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

• Sponsor: Dongguan HEC Biopharmaceutical R&D Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT05943886
• Collaborator: (none)
• Enrollment: 164
• Location: 1
• Arms: 15
• Actual Duration (Months): 18.2
• Patients Per Site Per Month: 9

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Healthy Subjects; Obesity; T2DM (Type 2 Diabetes Mellitus)	Drug: HEC88473 injection; Drug: Placebo	Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 164 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Aug 11, 2021
• Actual Primary Completion Date: Feb 17, 2023
• Actual Study Completion Date: Feb 17, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) after a single dose of HEC88473 [Baseline to day 15]

   Adverse Events (AEs)

2. Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) after multiple dose of HEC88473 [Baseline to day 43]

   Adverse Events (AEs)

3. Cmax [Predose and postdose 4、8、10、12、14、24、48、72、96、168、216、336 hours]

   Maximum observed serum concentration of HEC88473

4. AUC [Predose and postdose 4、8、10、12、14、24、48、72、96、168、216、336 hours]

   Area under the serum concentration-time curve (AUC)

Secondary Outcome Measures

1. OGTT [Day-1, Day3 and Day 7]

   Oral glucose tolerance test

2. Change from baseline of Adiponectin at day 38 [Baseline to day 38]

   Adiponectin

3. Fasting lipid concentration [Baseline to day 43]

   Fasting lipid concentration

4. Change from baseline of HbA1c at day 38 [Baseline to day 38]

   HbA1c

5. Assessment of the incidence of anti drug antibodies (ADA) developed against HEC88473 after dosing [Baseline to day 43]

   anti drug antibodies (ADA)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

1. Have serum calcitonin ≥20 ng/L at screening.

2. 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.

3. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The First Hospital of Jilin University	Changchun	Jilin	China	130000

Sponsors and Collaborators

• Dongguan HEC Biopharmaceutical R&D Co., Ltd.

Investigators

• Principal Investigator: Yanhua Ding, Doctor, The First Hospital of Jilin University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dongguan HEC Biopharmaceutical R&D Co., Ltd.
• ClinicalTrials.gov Identifier: NCT05943886
• Other Study ID Numbers: HEC88473-DM-101
• First Posted: Jul 13, 2023
• Last Update Posted: Jul 17, 2023
• Last Verified: Jul 1, 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diabetes Mellitus, Type 2

Study Results

No Results Posted as of Jul 17, 2023