A Phase 1 Study of HEC88473 Injection in Healthy Subjects, Obese Subjects and T2DM Subjects

A Phase 1, Randomised, Double-blind, Placebo-controlled, Single and Multiple Dose Study to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HEC88473 Injection in Healthy Subjects, Obese Subjects and T2DM Subjects

This is a single-center, randomized, double-blind, placebo-controlled, escalating single-dose and multiple-dose study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of HEC88473 injection in healthy subjects, obese subjects and subjects with type 2 diabetes mellitus (T2DM).

Study Overview

• Status: Completed
• Conditions: Obesity; Healthy Subjects; T2DM (Type 2 Diabetes Mellitus)
• Intervention / Treatment: Drug: HEC88473 injection; Drug: Placebo

Detailed Description

This study is divided into two parts, Part A is an escalating single-dose study in healthy subjects and obese subjects, and Part B is an escalating multiple-dose study in subjects with T2DM.

• Study Type: Interventional
• Enrollment (Actual): 164
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China, 130000
      • The First Hospital of Jilin University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Part A

1. Males or females, between 18 and 45 years of age, inclusive, at screening.
2. Body weight ≥ 50 kg for males and body weight ≥ 45 kg for females. 18≤body mass index (BMI)<28 kg/m2 for nonobese subjects and 28≤BMI≤45 kg/m2 for obese subjects.

Part B

1. Males or females, between 18 and 65 years of age, inclusive, at screening.
2. 24 kg/m2≤BMI≤35 kg/m2.
3. Subjects diagnosed with T2DM, newly diagnosed subjects at screening, or treated with diet and exercise alone within 3 months before screening and still have poor blood glucose control, or treated with a stable dose of metformin for ≥ 3 months before screening.
4. 7.0%≤ HbA1c ≤10.5% at screening.

Exclusion Criteria:

Part A

1. Smoked more than 5 cigarettes per day within 3 months before the study.
2. Immunization with a live attenuated vaccine or coronavirus vaccination within 1 month prior to screening or planned vaccination during the course of the study.
3. Positive alcohol breath test result or positive urine drug screen.
4. Blood donation (> 300 mL) or massive blood loss (> 400 mL) within 3 months before screening.

Part B

1. Have type 1 diabetes mellitus.
2. Have had ≥1 episode of severe hypoglycemia within 6 months before screening, or history of recurrent hypoglycemia (history of hypoglycemia more than 3 times in 3 months).
3. Have acute or chronic hepatitis, signs and symptoms of any other liver disease other than nonalcoholic fatty liver disease (NAFLD), or alanine aminotransferase (ALT) level >5 times the upper limit of the reference range at screening.
4. Have serum calcitonin ≥20 ng/L at screening.
5. Have a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2; or have hereditary diseases that can easily induce MTC.
6. Fasted triglycerides > 5.7 mmol/L at screening. If the patient is on lipid-lowering therapies, doses must be stable for 30 days prior to screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

15

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single dose of 0.5 mg HEC88473; Healthy subjects, receiving a single dose of 0.5 mg HEC88473 (N=8) or placebo(N=2) after meal.	Drug: HEC88473 injection; HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen.; Drug: Placebo; Placebo will be administered by subcutaneous injection in the abdomen.
Experimental: Single dose of 1.7 mg HEC88473; Healthy subjects, receiving a single dose of 1.7 mg HEC88473 (N=8) or placebo(N=2) after meal.	Drug: HEC88473 injection; HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen.; Drug: Placebo; Placebo will be administered by subcutaneous injection in the abdomen.
Experimental: Single dose of 5.1 mg HEC88473; Healthy subjects, receiving a single dose of 5.1 mg HEC88473 (N=8) or placebo(N=2) after meal. Obese subjects, receiving a single dose of 5.1 mg HEC88473 (N=8) or placebo(N=2) after meal.	Drug: HEC88473 injection; HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen.; Drug: Placebo; Placebo will be administered by subcutaneous injection in the abdomen.
Experimental: Single dose of 10.2 mg HEC88473; Healthy subjects, receiving a single dose of 10.2 mg HEC88473 (N=8) or placebo(N=2) after meal.	Drug: HEC88473 injection; HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen.; Drug: Placebo; Placebo will be administered by subcutaneous injection in the abdomen.
Experimental: Single dose of 17.0 mg HEC88473; Healthy subjects, receiving a single dose of 17.0 mg HEC88473 (N=8) or placebo(N=2) after meal.	Drug: HEC88473 injection; HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen.; Drug: Placebo; Placebo will be administered by subcutaneous injection in the abdomen.
Experimental: Single dose of 25.5 mg HEC88473; Healthy subjects, receiving a single dose of 25.5 mg HEC88473 (N=8) or placebo(N=2) after meal.	Drug: HEC88473 injection; HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen.; Drug: Placebo; Placebo will be administered by subcutaneous injection in the abdomen.
Experimental: Single dose of 35.7 mg HEC88473; Healthy subjects, receiving a single dose of 35.7 mg HEC88473 (N=8) or placebo(N=2) after meal.	Drug: HEC88473 injection; HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen.; Drug: Placebo; Placebo will be administered by subcutaneous injection in the abdomen.
Experimental: Single dose of 47.6 mg HEC88473; Healthy subjects, receiving a single dose of 47.6 mg HEC88473 (N=8) or placebo(N=2) after meal.	Drug: HEC88473 injection; HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen.; Drug: Placebo; Placebo will be administered by subcutaneous injection in the abdomen.
Experimental: Single dose of 62.9 mg HEC88473; Healthy subjects, receiving a single dose of 62.9 mg HEC88473 (N=8) or placebo(N=2) after meal.	Drug: HEC88473 injection; HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen.; Drug: Placebo; Placebo will be administered by subcutaneous injection in the abdomen.
Experimental: Single dose of 81.6 mg HEC88473; Healthy subjects, receiving a single dose of 81.6 mg HEC88473 (N=8) or placebo(N=2) after meal.	Drug: HEC88473 injection; HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen.; Drug: Placebo; Placebo will be administered by subcutaneous injection in the abdomen.
Experimental: Multiple doses of 5.1 mg HEC88473; T2DM subjects, receiving a weekly dose of 5.1 mg HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal.	Drug: HEC88473 injection; HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen.; Drug: Placebo; Placebo will be administered by subcutaneous injection in the abdomen.
Experimental: Multiple doses of 15.3 mg HEC88473; T2DM subjects, receiving a weekly dose of 15.3 mg HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal.	Drug: HEC88473 injection; HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen.; Drug: Placebo; Placebo will be administered by subcutaneous injection in the abdomen.
Experimental: Multiple doses of 30.6 mg HEC88473; T2DM subjects, receiving a weekly dose of HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal. The 30.6 mg cohort was administered by titration.	Drug: HEC88473 injection; HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen.; Drug: Placebo; Placebo will be administered by subcutaneous injection in the abdomen.
Experimental: Multiple doses of 45.9 mg HEC88473; T2DM subjects, receiving a weekly dose of HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal. The 45.9 mg cohort was administered by titration.	Drug: HEC88473 injection; HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen.; Drug: Placebo; Placebo will be administered by subcutaneous injection in the abdomen.
Experimental: Multiple doses of 68.0 mg HEC88473; T2DM subjects, receiving a weekly dose of HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal. The 68.0 mg cohort was administered by titration.	Drug: HEC88473 injection; HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen.; Drug: Placebo; Placebo will be administered by subcutaneous injection in the abdomen.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OGTT	Oral glucose tolerance test	Day-1, Day3 and Day 7
Fasting lipid concentration	Fasting lipid concentration	Baseline to day 43
Assessment of the incidence of anti drug antibodies (ADA) developed against HEC88473 after dosing	anti drug antibodies (ADA)	Baseline to day 43
Change from baseline of Adiponectin at day 38	Adiponectin	Baseline to day 38
Change from baseline of HbA1c at day 38	HbA1c	Baseline to day 38

Collaborators and Investigators

• Sponsor: Dongguan HEC Biopharmaceutical R&D Co., Ltd.
• Investigators: Principal Investigator: Yanhua Ding, Doctor, The First Hospital of Jilin University

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2021
• Primary Completion (Actual): February 17, 2023
• Study Completion (Actual): February 17, 2023

Study Registration Dates

• First Submitted: July 5, 2023
• First Submitted That Met QC Criteria: July 5, 2023
• First Posted (Actual): July 13, 2023

Study Record Updates

• Last Update Posted (Actual): July 17, 2023
• Last Update Submitted That Met QC Criteria: July 14, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: HEC88473-DM-101

Drug and device information, study documents

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