Phase Ia Clinical Study of HDM1005 Injection

Phase 1

Completed

• Conditions: Obesity and Overweight
• Interventions: Drug: HDM1005 injection or placebo

• Registration Number: NCT06640647
• Lead Sponsor: Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd.

Brief Summary

This is a randomized, double-blind, placebo-controlled, single-dose, dose-escalation Phase Ia clinical study. It is aimed to evaluate the safety, tolerability, PK and PD characteristics of HDM1005 injection in healthy adult subjects.

Detailed Description

In this study, 7 dose cohorts will be set up, with 10 subjects in each cohort, and subjects in each cohort will be randomized in a 4:1 ratio to receive HDM1005 injection or placebo via subcutaneous injection. Proposed dose cohorts include: Cohort 1 (0.1 mg), Cohort 2 (0.25 mg), Cohort 3 (0.5 mg), Cohort 4 (1 mg), Cohort 5 (2.5 mg), Cohort 6 (5 mg), and Cohort 7 (10 mg). Scientific review committee (SRC) will be established to review the data in a blinded manner to confirm whether to proceed with the next cohort and determine the dose for the next cohort according to both protocol and data obtained from previous cohorts. Administration of higher dose cohorts will only be allowed when the safety and tolerability of the lower dose cohorts have been established and are acceptable. SRC composes representatives from the Sponsor (including but not limited to medical responsible, statistician, clinical pharmacologist) and investigator(s). External consultant may be invited as SRC member per specific scientific question.

Study Timeline

• Study Start: 2024-03-19
• Study First Submitted: 2024-05-31
• Primary Completion: 2024-08-06
• Study Completion: 2024-09-26
• Status Verified: 2024-10
• Study First Submitted QC: 2024-10-11
• Last Update Submitted: 2024-10-11
• Study First Posted: 2024-10-14
• Last Update Posted: 2024-10-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 65

Inclusion Criteria

1. Chinese subjects aged 18 to 55 (including 18 and 55 years old), male or female subjects
2. BMI at the time of screening was between 19.0 and 32.0 kg/m2 (including 19.0 and 32.0 kg/m2), and the weight of female subjects was ≥45 kg and that of male subjects was ≥50 kg
3. Normal or abnormal vital signs, physical examination, laboratory examination, 12-lead ECG and chest imaging during the screening period have no clinical significance
4. Fertile female subjects, from 14 days before signing the ICF to 2 months after the administration of the drug, have taken and agreed to continue to take effective contraceptive measures, and have no family planning or egg donation plan; Male subjects had no plans to have children, no plans to donate sperm, and agreed to use highly effective contraceptive methods from signing ICF to 4 months after dosing
5. Be able to understand the procedures and methods of this study, voluntarily sign ICF, and be willing to strictly follow the requirements of clinical trial protocol to complete relevant procedures

Exclusion Criteria

1. Previous diagnosis of type 1, type 2, or other types of diabetes

2. History or family history of medullary thyroid carcinoma, thyroid C-cell hyperplasia, or multiple endocrine adenomatosis type 2

3. As determined by the investigator, the subject has a co-existing disease or condition that affects gastric emptying or gastrointestinal nutrient absorption. Or a history of acute pancreatitis or acute gallbladder disease within 3 months prior to signing the ICF

4. Had any malignancy within 5 years prior to signing the ICF (except for basal cell carcinoma that has received curative treatment and is considered cured)

5. Cardiovascular and cerebrovascular diseases, gastrointestinal diseases, diabetes mellitus, medullary thyroid cancer, thyroid C cell hyperplasia, multiple endocrine adenomatosis type 2, chronic pancreatitis, and malignant tumors with obvious clinical significance were present; And any respiratory, neurological, urogenital, hematological, or endocrine disorders that may affect the safety of the subject or the findings of the study

6. Patients who have undergone major surgery within 3 months before signing the ICF, or who plan to undergo surgery during the study period

7. Known allergy to any component of the investigational drug or prior history of severe drug allergy

8. Drugs (including prescription drugs, over-the-counter drugs, Chinese herbs, health products, etc.) that have been used within 3 months before signing the ICF and have been determined by researchers to significantly affect body weight and blood sugar.

9. Participated in any clinical trial within 30 days prior to randomization or within 5 half-lives (whichever is older) after the last administration of the investigational drug in the clinical trial (except those who signed ICF and did not receive drug or device intervention)

10. Any of the auxiliary test indicators during the screening period meet the following criteria:

    1. Alanine aminotransferase >1.5x upper limit of normal (ULN), or ASpartate aminotransferase >1.5x ULN, alkaline phosphatase >1.5x ULN, or total bilirubin >1.5x ULN (subjects with Gilbert's syndrome can participate in this study if direct bilirubin ≤ULN);
    2. calcitonin ≥50 ng/L;
    3. Blood amylase or lipase >ULN;
    4. Thyroid stimulating hormone >6.0 mIU/L or <0.4 mIU/L;
    5. Hemoglobin a1C (HbA1c) ≥6.0%; Fasting blood glucose ≥6.1 mmol/L or < 3.9 mmol/L; Or OGTT 2 h blood glucose ≥7.8 mmol/L;
    6. eGFR < 60 mL/min/1.73m2;
    7. Male QTcF>450 ms, female QTcF>470 ms

11. People tested positive for infectious diseases 12 Habitual smokers, alcoholics and drug abusers;

12. Pregnant or lactating women 14. Blood donors within 3 months prior to randomization 15. In the Investigator's opinion, the subject is not suitable to participate in any other circumstances of the trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HDM1005 injection 0.1mg	HDM1005 injection or placebo	HDM1005 injection or placebo 0.1mg once subcutaneous injection
HDM1005 injection 0.25mg	HDM1005 injection or placebo	HDM1005 injection or placebo 0.25mg once subcutaneous injection
HDM1005 injection 0.5mg	HDM1005 injection or placebo	HDM1005 injection or placebo 0.5mg once subcutaneous injection
HDM1005 injection 1.0mg	HDM1005 injection or placebo	HDM1005 injection or placebo 1.0mg once subcutaneous injection
HDM1005 injection 2.5mg	HDM1005 injection or placebo	HDM1005 injection or placebo 2.5mg once subcutaneous injection
HDM1005 injection 5.0mg	HDM1005 injection or placebo	HDM1005 injection or placebo 5.0mg once subcutaneous injection
HDM1005 injection 10.0 mg	HDM1005 injection or placebo	HDM1005 injection or placebo 10.0mg once subcutaneous injection

Primary Outcome Measures

Name	Time	Method
Safety Outcomes	Signing informed until day 29	The incidence, severity, and causality of adverse events (AE) and serious adverse events (SAEs) occurring during treatment, resulting in early termination of TEAEs, resulting in death of TEAEs; etc.

Secondary Outcome Measures

Name	Time	Method
PK Outcomes	0-672 hour(s)	PK parameters include, but are not limited to Area under the plasma concentration versus time curve (AUC)
PD Outcomes	Baseline to day 29	Changes in body weight, body mass index (BMI), fasting glucose, fasting insulin, fasting C-peptide, blood lipids compared to baseline

Trial Locations

Locations (1)

The Second Affiliated Hospital of Anhui Medical University; 🇨🇳 Hefei, China