FTIH of ECC4703 in Healthy Volunteers

A Randomized, Double-Blind, Placebo-Controlled, Single and Repeated Dose Escalation, FTIH Study to Investigate the Safety, Tolerability, PK and PD of ECC4703 in Healthy Volunteers and Participants With Treatment-Unnecessary LDL-C Under 160 mg/dL

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

Study Overview

• Status: Recruiting
• Conditions: Non-alcoholic Steatohepatitis (NASH)
• Intervention / Treatment: Drug: Placebo; Drug: ECC4703

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 Type: Interventional
• Enrollment (Anticipated): 54
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Eccogene Clinical Trials; Phone Number: 86-21-61053022; Email: contact@eccogene.com

Study Locations

• United States
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • Recruiting
      • Eccogene Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: SAD Cohorts 1 to 2: Participants receiving Placebo; Participants in each SAD cohort will be randomized to receive placebo	Drug: Placebo; Matching Placebo will be administered as oral capsules. Matching Placebo will be given orally during each dosing day.
Experimental: SAD Cohorts 1 to 2: Participants receiving 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).	Drug: ECC4703; ECC4703 will be administered as 1 mg, 10 mg and 40 mg capsules. ECC4703 will be administered as oral capsules during each dosing day.
Placebo Comparator: MAD Cohorts 1 to 4: Participants receiving Placebo; Participants will be randomized to receive a once-daily dose of placebo for 14 days.	Drug: Placebo; Matching Placebo will be administered as oral capsules. Matching Placebo will be given orally during each dosing day.
Experimental: MAD Cohorts 1 to 4: Participants receiving 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.	Drug: ECC4703; ECC4703 will be administered as 1 mg, 10 mg and 40 mg capsules. ECC4703 will be administered as oral capsules during each dosing day.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Eccogene
• Investigators: Study Director: Eccogene, Eccogene Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2022
• Primary Completion (Anticipated): July 5, 2023
• Study Completion (Anticipated): July 5, 2023

Study Registration Dates

• First Submitted: September 13, 2022
• First Submitted That Met QC Criteria: September 20, 2022
• First Posted (Actual): September 23, 2022

Study Record Updates

• Last Update Posted (Actual): September 23, 2022
• Last Update Submitted That Met QC Criteria: September 20, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: EC0002

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: Yes
• Studies a U.S. FDA-regulated device product: No