Phase 1a Study Assessing Safety, Tolerability, Pharmacokinetics, and Immunogenicity of PMG1016

Korábbi kezelés

• 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.
• 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.
• Participants with a known history of retinal diseases, including conditions such as prior retinal detachment.
• 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.

Más betegség

• 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.
• Active malignancy, history of malignancy, or untreated precancerous lesions. Adequately treated or fully excised precancerous lesions are allowed.
• Participants with a history of recurrent epistaxis or gingival bleeding.
• 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.

Laborértékek

• 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.

Egyéb

• 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
• Participants with a positive toxicology screening panel or positive alcohol breath test at Screening and on Day -1.
• Pregnant or lactating at Screening or planning pregnancy (self or partner) during the study or follow-up.

• 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.