KXZY-GB18-101(1B) is an extension of KXZY-GB18-101, a first-in-human, dose-escalation trial in healthy adult participants to evaluate the safety, tolerability, PK, PD, and immunogenicity of GB18. As a humanized GDF15 monoclonal antibody, GB18 is expected to improve anorexia and weight loss caused by metabolic disorders driven by overactivation of the GDF15-GFRAL-RET signaling pathways. With favorable readouts of KXZY-GB18-101, this study aims to evaluate the effects of GB18 in patients with tumor cachexia. This open-label, multiple-ascending-dosing study will enroll 18-36 participants into 3 dosing-level cohorts (B1-B3, each with 6-12 participants).
KXZY-GB18-101(1B) is an extension of KXZY-GB18-101, a first-in-human, dose-escalation trial in healthy adult participants to evaluate the safety, tolerability, PK, PD, and immunogenicity of GB18. As a humanized GDF15 monoclonal antibody, GB18 is expected to improve anorexia and weight loss associated with metabolic disorders by targeting the overactivation of GDF15-GFRAL-RET signaling pathways. With favorable readouts of KXZY-GB18-101, KXZY-GB18-101(1B) aims to evaluate the efficacy and safety of GB18 in patients with tumor cachexia. This open-label, multiple-ascending-dosing study will enroll 18-36 participants into 3 dosing-level cohorts (each with 6-12 participants). The treatment and follow-up period will be 12 weeks each. Each participant will undergo safety and efficacy assessments, including vital sign measurements, physical examinations, 12-lead electrocardiograms, and laboratory tests before and after GB18 administration. Blood samples will also be collected to evaluate pharmacokinetic and pharmacodynamic properties, as well as the immunogenicity. The aims of this study include: * To evaluate the safety and tolerability of GB18 after multiple subcutaneous injections of GB18 in Chinese participants with tumor cachexia. * To evaluate the efficacy of multiple subcutaneous injections of GB18 in Chinese participants with tumor cachexia. * To evaluate the PK characteristics of Chinese tumor cachexia participants after multiple subcutaneous injections of GB18. * To evaluate the PD characteristics of Chinese participants with tumor cachexia after multiple subcutaneous injections of GB18. * To evaluate the immunogenicity of multiple subcutaneous injections of GB18 in Chinese participants with tumor cachexia.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
GB18 will be administered via subcutaneous injection with different doses.
Peking University Cancer Hospital
Beijing, Beijing Municipality, China
Beijing GoBroad Hospital
Beijing, Beijing Municipality, China
Incidence of adverse events
The number and severity of adverse events (e.g., abnormalities in laboratory tests, vital signs, physical examinations, and 12-lead ECGs, as assessed by CTCAE v6.0) will be recorded and analyzed.
Time frame: From pre-dosing to the end of follow-up at 24 weeks
Change of the third lumbar vertebra skeletal muscle index (LSMI) from the baseline
The change of the third lumbar vertebra skeletal muscle index (LSMI) from the baseline evaluated by computed tomography scan
Time frame: From pre-dosing to 18 weeks after the first dosage of GB18
Change of body weight compared to baseline
The change of body weight compared to baseline
Time frame: From pre-dosing to the end of follow-up at 24 weeks
Changes from baseline in Functional Assessment of Anorexia/Cachexia Therapy (FAACT) score and its subscales
The changes from baseline in the total score of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) and its subscales
Time frame: From pre-dosing to 18 weeks after the first dosage of GB18
Changes in physical activity and sleep compared to the baseline
Changes in physical activity and sleep will be evaluated by acceleration measurement method via wearable devices
Time frame: From pre-dosing to end of treatment at 12 weeks
Change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS)-Physiological Function Score
Change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS)-Physiological Function Score
Time frame: From pre-dosing to 18 weeks after the first dosage of GB18
Change from baseline in PROMIS-fatigue score
Change from baseline in PROMIS-fatigue score
Time frame: From pre-dosing to 18 weeks after the first dosage of GB18
Tmax of GB18 concentration
Tmax of GB18 concentration
Time frame: From pre-dosing to end of follow-up at 24 weeks
Cmax of GB18
Cmax of GB18
Time frame: From pre-dosing to end of follow-up at 24 weeks
AUC0-t of GB18
AUC0-t of GB18
Time frame: From pre-dosing to end of follow-up at 24 weeks
Serum concentrations of total and unbound (if feasible) GDF15
Serum concentrations of total and, if feasible, unbound GDF15 specified in the schedule of activities.
Time frame: From pre-dosing to end of follow-up at 24 weeks
(if applicable) Incidence of ADA and Nab
(if applicable) Incidence of ADA and Nab
Time frame: From pre-dosing to end of follow-up at 24 weeks
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