A Phase I Clinical Trial to Evaluate CMS-D017 Following Single and Multiple Doses in Healthy Participants

A Randomized, Double-blind, Placebo-controlled, Dose-escalation Phase I Study to Evaluate the Safety, Tolerability, PK and PD Characteristics of CMS-D017 Following Single and Multiple Administrations in Healthy Participants

This study is a first-in-human (FIH) trial of CMS-D017 conducted in healthy Chinese adult participants, consisting of two parts: Part 1-a single ascending dose (SAD) study (referred to as Part 1 SAD), and Part 2-a multiple ascending dose (MAD) study (referred to as Part 2 MAD). The study aims to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) characteristics of CMS-D017 capsules following single and multiple oral administrations in healthy Chinese adult participants.

Both parts of the study are designed as randomized, double-blind, placebo-controlled, sequential cohort trials. Part 1 SAD plans to include 6 dose cohorts, with 8 participants per cohort (6 receiving CMS-D017 and 2 receiving placebo), for a total of 48 participants. Part 2 MAD plans to include 4 dose cohorts, with 10 participants per cohort (8 receiving CMS-D017 and 2 receiving placebo), for a total of 40 participants.

Inclusion Criteria:

1. Voluntarily participates in this study and signs the informed consent form.
2. Able to communicate well with the investigator and understands and complies with all requirements and restrictions of this study, and is able to complete the study in accordance with the protocol.
3. Aged 18-55 years (inclusive, as of the day of signing the informed consent form), male or female.
4. Body Mass Index (BMI) between 19.0 and 26.0 kg/m² (inclusive) at screening, with females weighing ≥ 45.0 kg and males weighing ≥ 50.0 kg.
5. Participants (and their partners) with reproductive capacity must have no plans for pregnancy, egg donation, or sperm donation from the date of signing the informed consent form until 3 months after the last dose of the study drug, and must comply with contraceptive requirements (see Appendix 1), agreeing to use at least one highly effective non-hormonal contraceptive method.

Exclusion Criteria:

Allergy History

1. History of severe allergies, including food allergies, or allergy to the study drug or its components.

   Medical History/Conditions

2. Significant history or clinical manifestations of cardiovascular, respiratory, digestive, urogenital, hematologic, endocrine and metabolic, rheumatic, immunologic, neuropsychiatric, or musculoskeletal diseases requiring medication and/or other treatments (including dietary restrictions and physical therapy), as deemed unsuitable for participation in this study by the investigator.

3. Any condition that may affect drug absorption, including but not limited to: malabsorption syndrome, inflammatory bowel disease, celiac disease, gastrectomy, cholecystectomy, bowel resection (except appendectomy).

4. History of meningococcal infection or first-degree relatives with history of meningococcal infection.

5. Active infection or acute disease state (e.g., fever, nausea, vomiting, or diarrhea) within 2 weeks prior to screening.

6. Current history of tuberculosis infection; or positive tuberculosis (TB) test result. Note: If the TB test result is indeterminate, one repeat test is allowed.

7. History of severe trauma or surgery within 8 weeks prior to screening, or planned surgery during the study period.

8. History or current presence of the following cardiac risk factors:

   Torsades de pointes or risk factors (e.g., hypokalemia, hypomagnesemia, use of drugs causing delayed cardiac repolarization) History of cardiac arrest, syncope, heart failure; myocardial infarction, angina; valvular heart disease; cardiomyopathy or family history; clinically significant arrhythmias (e.g., sick sinus syndrome, atrioventricular conduction block, Adams-Stokes syndrome, Brugada syndrome or family history, long QT syndrome, atrial flutter, atrial fibrillation, supraventricular tachycardia, ventricular tachycardia).

   Prior/Concomitant Treatments

9. Participation in any other clinical study involving drugs or medical devices within 3 months prior to screening, or planned participation in such studies during this study, or within 5 half-lives of that drug (whichever is longer).

10. Vaccination within 4 weeks prior to screening or planned vaccination during the study or within 1 month after last dose (participants vaccinated against meningococcal and pneumococcal infections may be included if vaccination was completed at least 2 weeks before dosing).

11. Use of known CYP2C8 or CYP3A inducers or inhibitors, or P-gp inhibitors within 4 weeks prior to dosing (see Appendix 2).

12. Use of any prescription or over-the-counter drugs (including herbal medicines, vitamins, minerals, and dietary supplements) within 2 weeks or at least 5 half-lives prior to dosing, whichever is longer.

    Substance Use, Alcohol, Tobacco, or Nicotine, Dietary/Exercise Restrictions

13. History of drug abuse within 6 months prior to screening, or positive result for any drug abuse test.

14. Alcohol consumption exceeding 14 units per week within 3 months prior to screening (1 unit = 360 mL beer, 150 mL wine, or 45 mL spirits), or positive breath alcohol test, or inability to abstain from alcohol during the study.

15. Average smoking of more than 5 cigarettes per day within 3 months prior to screening, or inability to stop using any tobacco products during the study.

16. Inability to abstain from grapefruit or grapefruit-related citrus fruits or juices (e.g., pomelo) within 7 days prior to dosing and during the study.

17. Consumption of caffeine-containing products (e.g., coffee, tea, cola, other caffeinated beverages, or chocolate) within 3 days prior to dosing, or refusal to avoid such products throughout the study.

18. Engagement in strenuous exercise or physical activity within 3 days prior to dosing, or refusal to avoid such activities throughout the study.

    Examinations and Assessments

19. Corrected QT interval (using Fridericia's formula, QTcF = QT/(RR^0.33)) > 450 msec in males or females.

20. Abnormal findings in physical examination, vital signs, safety laboratory tests, 12-lead ECG, or other auxiliary tests (chest X-ray, abdominal ultrasound) deemed clinically significant by the investigator.

21. Positive test results for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCVAb), syphilis antibody (TPAb), or human immunodeficiency virus antibody (HIV Ab).

    Other

22. Pregnant or lactating females.

23. Special dietary requirements or inability to comply with standardized diet.

24. Difficulty with venous blood sampling (e.g., history of needle or blood phobia), or poor venous condition as deemed unsuitable for enrollment by the investigator.

25. Donation or loss of ≥ 400 mL blood within 3 months prior to screening, or receipt of blood transfusion or blood products; or planned blood or blood component donation during the study.

26. Other conditions deemed unsuitable for participation in this study by the investigator.