A Study to Evaluate the PK Similarity of AK104 in Healthy Chinese Male Participations

Официальное название

A Phase I Study to Evaluate the PK Similarity of AK104 (Anti-PD-1/CTLA-4 Bispecific Antibody) From the Proposed New Manufacturing Site and the Approved Original Site in Chinese Healthy Male Participants.

Обзор

This study is to evaluate the pharmacokinetic (PK) similarity of AK104 (an anti-PD-1/CTLA-4 bispecific antibody) from the proposed new manufacturing site and the approved original site in healthy male participants.

Вмешательства

• Препарат AK104 (New Site)
  AK104 (New Site) 0.2mg/kg
• Препарат AK104 (Original Site)
  AK104 (Original Site) 0.2mg/kg

Первичные конечные точки

• Area under the plasma concentration-time curve (AUC0-infinity) [Срок оценки: From pre-dose to day 22]

Вторичные конечные точки (9)

• Area under the plasma concentration-time curve (AUC0-t) [Срок оценки: From pre-dose to day 22]
• Maximum plasma concentration (Cmax) [Срок оценки: From pre-dose to day 22]
• Volume of distribution (V) [Срок оценки: From pre-dose to day 22]
• Clearance (CL) [Срок оценки: From pre-dose to day 22]
• Ratio of AUC0-t/AUC0-infinity [Срок оценки: From pre-dose to day 22]
• Time to maximum concentration (Tmax) [Срок оценки: From pre-dose to day 22]
• Half-life (t1/2) [Срок оценки: From pre-dose to day 22]
• Incidence and severity of adverse events (AEs) [Срок оценки: Up to day 22]
• Number and percentage of subjects with detectable ADA [Срок оценки: From pre-dose to day 22]

Критерии участия

Критерии включения

• Able to provide signed informed consent prior to the trial and fully understand the trial content, procedures, and potential adverse reactions.
• Able to complete the study as required by the trial protocol.
• Males aged 18 to 45 years.
• Body Mass Index (BMI) is 19.0 \~ 26.0 kg/m² and body weight is 55.0 \~ 75.0 kg.
• Non-sterilized male participants must agree to remain completely abstinent or use a barrier contraceptive method (male condom) during the study period and for 6 months after the completion of the investigational drug infusion, and must refrain from sperm donation. Their female partners must agree to use at least one highly effective contraceptive method (e.g., sterilization surgery, contraceptive pills, injectable contraceptive medroxyprogesterone, or subdermal implant) during the study period and for 6 months after the completion of the investigational drug infusion.

Критерии исключения

• Have a history of diseases of the digestive, respiratory, cardiovascular, endocrine, urinary, nervous, or hematologic systems, or metabolic disorders, which, in the investigator's opinion, is still clinically significant at the time of screening.
• Have a history of malignancy (excluding successfully resected cutaneous squamous cell carcinoma, basal cell carcinoma, or localized cervical carcinoma in situ with no evidence of metastasis).
• Have a history of autoimmune disease (including personal or family history of hereditary immunodeficiency).
• Have a history of tuberculosis or clinical manifestations suggestive of tuberculosis (including but not limited to pulmonary tuberculosis, lymph node tuberculosis, tuberculous pleurisy, etc.).
• Have a history of recurrent or chronic infection, or chronic or recurrent infections including but not limited to: chronic renal infection, chronic chest infection (e.g., bronchiectasis), sinusitis, recurrent urinary tract infection, open, draining, or infected skin wounds.
• Have a history of acute infection within 2 weeks prior to randomization, or opportunistic infection within 6 months prior to randomization (e.g., herpes zoster, active cytomegalovirus, Pneumocystis jirovecii, Histoplasma, Aspergillus, Mycobacterium, etc.).
• Undergone major surgery or sustained severe trauma within 3 months prior to randomization, or plan to undergo surgery during the study period.
• Donated blood or experienced significant blood loss (≥400 mL), received a blood transfusion or used blood products within 3 months prior to randomization, or plan to donate blood or blood components during the study period or within 3 months after the end of the study.
• Have a known allergy to any component of the investigational drug, or a history of allergy to drugs, foods, or other substances.
• Have difficulty with venous blood collection (e.g., unable to tolerate venipuncture, history of needle or blood phobia, poor venous access, etc.).
• Have electrocardiogram abnormalities (e.g., QTcF > 450 ms, shortened or prolonged PR interval, second- or third-degree atrioventricular block, Wolff-Parkinson-White syndrome, etc.) that are considered clinically significant by the investigator.
• Urine drug screen test positive (for morphine, methamphetamine, ketamine, methylenedioxymethamphetamine, tetrahydrocannabinolic acid).
• Alcohol breath test result > 0 mg/100 mL.
• Have a history of hepatitis B, hepatitis C, HIV, or syphilis, or have positive diagnostic test results for hepatitis B, hepatitis C, HIV, or syphilis.
• Have abnormalities in other examinations (physical examination, vital signs, chest X-ray, laboratory tests, etc.) that are considered clinically significant by the investigator.
• Previously received any agent targeting PD-1/PD-L1 or CTLA-4.
• Received any other investigational drug or participated in another interventional clinical trial within 3 months prior to screening.
• Used any medication (including traditional Chinese herbs, health supplements, etc.) within 14 days prior to randomization, or within a period shorter than 5 half-lives of the last medication before the investigational drug administration day, whichever is longer.
• Received a live or live-attenuated vaccine within 3 months prior to randomization, or an inactivated vaccine within 14 days prior to randomization, or plan to receive vaccination during the study period.
• Have a history of drug abuse or use of soft drugs (e.g., cannabis) or hard drugs (e.g., cocaine, phencyclidine, etc.) within 1 year prior to randomization.
• Heavy smokers or have smoked ≥5 cigarettes per day on average within 3 months prior to randomization, or are unwilling to stop using any tobacco products during hospitalization.
• Alcoholics or have a history of regular alcohol consumption within 6 months prior to randomization, i.e., consuming more than 14 units of alcohol per week (1 unit = 360 mL of beer, 45 mL of spirit with 40% alcohol content, or 150 mL of wine); or are unwilling to stop alcohol consumption or any alcohol-containing products during the study period.
• Consume excessive amounts of tea, coffee, and/or caffeinated beverages on average per day (>8 cups, 1 cup = 250 mL), or do not agree to refrain from consuming tea, coffee, and/or caffeinated foods, grapefruit (pomelo) and/or grapefruit juice, and/or products containing poppy during the study period.
• Have special dietary requirements (e.g., vegetarian), are unable to comply with a standardized diet, or have lactose intolerance.
• Unable to complete this study or follow the study procedures for any other reason, or are considered by the investigator to have any other condition that makes them unsuitable for participation in this study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Другое

Центры проведения

Китай · 1 центр

• Zhejiang Xiaoshan Hospital — Ханчжоу

Идентификаторы

NCT: NCT07619001 · AK104-103

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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