Overview

This trial is a single-center, randomized, double-blind, placebo-controlled, single ascending dose (SAD) Phase I clinical trial conducted in healthy Chinese adults to evaluate the safety, tolerability and PK profiles of a single subcutaneous administration of ACC085 injection in healthy Chinese adults.

This is a single ascending dose study planned to enroll participants into 5 dose groups \[94.4 mg (periumbilical abdomen), 314.8 mg (periumbilical abdomen), 944.4 mg (periumbilical abdomen), 944.4 mg (lateral thigh), and a pending dose of X mg (periumbilical abdomen), which will be determined based on clinical progress\]. Except for Dose Group 3, which plans to enroll 15 participants with a 4:1 ratio of participants receiving investigational product to placebo, all other dose groups will enroll 8 participants each with a 3:1 ratio of participants receiving investigational product to placebo. After all participants in Dose Group 1 complete the 4-week safety and tolerability assessment, if the dose-escalation stopping criteria have not been met, ACC085 will be escalated sequentially to Dose Groups 2-5 (314.8-944.4 mg and pending Dose Group X mg) with reference to the Fibonacci method and PK findings. Participant follow-up will continue until 48 weeks after dosing.

Eligibility

Inclusion Criteria:

1. Voluntarily sign the informed consent form and be able to comply with the requirements of the study procedures;
2. Aged 18 to 55 years at the time of signing the informed consent form (≥18 and \<56 years), male or female;
3. At screening, male body weight ≥50.0 kg, female body weight ≥45.0 kg; body mass index (BMI) = weight (kg)/height² (m²) within the range of 18.5-27.0 kg/m² (inclusive);
4. At screening and within 3 months prior to screening, assessed by the investigator to have no risk of HIV infection (HIV high-risk populations include, but are not limited to, men who have sex with men, intravenous drug users, sex workers, individuals who have unprotected sex with sex workers, individuals with multiple sexual partners, or individuals with concurrent sexually transmitted infections \[STIs\]);
5. Female participants of childbearing potential (WOCBP) and male participants have no plans to conceive (including sperm or oocyte donation) from 1 month prior to informed consent to 1 year after dosing, and agree to use effective contraception (including one or more non-pharmacological contraceptive measures, or no heterosexual intercourse in daily life);
6. No history of serious medical or surgical diseases prior to screening; vital signs, physical examination, 12-lead electrocardiogram (ECG), laboratory tests (complete blood count, serum biochemistry, coagulation function, urinalysis, infectious disease screening, pregnancy test for females, urine drug abuse screening), chest X-ray and breath alcohol test results at screening are normal, or slightly outside the normal reference range but judged by the investigator to be clinically insignificant.

Exclusion Criteria:

1. The investigator judges that the participant has poor treatment compliance or study procedure adherence, or has any other condition unsuitable for participation in this study, or participation in this study cannot maximally protect the participant's health rights and interests; (Population Restrictions)
2. History of drug or other substance abuse within 5 years prior to screening;
3. Female participants who are pregnant or lactating at screening; (Medical History Restrictions)
4. Presence or ongoing clinically significant chronic diseases prior to or at screening, including but not limited to diseases of the cardiovascular and cerebrovascular system, respiratory system, digestive system (any history of gastrointestinal diseases affecting drug absorption), urinary system, hematologic and lymphatic system, endocrine system, musculoskeletal system, immune system, and neuropsychiatric system;
5. Occurrence or ongoing clinically significant acute diseases within 1 month prior to screening or at screening, such as respiratory tract infection requiring antibiotic treatment;
6. Prior to or at screening, known or suspected hypersensitivity to the investigational drug, placebo, or any of their excipients as assessed by the investigator; or history of allergic diathesis (multiple drug and food allergies), or history of allergic diseases (e.g., asthma, urticaria, eczematous dermatitis, etc.);
7. Surgery that may affect drug absorption, distribution, metabolism and excretion within 6 months prior to screening or at screening, or plan to undergo major surgery during the study;
8. Unable to tolerate venipuncture prior to or at screening, or history of needle phobia or hematophobia; blood donation including apheresis blood donation or significant blood loss (≥400 mL), or blood transfusion received within 3 months prior to screening or at screening; or plan to donate blood or receive blood transfusion during the study;
9. 12-lead ECG exceeding the criteria: QTcF \>450 ms for males, QTcF \>470 ms for females; or ECG abnormalities judged clinically significant by the investigator (e.g., atrioventricular block, torsades de pointes (TdP), other types of ventricular tachycardia, ventricular fibrillation and ventricular flutter, clinically significant T-wave changes, or any abnormal 12-lead ECG findings affecting QTc interval); (Lifestyle Restrictions)
10. Average daily consumption greater than 10 cigarettes or equivalent tobacco products within 3 months prior to screening or at screening, or inability to stop using any tobacco products during the inpatient study period;
11. Average weekly alcohol consumption greater than 14 units within 3 months prior to screening or at screening (1 unit of alcohol ≈360 mL beer or 45 mL of 40% strength spirits or 150 mL wine), or inability to refrain from any alcohol-containing products during the inpatient study period;
12. Excessive daily consumption of tea, coffee and/or caffeine-containing beverages (average \>8 cups, 1 cup ≈250 mL) within 3 months prior to screening or at screening, or inability to stop drinking tea, coffee and/or caffeine-containing beverages during the inpatient study period;
13. Inability to refrain from consuming pitaya, mango, pomelo, carambola, or foods/beverages prepared from them, or foods/beverages containing xanthine, caffeine or alcohol (including chocolate, tea, coffee, cola, cocoa, etc.), or other special diets affecting drug absorption, distribution, metabolism and excretion within 48 h prior to study drug administration;
14. Special dietary requirements, or inability to accept standardized meals;
15. Tattoos or other skin conditions at the injection site assessed by the investigator as potentially interfering with the assessment of injection site reactions; (Medication History Restrictions)
16. Use of strong CYP3A4 inducers (e.g., rifampicin, efavirenz, carbamazepine, phenobarbital, phenytoin, pioglitazone, St. John's Wort, glucocorticoids, etc.) or strong/moderate CYP3A inhibitors (e.g., voriconazole, clarithromycin, telithromycin, ketoconazole, itraconazole, nefazodone, etc.) within 28 days prior to screening or 5 drug half-lives, whichever is longer;
17. Use of strong or moderate UGT1A inhibitors (e.g., silybin, ritonavir, atazanavir, quinidine, diclofenac, mycophenolic acid, osimertinib, etc.) or strong UGT1A1 inducers (e.g., rifampicin, carbamazepine, phenobarbital, phenytoin, etc.) within 28 days prior to screening or 5 drug half-lives, whichever is longer;
18. Use of P-gp inhibitors (e.g., ranolazine, verapamil, itraconazole, clarithromycin, quinidine, ritonavir) or P-gp substrates (e.g., dabigatran, fexofenadine, digoxin) within 28 days prior to screening or 5 drug half-lives, whichever is longer;
19. Use of any prescription drugs, over-the-counter drugs or Chinese herbal medicines within 14 days prior to screening or 5 drug half-lives, whichever is longer;
20. Participation in any interventional clinical trial including drugs, vaccines or devices within 3 months prior to screening.