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

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.

Timeline

Start

2025-10-28

Primary completion

2026-01-20

Completion

2026-04-20

Publications

• Background Joo M, Kim D, Lee MW, Lee HJ, Kim JM. GDF15 Promotes Cell Growth, Migration, and Invasion in Gastric Cancer by Inducing STAT3 Activation. Int J Mol Sci. 2023 Feb 2;24(3):2925. doi: 10.3390/ijms24032925.
• Background 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.
• 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.
• Background 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.
• Background 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.
• Background 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.
• Background Tsai VW, Brown DA, Breit SN. Targeting the divergent TGFbeta superfamily cytokine MIC-1/GDF15 for therapy of anorexia/cachexia syndromes. Curr Opin Support Palliat Care. 2018 Dec;12(4):404-409. doi: 10.1097/SPC.0000000000000384.
• Background 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.
• Background 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.
• 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.
• 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.
• 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.
• Background 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.
• Background Naito T. Evaluation of the True Endpoint of Clinical Trials for Cancer Cachexia. Asia Pac J Oncol Nurs. 2019 Jul-Sep;6(3):227-233. doi: 10.4103/apjon.apjon_68_18.
• Background Nishikawa H, Goto M, Fukunishi S, Asai A, Nishiguchi S, Higuchi K. Cancer Cachexia: Its Mechanism and Clinical Significance. Int J Mol Sci. 2021 Aug 6;22(16):8491. doi: 10.3390/ijms22168491.
• Background Li Y, Jin H, Chen Y, Huang T, Mi Y, Zou Z. Cancer cachexia: molecular mechanism and pharmacological management. Biochem J. 2021 May 14;478(9):1663-1688. doi: 10.1042/BCJ20201009.
• Background Argiles JM, Lopez-Soriano FJ, Stemmler B, Busquets S. Cancer-associated cachexia - understanding the tumour macroenvironment and microenvironment to improve management. Nat Rev Clin Oncol. 2023 Apr;20(4):250-264. doi: 10.1038/s41571-023-00734-5. Epub 2023 Feb 20.
• Background Baazim H, Antonio-Herrera L, Bergthaler A. The interplay of immunology and cachexia in infection and cancer. Nat Rev Immunol. 2022 May;22(5):309-321. doi: 10.1038/s41577-021-00624-w. Epub 2021 Oct 4.
• Background Evans WJ, Morley JE, Argiles J, Bales C, Baracos V, Guttridge D, Jatoi A, Kalantar-Zadeh K, Lochs H, Mantovani G, Marks D, Mitch WE, Muscaritoli M, Najand A, Ponikowski P, Rossi Fanelli F, Schambelan M, Schols A, Schuster M, Thomas D, Wolfe R, Anker SD. Cachexia: a new definition. Clin Nutr. 2008 Dec;27(6):793-9. doi: 10.1016/j.clnu.2008.06.013. Epub 2008 Aug 21.

Drugs

Indications

No indication recorded.