FTIH of ECC4703 in Healthy Volunteers

Non-alcoholic Steatohepatitis (NASH) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05552274
• Other study ID #: EC0002
• Status: Recruiting
• Phase: Early Phase 1
• Start date: August 16, 2022
• Est. completion date: July 5, 2023

Study information

• Verified date: September 2022
• Source: Eccogene
• Contact: Eccogene Clinical Trials
• Phone: 86-21-61053022
• Email: contact[@]eccogene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 54
• Est. completion date: July 5, 2023
• Est. primary completion date: July 5, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fatty Liver
• Non-alcoholic Fatty Liver Disease
• Non-alcoholic Steatohepatitis (NASH)

Intervention

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
Matching Placebo will be administered as oral capsules. Matching Placebo will be given orally during each dosing day.

Locations

Country	Name	City	State
United States	Eccogene Investigational Site	Las Vegas	Nevada

Sponsors (1)

Lead Sponsor	Collaborator
Eccogene

Country where clinical trial is conducted

United States, 

Outcome

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