A Study to Test the Safety and Blood Levels of PMG1016 in Healthy Adults

Официальное название

A Phase 1a, First-in-human, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of PMG1016 in Healthy Volunteers

Обзор

This study is a first-in-human (FIH), randomized, double-blind, placebo-controlled study of PMG1016 in healthy adult participants. It aims to investigate the safety, tolerability, PK, and immunogenicity of PMG1016 administered via IV infusion. Cohort 1: Healthy participants receiving single doses of PMG1016 Dose 1 or placebo. Cohort 2: Healthy participants receiving single doses of PMG1016 Dose 2 or placebo. Cohort 3: Healthy participants receiving single doses of PMG1016 Dose 3 or placebo. Cohort 4: Healthy participants receiving single doses of PMG1016 Dose 4 or placebo.

Подробное описание

Participants will be enrolled and randomized into 1 of 4 cohorts in a double-blind manner

Вмешательства

• Препарат PMG1016 Dose 1
  Participants will be administered PMG1016 Dose 1 or placebo in a 100 mL IV infusion volume
• Препарат PMG1016 Dose 2
  Participants will be administered PMG1016 Dose 2 or placebo in a 100 mL IV infusion volume
• Препарат PMG1016 Dose 3
  Participants will be administered PMG1016 dose 3 or placebo in a 100 mL IV infusion volume
• Препарат PMG1016 Dose 4
  Participants will be administered PMG1016 dose 4 or placebo in a 100 mL IV infusion volume

Первичные конечные точки

• Treatment-emergent adverse events (TEAEs) [Срок оценки: Day 1 to Day 57]
• Serious adverse events (SAEs) [Срок оценки: From Day 1 to Day 57]
• Number of participants with abnormal pulse rate [Срок оценки: From Day 1 to Day 57]
• Number of participants with abnormal blood pressure [Срок оценки: From Day 1 to Day 57]
• Number of participants with abnormal respiratory rate [Срок оценки: From Day 1 to Day 57]
• Number of participants with abnormal tympanic temperature [Срок оценки: From Day 1 to Day 57]
• Number of Participants with Clinically Significant Abnormal PR Interval [Срок оценки: From Day 1 to Day 57]
• Number of Participants with Clinically Significant Abnormal QRS Duration [Срок оценки: From Day 1 to Day 57]
• Number of Participants with Clinically Significant Abnormal QT interval [Срок оценки: From Day 1 to Day 57]
• Number of Participants with Clinically Significant Abnormal RR interval [Срок оценки: From Day 1 to Day 57]

Вторичные конечные точки (10)

• Incidence of anti-drug antibodies (ADA) [Срок оценки: From Day 1 to Day 57]
• Maximum serum PMG1016 concentration (Cmax) [Срок оценки: Varying timepoints through end of treatment, up to Day 57]
• Time to maximum concentration (Tmax) [Срок оценки: Varying timepoints through end of treatment, up to Day 57]
• Area under the serum drug concentration-time curve (AUC) from time zero to the last time point with measurable concentration (AUC0-t) [Срок оценки: Varying timepoints through end of treatment, up to Day 57]
• AUC from time zero to infinity (AUC0-∞) [Срок оценки: Varying timepoints through end of treatment, up to Day 57]
• The extrapolated portion of AUC0-∞ from Tlast to infinity (%AUCextrap) [Срок оценки: Varying timepoints through end of treatment, up to Day 57]
• Terminal elimination half-life (t1/2) [Срок оценки: Varying timepoints through end of treatment, up to Day 57]
• Apparent total body clearance (CL) [Срок оценки: Varying timepoints through end of treatment, up to Day 57]
• Apparent volume of distribution during the terminal phase (Vz) [Срок оценки: Varying timepoints through end of treatment, up to Day 57]
• Apparent terminal elimination rate constant (λz) [Срок оценки: Varying timepoints through end of treatment, up to Day 57]

Критерии участия

Критерии включения

• Participants must be in good health based on medical history, physical exam, vital signs, ECG, and lab results at screening, as judged by the PI.
• BMI 17.5-32.0 kg/m² and body weight 50-100 kg for males or 45-100 kg for females
• No clinically significant lab abnormalities (hematology, coagulation, biochemistry, urinalysis) per PI discretion
• Females: Must be non-pregnant, non-lactating, and use double contraception (condom + hormonal method/vaginal ring/IUD) through study completion, unless surgically sterile, postmenopausal, or in same-sex relationships. Negative pregnancy tests required. No oocyte donation for 90 days post dose.
• Males: Must be surgically sterile, abstinent, or use condoms plus a highly effective method for female partners. Vasectomized males without proof of azoospermia must use condoms with WOCBP partners. No sperm donation for 90 days post dose.

Критерии исключения

• History or evidence of any clinically significant medical condition (e.g., cardiovascular, gastrointestinal, endocrine, hematologic, psychiatric, renal, musculoskeletal, infectious, neurological, or other major disease) as determined by the PI.
• A PR <40 or >100 bpm or mean SBP >140 mmHg or DBP >95 mmHg (based on triplicate supine measurements after 5 minutes' rest).
• Mean QTcF >450 ms (males) or >470 ms (females) at Screening; one repeat triplicate ECG allowed at PI discretion
• Any clinically significant ECG abnormalities (rhythm, conduction, morphology) that may affect QTc interpretation, per PI judgment
• ALT, AST, or creatinine >1.5 × ULN, or total bilirubin or lymphocytes > ULN.
• Hemoglobin (HGB) below the lower limit of the normal range (ULN) prior to enrollment.
• Participants with a positive toxicology screening panel or positive alcohol breath test at Screening and on Day -1.
• Regular alcohol consumption defined as > 21 alcohol units per week. Participant is unwilling to abstain from alcohol beginning 48 hours prior to admission to the CRU and while residing at the CRU.
• Blood donation or significant blood loss (≥500 mL) within 60 days prior to the first IP administration.
• Plasma donation within 7 days prior to the first IP administration.
• Use of any investigational product/device within 30 days or 5 half-lives (whichever is longer), or participation in >4 investigational drug studies in the past year.
• Pregnant or lactating at Screening or planning pregnancy (self or partner) during the study or follow-up.
• Fever >37.5°C or symptomatic infection within 2 weeks before Screening; any infection requiring systemic antibiotics within 3 months; history of recurrent infections; or a positive SARS-CoV-2 PCR before CRU admission.
• Active malignancy, history of malignancy, or untreated precancerous lesions. Adequately treated or fully excised precancerous lesions are allowed.
• Participants with a known history of retinal diseases, including conditions such as prior retinal detachment.
• Participants with a history of recurrent epistaxis or gingival bleeding.
• Use of prescription medications (except hormonal contraception) within 2 weeks before dosing; mAb products within 5 half-lives; or OTC drugs, supplements, or herbal products within 7 days before dosing.
• History of anaphylaxis or severe allergy per PI judgment; mild untreated hay fever may be allowed.
• History of allergic reaction or hypersensitivity to any of the excipients in the IP.
• Positive screening test for HIV-1/2, HBsAg, HCV antibody, or syphilis.
• Any condition that, in the PI's judgment, may pose a risk to the participant or 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

Австралия · 1 центр

• Nucleus Network (Brisbane) — Brisbane

Идентификаторы

NCT: NCT07615985 · PMG1016-1031

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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