Phase 1 Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TRT-448 in Healthy Adult Subjects

Официальное название

A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TRT-448 in Healthy Adult Subjects

Обзор

Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TRT-448 in Healthy Adult Subjects

Подробное описание

This is a randomized, double-blind, placebo-controlled first-in-human (FIH) study of TRT-448 conducted in healthy adult participants. Key safety and tolerability assessments of TRT-448 will be regularly reviewed by an appointed Safety Review Committee (SRC). The study will be conducted in 2 parts: single ascending dose (SAD) and multiple ascending dose (MAD) healthy adult subject cohorts. Eligible subjects will be enrolled into a SAD cohort and will be randomized to receive a single dose of TRT-448 or placebo in a 3:1 ratio, respectively, via oral administration. Eligible participants will be enrolled into MAD cohorts and randomized to receive TRT-448 or placebo in a 3:1 ratio, respectively, once daily (QD) via oral administration from Day 1 and through Day 14 (MAD escalation cohorts) or from Day 1 through Day 28 (MAD expansion cohorts), inclusive. A total of up to 144 participants are planned to be enrolled. Each subject will be assessed for safety, pharmacokinetics and pharmacodynamics of TRT-448.

Вмешательства

• Препарат TRT-448
  Investigational drug modulates immune cells for the treatment of inflammatory disease
• Препарат Placebo
  Inert placebo utilized as control

Первичные конечные точки

• Safety and tolerability of TRT-448 in healthy participants [Срок оценки: Day 1 to Day 28]

Вторичные конечные точки (4)

• Cmax [Срок оценки: Day 1 to Day 28]
• Tmax [Срок оценки: Day 1 to Day 28]
• AUClast [Срок оценки: Day 1 to Day 28]
• t1/2 [Срок оценки: Day 1 to Day 28]

Критерии участия

Критерии включения

• Medically healthy , as determined by pre-study medical history, and without clinically significant abnormalities
• Adult males and females, 18 to 55 years of age (inclusive) at screening
• Body mass index (BMI) between 18 and 32 kg/m2 (inclusive) with body weight: ≥ 70 kg for the SAD 1 cohort; ≥ 50 kg for all other cohorts
• Willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions

Критерии исключения

• History of anaphylaxis or other significant allergy which would interfere with the volunteer's ability to participate in the study, including severe Types I-IV hypersensitivity reactions, cytokine release syndrome, or allergic reactions to multiple drugs
• History or presence of cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal cholecystectomy, irritable bowel syndrome, inflammatory bowel disease, etc.), esophageal, endocrine, immunologic, autoimmune and/or inflammatory disease, dermatologic, psychiatric, or neurological disease/disorder
• History of surgery or hospitalization within 3 months prior to screening, or surgery planned during the study.
• Any history of malignant disease in the last 10 years, including leukemia, lymphoma or any significant hematology/oncology disease.

Note: Participants with curatively resected non-melanoma skin cancers >2 years prior to screening or curatively excised cervical carcinoma in situ > 5 years prior to screening are not excluded.

• Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia.
• History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death or screening QTcF > 450 msec in males or > 470 msec in female) or a known arrhythmia (Note: asymptomatic first-degree heart block is not exclusionary).
• Presence or having sequelae of gastrointestinal, liver (including Gilbert's syndrome), kidney, gallbladder, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
• Liver function test results elevated more than 1.3-fold above the upper limit of normal (ULN) for gamma glutamyl transferase (GGT), bilirubin (total), alkaline phosphatase (ALP), aspartate aminotransferase (AST) or alanine aminotransferase (ALT).
• Estimated glomerular filtration rate (eGFR) < 80 mL/min/1.73m2 using the 2021 CKD-EPI creatinine equation.
• Positive test results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at the screening visit.

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

Тройное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07745751 · TRT-448-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗