A Study to Investigate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Immunogenicity of AZD1613 in Healthy Participants.

Официальное название

A Phase I Randomized, Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of AZD1613 Following Single and Multiple Dose Administration in Healthy Participants

Обзор

The purpose of the study is to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of AZD1613 in healthy participants, including Japanese and Chinese descent.

Подробное описание

This is a first-in-human, randomized, single-blind, placebo-controlled, single and multiple ascending dose study in healthy participants and will be conducted at a single study center. It consists of two parts: Part A (Single Ascending Dose - SAD) and Part B (Multiple Ascending Dose - MAD).

Part A of the study is a SAD sequential group design study and will consist of Parts A1, A2, and A3. Part A1 is planned to consist of 7 cohorts, Part A2 is planned to consist of one cohort of participants of Chinese descent, and Part A3 is planned to consist of 2 cohorts of participants of Japanese descent.

Parts A1, A2, and A3 of the study will comprise of:

1. A Screening Period of maximum 28 days. 2. A Treatment Period during which each participant will receive a single subcutaneous (SC) or intravenous (IV) dose of either AZD1613 or placebo on Day 1. 3. A Follow-up Period where participants will return to the study center for non-residential visits until Day 105.

Part B of the study will be a MAD sequential group design study. Up to 3 dose levels of AZD1613 are planned to be investigated in 3 cohorts of healthy participants.

Part B of the study will comprise of:

1. A Screening Period of maximum 28 days. 2. Three Treatment Periods during which participants will receive 3 single subcutaneous (SC) or intravenous (IV) doses of AZD1613 or placebo at 28-day intervals (Day 1, Day 29, and Day 57). 3. A Follow-up Period where participants will return to the study center for non-residential visits until Day 161.

Вмешательства

• Препарат AZD1613
  AZD1613 will be administered as either SC injection or IV infusion on Day 1 in Part A and on Days 1, 29 and 57 in Part B of the study.
• Препарат Placebo
  Placebo will be administered as either SC injection or IV infusion on Day 1 in Part A and Days 1, 29 and 57 in Part B of the study.

Первичные конечные точки

• Number of participants with adverse events (AEs) and serious AEs. [Срок оценки: AEs: Part A: From Day 1 to Final Follow-up (Day 105); Part B: From Day 1 to Final Follow-up (Day 161); SAEs: Part A: From Screening (Day -28 to Day -2) to Final Follow-up visit (Day 105) Part B: From Screening (Day -28) to Final Follow-up visit (Day 161)]

Вторичные конечные точки (5)

• Area under concentration-time curve from time 0 to infinity (AUCinf) (Day 1 only) [Срок оценки: Part A: From Day 1 (pre-dose) to Day 105; Part B: From Day 1 (pre-dose) to Day 141]
• Area under concentration-time curve from time 0 to the last quantifiable concentration (AUClast) [Срок оценки: Part A: From Day 1 (pre-dose) to Day 105; Part B: From Day 1 (pre-dose) to Day 141]
• Maximum observed drug concentration (Cmax) [Срок оценки: Part A: From Day 1 (pre-dose) to Day 105; Part B: From Day 1 (pre-dose) to Day 141]
• Incidence of positive anti-drug antibodies (ADAs) against AZD1613 in serum [Срок оценки: Part A: Day 1 (pre-dose), Day 29, Day 57 and Day 105; Part B: Day 1 (pre-dose), Day 29 (pre-dose), Day 57 (pre-dose), Day 85 and Day 161]
• Change from baseline in study-specific biomarker ABC [Срок оценки: Part A: From Day 1 to Day 105; Part B: From Day -1 to Day 161]

Критерии участия

Критерии включения

• Healthy males and females of non-childbearing potential with suitable veins for cannulation or repeated venipuncture.
• Negative pregnancy test at screening and admission (females only).
• Females of non-childbearing potential confirmed by postmenopausal status or irreversible surgical sterilization.
• Sexually active fertile males must use contraception methods from first administration until 3 months after the last follow-up visit.
• Body mass index (BMI) between 18 and 32 kg/m² and weight at least 50 kg.
• Participants of Chinese descent (Part A2) must have both parents and four grandparents who are Chinese.
• Participants of Japanese descent (Part A3) must have both parents and four grandparents who are Japanese.

Критерии исключения

• The history of any clinically important disease or disorder may either put the participant at risk due to participation in the study, influence the results, or affect the participant's ability to participate in the study.
• History or presence of gastrointestinal, hepatic, or renal disease affecting drug absorption, distribution, metabolism, or excretion of drugs.
• Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of first administration.
• Abnormal lab values at screening or admission (e.g., alanine aminotransferase (ALT) > upper limit normal (ULN), aspartate aminotransferase (AST) > ULN, bilirubin > 1.5 × ULN, estimated glomerular filtration rate (eGFR) < 80 mL/min/1.73 m², hemoglobin < lower limit normal \[LLN\]).
• Any clinically important abnormalities in clinical chemistry, hematology, or urinalysis results.
• Any positive result for serum Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb), Hepatitis C virus antibody (HCV Ab) or Human immunodeficiency virus (HIV).
• Abnormal vital signs after 5 minutes supine rest at screening or admission (e.g., systolic BP < 90 mmHg or ≥ 140 mmHg, diastolic BP < 50 mmHg or ≥ 90 mmHg, heart rate < 45 or > 85 bpm).
• Any clinically important abnormalities in rhythm, conduction, or morphology of resting 12-lead Electrocardiogram (ECG) at screening or admission (e.g., prolonged QTcF > 450 ms, shortened QTcF < 340 ms, family history of long QT syndrome).
• Smokers who smoke more than 5 cigarettes per day and cannot adhere to no smoking during residential visits.
• Known or suspected history of alcohol or drug abuse or excessive alcohol intake.
• Positive screen for drugs of abuse or alcohol at screening or admission.
• History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity.
• Use of prescribed or nonprescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, or intake of > 3 × daily recommended levels of vitamins and minerals during the 2 weeks prior to first administration.
• Plasma donation within one month of screening or any blood donation/blood loss > 500 mL during the 3 months prior to screening.
• Received another new chemical entity within 30 days or 5 half-lives (whichever is longest) of first administration.
• Previously received AZD1613.
• Involvement in the planning and/or conduct of the study.
• Judgment by the Investigator that the participant should not participate due to minor medical complaints or non-compliance with study procedures.
• Medical dietary restrictions or inability/unwillingness to comply with meals provided during the stay at the Clinical Unit.
• Inability to communicate reliably with the Investigator.
• Vulnerable participants (e.g., kept in detention, protected adults under guardianship).

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

Простое слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Research Site — Glendale

Идентификаторы

NCT: NCT06995820 · D9050C00001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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