First-in-Human Study of ISH0613: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics

Официальное название

A Randomized, Double-Blind, Placebo-Controlled Phase Ia First-in-Human Study to Evaluate the Single Intravenous Administration of ISH0613 in Healthy Subjects

Обзор

The goal of this clinical trial is to learn about a study drug called ISH0613 and how it behaves in healthy adults. This study will also evaluate the safety and tolerability of ISH0613 after a single intravenous (IV) dose. The main questions this study aims to answer are: I. What medical problems (side effects) may occur after receiving ISH0613? How does ISH0613 move through and get processed in the body? II. Does ISH0613 affect certain biological markers related to the immune system? III. Researchers will compare ISH0613 to a placebo (a look-alike substance that contains no active drug) to better understand its effects. Participants will: I. Receive a single intravenous infusion of either ISH0613 or placebo II. Stay in the clinical unit for several days for close monitoring after dosing III. Return to the clinic for follow-up visits over several weeks IV. Provide blood samples for safety checks and laboratory testing V. Be monitored for any side effects throughout the study

Вмешательства

• Препарат ISH0613 for injection
  80, 240, 480, 640 mg; i.v.
• Препарат Placebo
  80, 240, 480, 640 mg; i.v.

Первичные конечные точки

• Number of participants with treatment-emergent adverse events as assessed by CTCAE v6.0 [Срок оценки: baseline through day 57]
• Injection site reactions assessments [Срок оценки: baseline through day 57]

Вторичные конечные точки (9)

• Maximum observed serum concentration (Cmax) [Срок оценки: baseline through day 57]
• Time to reach maximum observed serum concentration (Tmax) [Срок оценки: baseline through day 57]
• AUC from time 0 to the time of the dosing interval (AUC0-t) [Срок оценки: baseline through day 57]
• AUC from time 0 to infinity (AUC₀-∞) [Срок оценки: baseline through day 57]
• Terminal elimination half-life (t1/2) [Срок оценки: baseline through day 57]
• Apparent clearance after extravascular administration (CL/F) [Срок оценки: baseline through day 57]
• Apparent volume of distribution during the terminal elimination phase after extravascular administration (Vd/F) [Срок оценки: baseline through day 57]
• Serum immunoglobulin levels (IgG, IgA, IgM) [Срок оценки: baseline through day 57]
• B cell count [Срок оценки: baseline through day 57]

Критерии участия

Критерии включения

• Healthy Chinese adult subjects, male or female, aged 18 to 45 years (inclusive);
• Body mass index (BMI) between 19.0 and 28.0 kg/m² (inclusive); body weight generally ≥50 kg for males and ≥45 kg for females;
• Male subjects and their partners, or female subjects, must agree to use at least one effective non-pharmacological contraceptive method (e.g., complete abstinence, intrauterine device, partner sterilization) during the study period, and must have no plan for sperm or egg donation;
• Subjects are able to fully understand the purpose, nature, and procedures of the study, including potential adverse reactions, and voluntarily sign the informed consent form (ICF);
• Subjects are able to communicate well with the investigator and are willing and able to comply with all study procedures and requirements.

Критерии исключения

• Known allergy to the investigational product or any of its excipients, or a history of hypersensitivity to monoclonal antibodies;
• History or presence of clinically significant diseases of the cardiovascular, endocrine, nervous, gastrointestinal, respiratory, genitourinary, hematological, immunological, psychiatric, or metabolic systems, or any other condition that may interfere with study results, as judged by the investigator;
• Clinically significant abnormalities in laboratory tests (hematology, urinalysis, biochemistry, coagulation) or auxiliary examinations (chest X-ray, abdominal ultrasound);
• Positive test results for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV-Ab), human immunodeficiency virus (HIV) antibody, or syphilis antibody;
• Receipt of any surgical procedure within 6 months prior to signing the informed consent form, or planned surgery (including cosmetic, dental, or oral surgery) within 2 weeks after the end of the study;
• Alcohol consumption exceeding 14 units per week within 3 months prior to screening (1 unit = 360 mL beer, 150 mL wine, or 45 mL liquor), or positive alcohol breath test at screening or baseline, or inability to abstain from alcohol during the study;
• Average smoking of more than 5 cigarettes per day within 3 months prior to screening;
• History of drug abuse, use of soft drugs (e.g., cannabis) within 3 months prior to screening, or use of hard drugs (e.g., cocaine, phencyclidine) within 1 year prior to screening, or positive drug abuse screening test (including morphine, ketamine, THC-COOH, methamphetamine, MDMA, cocaine);
• Habitual excessive intake within 4 weeks prior to screening of caffeine-containing beverages or foods or substances that may affect drug metabolism, such as coffee (>1100 mL/day), tea (>2200 mL/day), cola (>2200 mL/day), energy drinks (>1100 mL/day), or chocolate (>510 g/day);
• Use of any prescription drugs, over-the-counter medications, or traditional Chinese medicines within 14 days prior to dosing;
• Receipt of any monoclonal antibody therapy within 6 months prior to dosing;
• Vaccination within 3 months prior to dosing, or planned vaccination during the study period;
• Participation in another clinical trial and receipt of investigational drug treatment within 3 months prior to dosing;
• Blood donation or significant blood loss (>400 mL, excluding menstrual loss) within 3 months prior to screening, or receipt of blood transfusion or blood products, or planned blood donation during the study period or within 1 month after study completion;
• Pregnant or lactating women;
• Clinically significant abnormal vital signs (systolic blood pressure <90 mmHg or ≥140 mmHg; diastolic blood pressure <55 mmHg or ≥90 mmHg; heart rate <50 bpm or >100 bpm; body temperature <35.4°C or >37.3°C), or clinically significant ECG abnormalities (QTcF >450 ms for males, >470 ms for females), or clinically significant findings on physical examination, as judged by the investigator;
• Presence of infection requiring treatment for acute or chronic infection, including but not limited to:

• Herpes zoster within 12 months prior to screening;
• Current suppressive therapy for chronic infections (e.g., tuberculosis, Pneumocystis, cytomegalovirus, herpes simplex virus, varicella-zoster virus, or atypical mycobacteria);
• History of tuberculosis or contact with active tuberculosis within 6 months prior to screening, or positive T-SPOT test;
• Parasitic infection within 3 months prior to dosing;
• Hospitalization due to infectious disease within 30 days prior to dosing;
• Parenteral anti-infective treatment (including antibacterial, antiviral, antifungal, or antiparasitic agents) within 30 days prior to dosing;
• Any other condition that, in the opinion of the investigator, makes the subject unsuitable for participation in the study.

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

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Affiliated Drum Tower Hospital, Medical School of Nanjing University — Нанкин

Идентификаторы

NCT: NCT07516639 · ISH0613-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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