To Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of GB18 Injection in Healthy Participants

NCT07237464 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: KXZY-GB18-101
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cancer Cachexia (CC); Cancer Cachexia; Cancer Cachexia Syndrome

Keywords

Cancer cachexia; GB18; healthy adult; Phase I; pharmacokinetics; pharmacodynamics

Outcome Measures

Primary Outcomes (1)

• 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.

  From pre-dosing to the end of follow-up at 18 weeks

Secondary Outcomes (3)

• Serum pharmacokinetics parameters (Cmax, Tmax, AUC0-inf, AUC0-t, λz, t1/2, Vz/F, and CL/F).

  From pre-dosing to the end of follow-up at 18 weeks

• Serum concentrations of total and, if feasible, unbound GDF15 specified in the schedule of activities.

  From pre-dosing to the end of follow-up at 18 weeks

• (if applicable) Incidence of ADA and Nab

  From pre-dosing to the end of follow-up at 18 weeks

Other Outcomes (2)

• Change from baseline of body weight at time points specified in the schedule of activities

  From pre-dosing to the end of follow-up at 18 weeks

• Change of QTc interval in the electrocardiogram and its correlation with the dosage of GB18

  From pre-dosing to D71 after dosing

Study Arms (10)

A1-50mg-GB18

EXPERIMENTAL

Drug: GB18 injection

A1-50mg-placebo

PLACEBO COMPARATOR

Drug: Placebo

A2-100mg-GB18

EXPERIMENTAL

Drug: GB18 injection

A2-100mg-placebo

PLACEBO COMPARATOR

Drug: Placebo

A3-200mg-GB18

EXPERIMENTAL

Drug: GB18 injection

A3-200mg-placebo

PLACEBO COMPARATOR

Drug: Placebo

A4-400mg-GB18

EXPERIMENTAL

Drug: GB18 injection

A4-400mg-placebo

PLACEBO COMPARATOR

Drug: Placebo

A5-600mg-GB18

EXPERIMENTAL

Drug: GB18 injection

A5-600mg-placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

GB18 injection DRUG

GB18 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.

A1-50mg-GB18; A2-100mg-GB18; A3-200mg-GB18; A4-400mg-GB18; A5-600mg-GB18

Placebo DRUG

Placebo will be administered to participants at doses matching GB18.

A1-50mg-placebo; A2-100mg-placebo; A3-200mg-placebo; A4-400mg-placebo; A5-600mg-placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Participants (including their partners) who have no plan to become pregnant and voluntarily use effective contraception from screening to 6 months after the last dose.

You may not qualify if:

• 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.
• Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior, or other conditions that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Smoking more than five cigarettes per day on average, or habitually used nicotine containing products, or unable to refrain from smoking during the trial.
• Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention.
• Exposure to live vaccines within 28 days of screening.
• Previous administration with an investigational drug within 30 days or marketed or investigational monoclonal antibodies within 3 months or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).
• History of drug abuse within the past 5 years or use of drugs in the 3 months prior to screening, or a positive urine drug test at screening.
• Screening BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility.
• Screening 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, baseline QTcF interval \>450 msec, or QRS interval \>120 msec). If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF or QRS values should be used to determine the participant's eligibility.
• Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat test, if deemed necessary:
• AST or ALT level ≥1.5 × ULN,
• Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN.

Sponsors & Collaborators

• Shenzhen Kexing Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Beijing GoBroad Hospital

Beijing, Beijing Municipality, China

RECRUITING

Related Publications (19)

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• Tsui KH, Hsu SY, Chung LC, Lin YH, Feng TH, Lee TY, Chang PL, Juang HH. Growth differentiation factor-15: a p53- and demethylation-upregulating gene represses cell proliferation, invasion, and tumorigenesis in bladder carcinoma cells. Sci Rep. 2015 Aug 7;5:12870. doi: 10.1038/srep12870.

  PMID: 26249737 BACKGROUND

• Lerner L, Hayes TG, Tao N, Krieger B, Feng B, Wu Z, Nicoletti R, Chiu MI, Gyuris J, Garcia JM. Plasma growth differentiation factor 15 is associated with weight loss and mortality in cancer patients. J Cachexia Sarcopenia Muscle. 2015 Dec;6(4):317-24. doi: 10.1002/jcsm.12033. Epub 2015 Apr 30.

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• Suzuki H, Mitsunaga S, Ikeda M, Aoyama T, Yoshizawa K, Yoshimatsu H, Kawai N, Masuda M, Miura T, Ochiai A. Clinical and Tumor Characteristics of Patients with High Serum Levels of Growth Differentiation Factor 15 in Advanced Pancreatic Cancer. Cancers (Basel). 2021 Sep 28;13(19):4842. doi: 10.3390/cancers13194842.

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• Niu Y, Zhang W, Shi J, Liu Y, Zhang H, Lin N, Li X, Qin L, Yang Z, Su Q. The Relationship Between Circulating Growth Differentiation Factor 15 Levels and Diabetic Retinopathy in Patients With Type 2 Diabetes. Front Endocrinol (Lausanne). 2021 Mar 15;12:627395. doi: 10.3389/fendo.2021.627395. eCollection 2021.

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• Siddiqui JA, Pothuraju R, Khan P, Sharma G, Muniyan S, Seshacharyulu P, Jain M, Nasser MW, Batra SK. Pathophysiological role of growth differentiation factor 15 (GDF15) in obesity, cancer, and cachexia. Cytokine Growth Factor Rev. 2022 Apr;64:71-83. doi: 10.1016/j.cytogfr.2021.11.002. Epub 2021 Nov 17.

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• Wischhusen J, Melero I, Fridman WH. Growth/Differentiation Factor-15 (GDF-15): From Biomarker to Novel Targetable Immune Checkpoint. Front Immunol. 2020 May 19;11:951. doi: 10.3389/fimmu.2020.00951. eCollection 2020.

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• Grande AJ, Silva V, Sawaris Neto L, Teixeira Basmage JP, Peccin MS, Maddocks M. Exercise for cancer cachexia in adults. Cochrane Database Syst Rev. 2021 Mar 18;3(3):CD010804. doi: 10.1002/14651858.CD010804.pub3.

  PMID: 33735441 BACKGROUND

• Balstad TR, Brunelli C, Pettersen CH, Schonberg SA, Skorpen F, Fallon M, Kaasa S, Bye A, Laird BJA, Stene GB, Solheim TS. Power Comparisons and Clinical Meaning of Outcome Measures in Assessing Treatment Effect in Cancer Cachexia: Secondary Analysis From a Randomized Pilot Multimodal Intervention Trial. Front Nutr. 2021 Jan 14;7:602775. doi: 10.3389/fnut.2020.602775. eCollection 2020.

  PMID: 33585533 BACKGROUND

• Argiles JM, Stemmler B, Lopez-Soriano FJ, Busquets S. Inter-tissue communication in cancer cachexia. Nat Rev Endocrinol. 2018 Dec;15(1):9-20. doi: 10.1038/s41574-018-0123-0.

  PMID: 30464312 BACKGROUND

• Ferrer M, Anthony TG, Ayres JS, Biffi G, Brown JC, Caan BJ, Cespedes Feliciano EM, Coll AP, Dunne RF, Goncalves MD, Grethlein J, Heymsfield SB, Hui S, Jamal-Hanjani M, Lam JM, Lewis DY, McCandlish D, Mustian KM, O'Rahilly S, Perrimon N, White EP, Janowitz T. Cachexia: A systemic consequence of progressive, unresolved disease. Cell. 2023 Apr 27;186(9):1824-1845. doi: 10.1016/j.cell.2023.03.028.

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• Yu J, Choi S, Park A, Do J, Nam D, Kim Y, Noh J, Lee KY, Maeng CH, Park KS. Bone Marrow Homeostasis Is Impaired via JAK/STAT and Glucocorticoid Signaling in Cancer Cachexia Model. Cancers (Basel). 2021 Mar 2;13(5):1059. doi: 10.3390/cancers13051059.

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  PMID: 18718696 BACKGROUND

MeSH Terms

Interventions

alkaloid GB18

Central Study Contacts

Kangsheng Yang

CONTACT

400-888-9496; yangkangsheng@kexing.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double-blind study and thus the Investigator, Sponsor, Sponsor's delegates (if applicable), and participants are all blinded to treatments. No individual participant information that can be potentially unblinded for the Investigator or participant will be reported until the end of the study.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2025
• First Posted: November 19, 2025
• Study Start: October 28, 2025
• Primary Completion: January 20, 2026
• Study Completion: April 20, 2026
• Last Updated: November 19, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)