FTIH of ECC5004 in Healthy and Diabetic Participants

Phase 1

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: Placebo; Drug: ECC5004

• Registration Number: NCT05654831
• Lead Sponsor: Eccogene

Brief Summary

This is a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose and multiple ascending dose study of ECC5004 in healthy participants and in patients with Type 2 Diabetes Mellitus

Detailed Description

This study will be conducted in two cohorts of Single Ascending Dose (SAD) with a dose range from 1mg to 300mg, and in four cohorts of Multiple Ascending Dose (MAD) with a dose range of 10mg to 150mg to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ECC5004 in Healthy Participants and in Patients with Type 2 Diabetes Mellitus

Study Timeline

• Study Start: 2022-12-01
• Study First Submitted: 2022-12-08
• Study First Submitted QC: 2022-12-08
• Study First Posted: 2022-12-16
• Primary Completion: 2023-11-01
• Study Completion: 2023-11-01
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-15
• Last Update Posted: 2024-07-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 69

Inclusion Criteria

• Healthy male and female participants of non-childbearing potential
• Age of 18 to 65 years
• BMI of 18.0 to 32.0 kg/m2
• Hemoglobin A1c ≤ 6.0%
• Female participants who are postmenopausal, confirmed by FSH test, or surgically sterile, confirmed by medical documentation, 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
• Able to understand and sign and date informed consent

Additional Inclusion Criteria for Part 2 (MAD)

• Diagnosed Type 2 Diabetes Mellitus of 18 to 70 years of age inclusive
• Type 2 Diabetes Mellitus with lifestyle modification only or with stable dose of metformin for ≥ 2 months prior to the study treatment
• BMI of 24.0 to 40.0 kg/m2 with a minimum body weight of 50.0 kg (110 lbs)
• HbA1c ≥ 7.0% and ≤ 10.5%, and fasting plasma glucose ≤ 270 mg/dL
• Blood pressure (BP) with or without medication: Systolic BP ≤ 160 mmHg, AND Diastolic BP ≤ 100 mmHg
• Not taking any active treatment regimen

Exclusion Criteria

• 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
• Unable to refrain from taking any non-metformin anti-diabetic medication including insulin within ≥ 3 months prior to the study treatment
• Serum calcitonin > 20 ng/L
• Clinically relevant acute or chronic medical conditions or diseases of the cardiovascular, gastrointestinal, hepatic, renal, endocrine, pulmonary, neurologic, psychiatric, immune or dermatologic systems
• Diagnosis of T1DM or secondary forms of diabetes
• Individual or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia 2 (MEN2), or suspected MTC
• History of pancreatitis
• 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: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
SAD Cohorts 1 to 2: Participants receiving Placebo	Placebo	Participants in each SAD cohort will be randomized to receive placebo.
MAD Cohorts 1 to 4: Participants receiving Placebo	Placebo	Participants will be randomized to receive a once-daily dose of placebo for 28 days.
SAD Cohorts 1 to 2: Participants receiving ECC5004	ECC5004	Participants in each SAD cohort will be randomized to receive up to 4 escalating doses of ECC5004 ranging from 1 mg to 300 mg.
MAD Cohorts 1 to 4: Participants receiving ECC5004	ECC5004	Participants will be randomized to receive a once-daily dose of 1 of 4 escalating doses of ECC5004 ranging from 10 mg to 150 mg for 28 days.

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 Day 8 and MAD: Up to Day 35	Safety Assessment evaluated through adverse events, laboratory evaluations, vital signs, ECGs, and physical examination.

Secondary Outcome Measures

Name	Time	Method
Pharmacodynamic Parameters: AUC0-4 for C-peptide	MAD: Up to Day 30	AUC from time 0 to 4 hour dosing interval
Pharmacodynamic Parameters: Fasting plasma glucose	MAD: Up to Day 30	Change from baseline
Pharmacodynamic Parameters: Fasting plasma glucose homeostatic model assessment	MAD: Up to Day 30	Fasting plasma glucose homeostatic model assessment
Pharmacokinetic Parameters: AUC0-infinity	SAD: Up to Day 3	AUC from time 0 extrapolated to infinity
Pharmacokinetic Parameters: tmax	SAD: Up to Day 3 and MAD: Up to Day 30	Time of the maximum observed plasma concentration
Pharmacodynamic Parameters: Fasting plasma insulin homeostatic model assessment	MAD: Up to Day 30	Fasting plasma insulin homeostatic model assessment
Pharmacokinetic Parameters: tlast	SAD: Up to Day 3	Time of last measurable non-zero concentration
Pharmacokinetic Parameters: AUC0-tau	MAD: Up to Day 30	AUC over a dosing interval from time 0 to time of last quantifiable concentration
Pharmacokinetic Parameters: C24	SAD: Up to Day 3 and MAD: Up to Day 30	Observed concentration at 24 hours post dose
Pharmacokinetic Parameters: t1/2	SAD: Up to Day 3 and MAD: Up to Day 30	Apparent terminal elimination half-life
Pharmacokinetic Parameters: CL/F	SAD: Up to Day 3 and MAD: Up to Day 30	Apparent Clearance
Pharmacodynamic Parameters: AUC0-4 for insulin	MAD: Up to Day 30	AUC from time 0 to 4 hour dosing interval
Pharmacodynamic Parameters: AUC0-4 for glucagon	MAD: Up to Day 30	AUC from time 0 to 4 hour dosing interval
Pharmacodynamic Parameters: Body Weight and Waist Circumference	MAD: Up to Day 30	Change from baseline
Pharmacokinetic Parameters: AUC0-24	SAD: Up to Day 3 and MAD: Up to Day 30	AUC from time 0 to 24 hour dosing interval
Pharmacokinetic Parameters: AUC0-tlast	SAD: Up to Day 3	AUC from time 0 to the time of last quantifiable non-zero concentration
Pharmacokinetic Parameters: Cmax	SAD: Up to Day 3 and MAD: Up to Day 30	Maximum observed plasma concentration
Pharmacokinetic Parameters: Ctau	MAD: Up to Day 30	Observed concentration at the end of the dosing interval
Pharmacokinetic Parameters: tlag	SAD: Up to Day 3 and MAD: Up to Day 30	Lag time (time delay between dosing and first observed plasma concentration)
Pharmacokinetic Parameters: Clast	SAD: Up to Day 3	Last measurable non-zero concentration
Pharmacodynamic Parameters: AUC0-4 for glucose	MAD: Up to Day 30	AUC from time 0 to 4 hour dosing interval
Pharmacodynamic Parameters: Mean daily glucose	MAD: Up to Day 30	Change from baseline

Trial Locations

Locations (1)

Eccogene Investigational Site; 🇺🇸 Anaheim, California, United States