This study is a first-in-human, randomized, double-blind, placebo-controlled, dose-escalation trial in healthy adult participants to evaluate the safety, tolerability, PK, PD, and immunogenicity of GB18.
A total of 36 healthy participants will be enrolled, including 5 dose cohorts (A1-A5) of 50 mg, 100 mg, 200 mg, 400 mg and 600 mg, with 4 participants in Cohort A1, and 8 participants per following cohorts (A2-A5). Participants in each cohort will be randomized to receive GB18 or placebo.
The arms of this study include:
To evaluate the safety and tolerability of GB18 following a single subcutaneous (SC) administered dose in healthy adult participants.
To characterize the serum pharmacokinetics (PK) of GB18 following a single SC administered dose in healthy adult participants.
To characterize the pharmacodynamics (PD) of a single SC administration of GB18 on circulating GDF15 concentrations in healthy adult participants.
To evaluate the immunogenicity profile of GB18 in healthy adult participants. To evaluate the effect of GB18 on body weight in healthy adult participants. To preliminary evaluation of the relationship between GB18 serum concentration and QTc interval after a single SC administration in healthy adult participants.
Participants who have signed the informed consent form (ICF) prior to the study, fully understand the content, procedures, and possible adverse reactions of the study, and are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
Male and female participants aged 18-55 years (inclusive), at the time of signing the ICF.
Body weight ≥ 50 kg for males and ≥ 45 kg for females, with a body mass index (BMI = weight (kg)/height 2 (m) 2) of 18.5-26 kg/m2 (inclusive).
Male and female participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, Vital signs, 12-lead ECG, and laboratory tests.
Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
History of HIV infection, syphilis, hepatitis B, or hepatitis C; positive testing for HIV, syphilis, HBsAg, or HCVAb.
History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody or molecules made of components of monoclonal antibodies.
History of recurrent infections or active infections.
Sequential
GB18 injection
DrugGB18 will be administered to participants at a starting dose of 50 mg and increasing to 100, 200, 400 and 600 mg in sequential dosing cohorts.
Placebo
DrugPlacebo will be administered to participants at doses matching GB18.
10
Treatment groupsSee each treatment group below.
Number of adverse events as assessed by CTCAE v5.0
The number of AEs (e.g., abnormalities in laboratory tests, vital signs, physical examinations, and 12-lead ECGs) will be recorded and analyzed.
Serum pharmacokinetics parameters (Cmax, Tmax, AUC0-inf, AUC0-t, λz, t1/2, Vz/F, and CL/F).
GB18 Serum pharmacokinetics parameters (unbound and total), including but not limited to maximum concentration (Cmax), peak time (Tmax), area under the serum concentration-time curve from time 0 to infinity (AUC0-inf), area under the serum concentration-time curve from time 0 (pre-dose) to the time t (AUC0-t), elimination rate constant (λz), elimination half-life (t1/2), apparent volume of distribution (Vz/F), apparent total serum clearance (CL/F).
Serum concentrations of total and, if feasible, unbound GDF15 specified in the schedule of activities.
(if applicable) Incidence of ADA and Nab
Change from baseline of body weight at time points specified in the schedule of activities
Change of QTc interval in the electrocardiogram and its correlation with the dosage of GB18
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