunteers and participants with treatment unnecessary LDL-C under 160 mg/dL

Detailed Description

This study will be conducted in two cohorts of Single Ascending Dose (SAD) with a dose range from 1mg to 400mg and in four cohorts of Multiple Ascending Dose (MAD) with a dose range of 40mg to 160mg to Investigate the Safety, Tolerability, PK, and PD of ECC4703 in Healthy Volunteers and Participants with Treatment Unnecessary LDL-C under 160 mg/dL

Study Timeline

• Study Start: 2022-08-16
• Study First Submitted: 2022-09-13
• Study First Submitted QC: 2022-09-20
• Study First Posted: 2022-09-23
• Primary Completion: 2023-10-26
• Study Completion: 2023-10-26
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-02
• Last Update Posted: 2024-07-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 75

Inclusion Criteria

• Healthy male and female participants of any ethnic origin
• Age of 18 to 65 years
• BMI of 18.0 to 32.0 kg/m2
• Female participants who are postmenopausal, confirmed by FSH test, or surgically sterile, confirmed by medical documentation, or if they are of child bearing potential agree to use at least 1 highly effective method of contraception and 1 additional effective method at the same time, or agree to practice true abstinence
• Male participants agree to use contraception, or agree to practice true abstinence
• No clinically significant findings in physical examination, 12-lead electrocardiogram (ECG), vital sign measurements, laboratory tests, or medical/psychiatric history
• Not taking any medication on a regular basis
• Able to understand and sign and date informed consent

Additional Inclusion Criteria for Part 2 (MAD) Cohorts B2 to B4

• Fasting LDL-C ≥ 100 mg/dL and ≤ 159 mg/dL at screening
• Not eligible for lipid-lowering therapy (such as statin) as decided by the qualified clinician at screening based on <2019 ACC/AHA Guidelines on the Primary Prevention of Cardiovascular Disease>
• Hemoglobin A1c (HbA1c) ≤ 6.5%.

Exclusion Criteria

• Females who are pregnant including a positive result of pregnancy test, planning to become pregnant, or breastfeeding.
• History of febrile illness or evidence of active infection within 14 days prior to the first dose of study;
• Use of any concomitant medication
• History of drug abuse or alcohol abuse within the past 5 years;
• Regular use of tobacco, nicotine or tobacco products within the past 6 months of the study ;
• Unwilling to abstain from alcohol containing products and/or xanthine/caffeine containing products, including any food and beverages, within 48 h prior to the first dose of study drug;
• Concomitant participation in any investigational study of any nature
• Blood loss of non-physiological reasons ≥ 200 ml (i.e. trauma, blood collection, blood donation) within 2 months prior to the first dose of study drug, or plan to donate blood during this trial and within 1 month after the last dosing;
• Abnormal renal function estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m2
• Currently diagnosed type 2 diabetes mellitus (T2DM) or has history of T2DM.
• Significant allergic reaction to active ingredients or excipients of the study drug.
• Any clinically significant abnormal findings in the participant's physical examination, laboratory tests, pregnancy test, urine drug screen, alcohol test, or medical history which in the opinion of the Investigator would prevent the participants from participating in the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SAD Cohorts 1 to 2: Participants receiving ECC4703	ECC4703	Participants in each SAD cohort will be randomized to receive up to 4 escalating doses (1 mg, 4 mg, 12 mg, 32 mg, 80 mg, 160 mg, 320 mg or 400 mg).
MAD Cohorts 1 to 4: Participants receiving Placebo	Placebo	Participants will be randomized to receive a once-daily dose of placebo for 14 days.
MAD Cohorts 1 to 4: Participants receiving ECC4703	ECC4703	Participants will be randomized to receive a once-daily dose of 1 of 3 escalating doses (40 mg, 80 mg, or 160 mg) for 14 days.
SAD Cohorts 1 to 2: Participants receiving Placebo	Placebo	Participants in each SAD cohort will be randomized to receive placebo

Primary Outcome Measures

Name	Time	Method
Number of participants with adverse events, with abnormal laboratory test results, abnormal ECGs, abnormal vital signs, and abnormal physical examinations	SAD: Up to 8 days and MAD: Up to 21 days	Safety Assessment evaluated through adverse events, laboratory evaluations, vital signs, ECGs, and physical examination.

Secondary Outcome Measures

Name	Time	Method
Pharmacodynamic assessment: HDL-C	MAD: Up to Day 21.	Measurement of High Density Lipoprotein Cholesterol
Pharmacodynamic assessment: VLDL	MAD: Up to Day 21.	Measurement of Very Low Density Lipoprotein
Pharmacokinetic Parameters: AUC0-tau	MAD: Up to Day 21.	AUC over a dosing interval from time 0 to time of last quantifiable concentration
Pharmacokinetic Parameters: AUC0-infinity	SAD: Up to Day 8	AUC from time 0 extrapolated to infinity
Pharmacokinetic Parameters: Cmax	SAD: Up to Day 8 and MAD: Up to Day 21.	Maximum observed plasma concentration
Pharmacokinetic Parameters: C24	SAD: Up to Day 8 and MAD: Up to Day 21.	Observed concentration at 24 hours post dose
Pharmacokinetic Parameters: Ctau	MAD: Up to Day 21.	Observed concentration at the end of the dosing interval
Pharmacokinetic Parameters: tmax	SAD: Up to Day 8 and MAD: Up to Day 21.	Time of the maximum observed plasma concentration
Pharmacodynamic assessment: ApoB	SAD: Up to Day 8 and MAD: Up to Day 21.	Measurement of Apolipoprotein B
Thyroid function assessment: FT3	SAD: Up to Day 8 and MAD: Up to Day 21.	Measurement of Free Triiodothyronine
Thyroid function assessment: TT4	SAD: Up to Day 8 and MAD: Up to Day 21.	Measurement of Total Thyroxine
Thyroid function assessment: FT4	SAD: Up to Day 8 and MAD: Up to Day 21.	Measurement of Free Thyroxine
Thyroid function assessment: TSH	SAD: Up to Day 8 and MAD: Up to Day 21.	Measurement of Thyroid Stimulating Hormone
Pharmacokinetic Parameters: AUC0-tlast	SAD: Up to Day 8	AUC from time 0 to the time of last quantifiable non-zero concentration
Pharmacodynamic assessment: LDL-C	SAD: Up to Day 8	Measurement of Low Density Lipoprotein Cholesterol
Pharmacodynamic assessment: TC	MAD: Up to Day 21.	Measurement of Total Cholesterol
Pharmacodynamic assessment: Glucose	MAD: Up to Day 21.	Measurement of Glucose
Pharmacokinetic Parameters: AUC0-24	SAD: Up to Day 8 and MAD: Up to Day 21.	AUC from time 0 to 24 hour dosing interval
Thyroid function assessment: TT3	SAD: Up to Day 8 and MAD: Up to Day 21.	Measurement of Total Triiodothyronine
Pharmacokinetic Parameters: tlag	SAD: Up to Day 8 and MAD: Up to Day 21.	Lag time (time delay between dosing and first observed plasma concentration)
Pharmacokinetic Parameters: t1/2	SAD: Up to Day 8 and MAD: Up to Day 21.	Apparent terminal elimination half-life
Pharmacokinetic Parameters: Clast	SAD: Up to Day 8	Last measurable non-zero concentration
Pharmacokinetic Parameters: CL/F	SAD: Up to Day 8 and MAD: Up to Day 21.	Apparent Clearance
Pharmacodynamic assessment: LDL	MAD: Up to Day 21.	Measurement of Low Density Lipoprotein
Pharmacokinetic Parameters: tlast	SAD: Up to Day 8	Time of last measurable non-zero concentration
Pharmacodynamic assessment: TG	MAD: Up to Day 21.	Measurement of Triglycerides
Pharmacodynamic assessment: Lp(a)	MAD: Up to Day 21.	Measurement of Lipoprotein (a)
Pharmacodynamic assessment: Serum Insulin	MAD: Up to Day 21.	Measurement of Serum Insulin

Trial Locations

Locations (1)

Eccogene Investigational Site; 🇺🇸 Las Vegas, Nevada, United States