Evaluate the Safety and Tolerability, Healthy and Overweight or Obese Participants
Conditions
Keywords
Phase 1 clinical study, safety, fat loss
Brief summary
This study is a first-in-human clinical trial of CMS-D008 conducted in Chinese healthy and overweight or obese adult participants, consisting of three parts: Part-1 Single Ascending Dose (SAD) study (hereinafter referred to as Part-1 SAD study), Part-2 Multiple Ascending Dose (MAD) study (hereinafter referred to as Part-2 MAD study), and Part-3 expansion study. The study aims to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) characteristics, and immunogenicity of single and multiple subcutaneous injections of CMS-D008 injection in Chinese healthy and overweight or obese adult participants.
Interventions
BIOLOGICALCMS-D008
Healthy and overweight or obese participants
DRUGPlacebo
Healthy and overweight or obese participants
Sponsors
Shenzhen Kangzhe Biotechnology Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Voluntarily participate in this study, sign the informed consent form, be able to understand and comply with all requirements and restrictions of the study, and complete the study in accordance with the protocol. 2. Male or female aged 18-56 years (inclusive) 3. Body mass index (BMI) ≥23 kg/m2 at screening, with stable body weight in the past 4 months 4. Glycated hemoglobin (HbA1c) \< 6.5% and fasting plasma glucose \< 7 mmol/L at screening. 5. Participants of childbearing potential (including their partners) have no plan to conceive, donate oocytes, or donate sperm from the date of signing the informed consent form until 7 months after the last study drug administration, and must comply with contraceptive requirements during this period
Exclusion criteria
1. History or presence of liver disease (except fatty liver disease), allergy, cardiovascular, endocrine (except primary obesity), neuropsychiatric, digestive, respiratory, hematological, immune, or genitourinary system major diseases. 2. History or presence of endocrine diseases that may significantly affect body weight, or obesity caused by medication use, single gene mutation, or genetic obesity syndromes. 3. Any skin conditions that may interfere with the assessment of injection-site reactions. 4. Use of any siRNA agent in the prior 12 months 5. Use of glucagon-like peptide-1 (GLP-1) receptor agonists and other weight-loss medications in the past 6 months. 6. Use of any prescription or non-prescription drugs (including Chinese herbal medicines, vitamins, minerals, and dietary supplements, etc.) within 2 weeks before dosing or at least 5 elimination half-lives, whichever is longer. 7. Participants with clinically significant abnormalities in vital signs, physical examination, laboratory tests, 12-lead ECG, and other auxiliary examinations at screening or baseline, who are considered by the investigator to be ineligible for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline to each visit point in vital signs (temperature, blood pressure, heart rate, respiratory rate) | through study completion,an average of 0.6 years | Measured using electronic sphygmomanometer/thermometer according to standard procedures, record actual values at each visit point, and assess abnormal values. |
| Incidence rate of abnormal findings in comprehensive systemic physical examination | through study completion,an average of 0.6 years | Record abnormal physical examination findings by system (cardiovascular, respiratory, digestive, etc.), summarize the number and incidence rate of abnormalities in each system, and categorize them as related or unrelated to the study drug. |
| Hematology, biochemistry, and urinalysis laboratory test indicators | through study completion,an average of 0.6 years | The tests include complete blood count (WBC, RBC, Hb, etc.), blood biochemistry (ALT, AST, Cr, etc.), and urinalysis; changes from baseline were calculated, and the incidence of abnormal values was summarized according to CTCAE 6.0 grading. |
| 12-lead electrocardiogram QTc interval, heart rate, and incidence of morphological abnormalities | through study completion,an average of 0.6 years | Collected using standard 12-lead ECG equipment, interpreted by a central laboratory, with the number and incidence rate of QTc interval changes, heart rate abnormalities, and morphological abnormalities (such as premature beats, ST-T changes) summarized. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum plasma drug concentration (Cmax) | Through 48 hours post-dose | Calculate the maximum observed plasma concentration from the plasma drug concentration-time curve after administration using non-compartmental analysis (NCA), unit: ng/mL |
| Tmax | Through 48 hours post-dose | Using non-compartmental analysis (NCA) to calculate the time to reach Cmax after drug administration, unit: h |
| Area under the curve (AUC0-t) | Through 48 hours post-dose | Calculate the area under the concentration-time curve from time of administration (0 h) to the last quantifiable concentration time point (t) using non-compartmental analysis (NCA), unit: ng·h/mL |
Outcome results
None listed