Chronic Kidney Disease
Conditions
Brief summary
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.
Detailed description
Participants will be enrolled and randomized into 1 of 4 cohorts in a double-blind manner
Interventions
DRUGPMG1016 Dose 1
Participants will be administered PMG1016 Dose 1 or placebo in a 100 mL IV infusion volume
DRUGPMG1016 Dose 2
Participants will be administered PMG1016 Dose 2 or placebo in a 100 mL IV infusion volume
DRUGPMG1016 Dose 3
Participants will be administered PMG1016 dose 3 or placebo in a 100 mL IV infusion volume
DRUGPMG1016 Dose 4
Participants will be administered PMG1016 dose 4 or placebo in a 100 mL IV infusion volume
Sponsors
Pulmongene Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-emergent adverse events (TEAEs) | Day 1 to Day 57 | The incidence and severity occurred |
| Serious adverse events (SAEs) | From Day 1 to Day 57 | The incidence and severity occurred |
| Number of participants with abnormal pulse rate | From Day 1 to Day 57 | — |
| Number of participants with abnormal blood pressure | From Day 1 to Day 57 | — |
| Number of participants with abnormal respiratory rate | From Day 1 to Day 57 | — |
| Number of participants with abnormal tympanic temperature | From Day 1 to Day 57 | — |
| Number of Participants with Clinically Significant Abnormal PR Interval | From Day 1 to Day 57 | — |
| Number of Participants with Clinically Significant Abnormal QRS Duration | From Day 1 to Day 57 | — |
| Number of Participants with Clinically Significant Abnormal QT interval | From Day 1 to Day 57 | — |
| Number of Participants with Clinically Significant Abnormal RR interval | From Day 1 to Day 57 | — |
| Number of Participants with Clinically Significant Valvular Abnormalities | Day 1 to Day 29 | The number of participants with clinically significant valvular abnormalities identified by transthoracic echocardiography (TTE) |
| Number of Participants with Clinically Significant Abnormal Left Ventricular Ejection Fraction | Day 1 to Day 29 | The number of participants with clinically significant abnormalities in left ventricular ejection fraction (LVEF) assessed by transthoracic echocardiography (TTE) |
| Number of Participants with Clinically Significant Abnormal Hematology Results | Day 1 to Day 57 | — |
| Number of Participants with Clinically Significant Abnormal Clinical Chemistry Results | Day 1 to Day 57 | — |
| Number of Participants with Clinically Significant Abnormal Urinalysis Results | Day 1 to Day 57 | — |
| Number of Participants with Clinically Significant Abnormal Physical Examination Findings | Day 1 to Day 57 | assessment of general appearance; head; ears; eyes; nose; throat; dentition; thyroid; chest (heart and lungs); abdomen; skin; neurological system; extremities; back; neck; musculoskeletal system; and lymph nodes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of anti-drug antibodies (ADA) | From Day 1 to Day 57 | Percentage of PMG1016-induced ADA positive participants and percentage of PMG1016-boosted ADA positive participants |
| Maximum serum PMG1016 concentration (Cmax) | Varying timepoints through end of treatment, up to Day 57 | Determine PMG1016 Cmax in Serum |
| Time to maximum concentration (Tmax) | Varying timepoints through end of treatment, up to Day 57 | Determine PMG1016 Tmax in Serum. |
| Area under the serum drug concentration-time curve (AUC) from time zero to the last time point with measurable concentration (AUC0-t) | Varying timepoints through end of treatment, up to Day 57 | Determine PMG1016 AUC and AUC0-t in Serum. |
| AUC from time zero to infinity (AUC0-∞) | Varying timepoints through end of treatment, up to Day 57 | Determine PMG1016 AUC0-∞ in Serum. |
| The extrapolated portion of AUC0-∞ from Tlast to infinity (%AUCextrap) | Varying timepoints through end of treatment, up to Day 57 | Determine PMG1016 %AUCextrap in Serum. |
| Terminal elimination half-life (t1/2) | Varying timepoints through end of treatment, up to Day 57 | Determine PMG1016 t1/2 in Serum. |
| Apparent total body clearance (CL) | Varying timepoints through end of treatment, up to Day 57 | Determine PMG1016 CL in Serum. |
| Apparent volume of distribution during the terminal phase (Vz) | Varying timepoints through end of treatment, up to Day 57 | Determine PMG1016 Vz in Serum. |
| Apparent terminal elimination rate constant (λz) | Varying timepoints through end of treatment, up to Day 57 | Determine PMG1016 λz in Serum. |
Countries
Australia
Contacts
CONTACTYaohui Wang
Outcome results
None listed