Paroxysmal nocturnal hemoglobinuria
Conditions
Interventions
SAD stage CMS-D017 group:Six dose groups (50 mg, 100 mg, 200 mg, 400 mg, 800 mg and 1200 mg) were taken orally on an empty stomach.
SAD stage placebo group:Six dose groups (50 mg, 100 mg, 200 mg, 400 mg, 800 mg and 1200 mg) were taken orally on an empty stomach.
MAD stage CMS-D017 group:Four dose groups (50 mg BID, 100 mg BID, 200 mg BID, 400 mg QD) were taken orally on an empty stomach.
MAD stage placebo group:Four dose groups (50 mg BID, 100 mg BID, 200 mg BID, 400 mg QD) were taken orally on an empty stomach.
Sponsors
Peking University Third Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Inclusion criteria
Inclusion criteria: 1. Voluntarily participate in this study and sign the Informed Consent Form; 2. Be able to communicate well with the investigator, understand and comply with all requirements and restrictions of the study, and complete the study according to the protocol; 3. Aged 18–55 years (inclusive, based on the date of signing the Informed Consent Form), male or female; 4. Body Mass Index (BMI) at screening within the range of 19.0–26.0 kg/m² (inclusive), with female body weight >= 45.0 kg and male body weight >= 50.0 kg; 5. Participants of childbearing potential (including their partners) 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. During this period, they must comply with relevant contraception requirements (see Appendix 1) and agree to use at least one highly effective non-hormonal contraceptive method.
Exclusion criteria
Exclusion criteria: Allergy History 1. History of severe allergies, including food allergies, or known hypersensitivity to the investigational drug or its components. Medical History/Conditions 2. Any significant medical history or clinical manifestations of cardiovascular, respiratory, digestive, urogenital, hematological, endocrine and metabolic, rheumatological/immunological, neuropsychiatric, or musculoskeletal diseases requiring medication and/or other treatments (including dietary restrictions and physical therapy), and deemed unsuitable for participation 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, or intestinal resection (except appendectomy). 4. History of meningococcal infection in the participant or a first-degree relative. 5. Active infection or acute illness (e.g., fever, nausea, vomiting, or diarrhea) within 2 weeks before screening. 6. Current or history of tuberculosis (TB) infection, or positive TB test results. Note: If TB test results are indeterminate, a repeat test may be conducted. 7. History of major trauma or surgery within 8 weeks before 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 known to prolong cardiac repolarization) • History of cardiac arrest, syncope, or heart failure; myocardial infarction, angina; valvular heart disease; cardiomyopathy or family history; clinically significant arrhythmias (e.g., sick sinus syndrome, atrioventricular block, Adams-Stokes syndrome, Brugada syndrome or family history, long QT syndrome, atrial flutter, atrial fibrillation, supraventricular tachycardia, ventricular tachycardia). Previous/Concomitant Treatments 9. Participation in any other clinical trial involving drugs or medical devices within 3 months before screening, or planned participation during this study, or within 5 half-lives of the previous investigational drug (whichever is longer). 10. Vaccination within 4 weeks before screening or planned vaccination during the study or within 1 month after the last dose (vaccination against meningococcal or pneumococcal diseases is allowed but must be completed at least 2 weeks before dosing). 11. Use of drugs or substances known to be CYP2C8 or CYP3A inducers or inhibitors, or P-glycoprotein inhibitors within 4 weeks before dosing (see Appendix 2). 12. Use of any prescription or over-the-counter medications (including herbal remedies, vitamins, minerals, and dietary supplements) within 2 weeks or at least 5 half-lives before dosing, whichever is longer. Drug Abuse, Alcohol, Tobacco or Nicotine, Dietary/Exercise Restrictions 13. History of drug abuse within 6 months before screening, or positive results on any drug abuse test. 14. Alcohol consumption exceeding 14 units per week within 3 months before screening (1 unit = 360 mL of beer, 150 mL of wine, or 45 mL of spirits), positive alcohol breath test results, or inability to abstain from alcohol during the study. 15. Smoking more than 5 cigarettes per day on average within 3 months before screening, or inability to stop using any tobacco products during the study. 16. Inability to abstain from consuming grapefruit or grapefruit-related citrus fruits (e.g., pomelo) or their juice
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse Events;Safety laboratory tests;Electrocardiogram;Vital signs;Physical examination;Plasma PK parameters of CMS-D017;Inhibition rate of the complement system alternative pathway (AP); | — |
Countries
China
Contacts
Public ContactHaiyan Li
Peking University Third Hospital
Outcome results
None listed