The Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of HEC88473 in Healthy Subjects

Phase 1

Completed

• Conditions: Non-alcoholic Steatohepatitis
• Interventions: Drug: HEC88473 injection; Drug: Placebo

• Registration Number: NCT04829123
• Lead Sponsor: Dongguan HEC Biopharmaceutical R&D Co., Ltd.

Brief Summary

A Phase 1, double blind, placebo controlled, single and multiple ascending dose, safety, tolerability, pharmacokinetic, and pharmacodynamic study of HEC88473 in healthy subjects

Detailed Description

This is the first time HEC88473 will be administered to humans. The aim of this study is to obtain safety, tolerability, PK, PD, and immunogenicity data of HEC88473 SC administration as single and multiple ascending doses in healthy subjects.

Study Timeline

• Study First Submitted: 2021-03-25
• Study First Submitted QC: 2021-04-01
• Study First Posted: 2021-04-02
• Study Start: 2021-05-14
• Primary Completion: 2022-03-02
• Study Completion: 2022-03-02
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-14
• Last Update Posted: 2023-02-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

1. Males or females, of any race, between 18 and 60 years of age, inclusive, at screening.
2. Body weight ≥ 50 kg, and body mass index between 18.0 and 40.0 kg/m2, inclusive, at screening.
3. In good health, determined by no clinically significant findings from medical history, physical examination, 12 lead ECG, vital signs measurements, and clinical laboratory evaluations at screening as assessed by the investigator (or designee).
4. Able to comprehend and willing to sign an ICF and to abide by the study restrictions.

Exclusion Criteria

1. Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator (or designee).
2. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator (or designee).
3. History of alcoholism or drug/chemical abuse within 2 years prior to the first dosing.
4. Alcohol consumption of > 21 units per week for males and > 14 units per week for females. One unit of alcohol equals 12 oz (360 mL) beer, 1½ oz (45 mL) liquor, or 5 oz (150 mL) wine.
5. Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) at screening and/or check-in.
6. Immunization with a live attenuated vaccine or coronavirus vaccination within 1 month prior to the first dosing or planned vaccination during the course of the study.
7. Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days or 5 half-lives (if known), whichever is longer, prior to the first dosing.
8. Use or intend to use any prescription medications/products other than hormone replacement therapy, oral, implantable, transdermal, injectable, or intrauterine contraceptives within 14 days prior to first dosing, unless deemed acceptable by the investigator (or designee).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Single dose of 0.5 mg HEC88473	Placebo	Healthy subjects, receiving a single dose of 0.5 mg HEC88473 (N=6) or placebo(N=2) after meal.
Single dose of 0.5 mg HEC88473	HEC88473 injection	Healthy subjects, receiving a single dose of 0.5 mg HEC88473 (N=6) or placebo(N=2) after meal.
Single dose of 1.7 mg HEC88473	Placebo	Healthy subjects, receiving a single dose of 1.7 mg HEC88473 (N=6) or placebo(N=2) after meal.
Single dose of 1.7 mg HEC88473	HEC88473 injection	Healthy subjects, receiving a single dose of 1.7 mg HEC88473 (N=6) or placebo(N=2) after meal.
Single dose of 5.1 mg HEC88473	Placebo	Healthy subjects, receiving a single dose of 5.1 mg HEC88473 (N=6) or placebo(N=2) after meal.
Single dose of 10.2 mg HEC88473	HEC88473 injection	Healthy subjects, receiving a single dose of 10.2 mg HEC88473 (N=6) or placebo(N=2) after meal.
Single dose of 17.0 mg HEC88473	HEC88473 injection	Healthy subjects, receiving a single dose of 17.0 mg HEC88473 (N=6) or placebo(N=2) after meal.
Single dose of 17.0 mg HEC88473	Placebo	Healthy subjects, receiving a single dose of 17.0 mg HEC88473 (N=6) or placebo(N=2) after meal.
Single dose of 5.1 mg HEC88473	HEC88473 injection	Healthy subjects, receiving a single dose of 5.1 mg HEC88473 (N=6) or placebo(N=2) after meal.
Single dose of 34.0 mg HEC88473	HEC88473 injection	Healthy subjects, receiving a single dose of 34.0 mg HEC88473 (N=6) or placebo(N=2) after meal.
Multiple doses of 1.7 mg HEC88473	Placebo	Healthy subjects, receiving a weekly dose of 1.7 mg HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal.
Multiple doses of 10.2 mg HEC88473	Placebo	Healthy subjects, receiving a weekly dose of 10.2 mg HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal.
Single dose of 44.2 mg HEC88473	Placebo	Healthy subjects, receiving a single dose of 44.2 mg HEC88473 (N=6) or placebo(N=2) after meal.
Single dose of 10.2 mg HEC88473	Placebo	Healthy subjects, receiving a single dose of 10.2 mg HEC88473 (N=6) or placebo(N=2) after meal.
Single dose of 25.5 mg HEC88473	HEC88473 injection	Healthy subjects, receiving a single dose of 25.5 mg HEC88473 (N=6) or placebo(N=2) after meal.
Single dose of 34.0 mg HEC88473	Placebo	Healthy subjects, receiving a single dose of 34.0 mg HEC88473 (N=6) or placebo(N=2) after meal.
Single dose of 25.5 mg HEC88473	Placebo	Healthy subjects, receiving a single dose of 25.5 mg HEC88473 (N=6) or placebo(N=2) after meal.
Single dose of 44.2 mg HEC88473	HEC88473 injection	Healthy subjects, receiving a single dose of 44.2 mg HEC88473 (N=6) or placebo(N=2) after meal.
Multiple doses of 5.1 mg HEC88473	Placebo	Healthy subjects, receiving a weekly dose of 5.1 mg HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal.
Multiple doses of 1.7 mg HEC88473	HEC88473 injection	Healthy subjects, receiving a weekly dose of 1.7 mg HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal.
Multiple doses of 5.1 mg HEC88473	HEC88473 injection	Healthy subjects, receiving a weekly dose of 5.1 mg HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal.
Multiple doses of 10.2 mg HEC88473	HEC88473 injection	Healthy subjects, receiving a weekly dose of 10.2 mg HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal.

Primary Outcome Measures

Name	Time	Method
Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) after a single dose of HEC88473	Baseline to day 15
Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) after multiple dose of HEC88473	Baseline to day 43
AUC	Predose and postdose 4, 8, 10, 12, 14, 24, 48, 72, 96, 168, 216, and 336 hours	Area under the plasma concentration-time curve (AUC)
Cmax	Predose and postdose 4, 8, 10, 12, 14, 24, 48, 72, 96, 168, 216, and 336 hours	Maximum observed plasma concentration of HEC88473

Secondary Outcome Measures

Name	Time	Method
OGTT	Predose and postdose 2, 4 hours	Oral glucose tolerance test
Assessment of the incidence of anti drug antibodies (ADA) developed against HEC88473 after dosing	Baseline to day 43

Trial Locations

Locations (1)

Scientia Clinical Research; 🇦🇺 Sydney, Australia