Clinical trial NCT05943886: A Phase 1 Study of HEC88473 Injection in Healthy Subjects, Obese Subjects and T2DM Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Obesity
T2DM (Type 2 Diabetes Mellitus)
Lead sponsor: Dongguan HEC Biopharmaceutical R&D Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-07-13
Enrollment: 164
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) after a single dose of HEC88473
timeFrame: Baseline to day 15
measure: Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) after multiple dose of HEC88473
timeFrame: Baseline to day 43
measure: Cmax
timeFrame: Predose and postdose 4、8、10、12、14、24、48、72、96、168、216、336 hours
measure: AUC
timeFrame: Predose and postdose 4、8、10、12、14、24、48、72、96、168、216、336 hours
Secondary outcomes:
measure: OGTT
timeFrame: Day-1, Day3 and Day 7
measure: Change from baseline of Adiponectin at day 38
timeFrame: Baseline to day 38
measure: Fasting lipid concentration
timeFrame: Baseline to day 43
measure: Change from baseline of HbA1c at day 38
timeFrame: Baseline to day 38
measure: Assessment of the incidence of anti drug antibodies (ADA) developed against HEC88473 after dosing
timeFrame: Baseline to day 43
Other outcomes:
Locations:
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
Study officials:
affiliation: The First Hospital of Jilin University
name: Yanhua Ding, Doctor
role: PRINCIPAL_INVESTIGATOR
References: