Clinical trial NCT05552274: FTIH of ECC4703 in Healthy Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Non-alcoholic Steatohepatitis (NASH)
Lead sponsor: Eccogene
Sponsor class: INDUSTRY
First posted: 2022-09-23
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with adverse events, with abnormal laboratory test results, abnormal ECGs, abnormal vital signs, and abnormal physical examinations
timeFrame: SAD: Up to 8 days and MAD: Up to 21 days
Secondary outcomes:
measure: Pharmacokinetic Parameters: AUC0-24
timeFrame: SAD: Up to Day 8 and MAD: Up to Day 21.
measure: Pharmacokinetic Parameters: AUC0-tlast
timeFrame: SAD: Up to Day 8
measure: Pharmacokinetic Parameters: AUC0-tau
timeFrame: MAD: Up to Day 21.
measure: Pharmacokinetic Parameters: AUC0-infinity
timeFrame: SAD: Up to Day 8
measure: Pharmacokinetic Parameters: Cmax
timeFrame: SAD: Up to Day 8 and MAD: Up to Day 21.
measure: Pharmacokinetic Parameters: C24
timeFrame: SAD: Up to Day 8 and MAD: Up to Day 21.
measure: Pharmacokinetic Parameters: Ctau
timeFrame: MAD: Up to Day 21.
measure: Pharmacokinetic Parameters: tmax
timeFrame: SAD: Up to Day 8 and MAD: Up to Day 21.
measure: Pharmacokinetic Parameters: tlag
timeFrame: SAD: Up to Day 8 and MAD: Up to Day 21.
measure: Pharmacokinetic Parameters: t1/2
timeFrame: SAD: Up to Day 8 and MAD: Up to Day 21.
measure: Pharmacokinetic Parameters: Clast
timeFrame: SAD: Up to Day 8
measure: Pharmacokinetic Parameters: tlast
timeFrame: SAD: Up to Day 8
measure: Pharmacokinetic Parameters: CL/F
timeFrame: SAD: Up to Day 8 and MAD: Up to Day 21.
measure: Pharmacodynamic assessment: LDL-C
timeFrame: SAD: Up to Day 8
measure: Pharmacodynamic assessment: HDL-C
timeFrame: MAD: Up to Day 21.
measure: Pharmacodynamic assessment: TG
timeFrame: MAD: Up to Day 21.
measure: Pharmacodynamic assessment: TC
timeFrame: MAD: Up to Day 21.
measure: Pharmacodynamic assessment: LDL
timeFrame: MAD: Up to Day 21.
measure: Pharmacodynamic assessment: VLDL
timeFrame: MAD: Up to Day 21.
measure: Pharmacodynamic assessment: ApoB
timeFrame: SAD: Up to Day 8 and MAD: Up to Day 21.
measure: Pharmacodynamic assessment: Lp(a)
timeFrame: MAD: Up to Day 21.
measure: Pharmacodynamic assessment: Glucose
timeFrame: MAD: Up to Day 21.
measure: Pharmacodynamic assessment: Serum Insulin
timeFrame: MAD: Up to Day 21.
measure: Thyroid function assessment: TT3
timeFrame: SAD: Up to Day 8 and MAD: Up to Day 21.
measure: Thyroid function assessment: FT3
timeFrame: SAD: Up to Day 8 and MAD: Up to Day 21.
measure: Thyroid function assessment: TT4
timeFrame: SAD: Up to Day 8 and MAD: Up to Day 21.
measure: Thyroid function assessment: FT4
timeFrame: SAD: Up to Day 8 and MAD: Up to Day 21.
measure: Thyroid function assessment: TSH
timeFrame: SAD: Up to Day 8 and MAD: Up to Day 21.
Other outcomes:
Locations:
city: Las Vegas
country: United States
facility: Eccogene Investigational Site
state: Nevada
Study officials:
affiliation: Eccogene Clinical Trials
name: Eccogene
role: STUDY_DIRECTOR
References: