Efficacy and Safety of Subcutaneous Injection of XH-02 in the Treatment of Adult Hypoparathyroidism

Summary

XH-02 is an mRNA nucleic acid drug that expresses PTH in the body following intravenous or subcutaneous injection, providing PTH replacement therapy for patients with hypoparathyroidism. Animal studies have shown pharmacodynamic effects of XH-02, with a favorable safety profile. A clinical study of intravenously administered XH-02 has been completed in patients with hypoparathyroidism, yielding clear pharmacodynamic results and demonstrating good safety. This study aims to evaluate the safety and efficacy of subcutaneously injected XH-02 in patients with hypoparathyroidism.

Timeline

Start

2025-11-17

Primary completion

2026-05-31

Completion

2026-06-30

Publications

• Background Cao J, Choi M, Guadagnin E, Soty M, Silva M, Verzieux V, Weisser E, Markel A, Zhuo J, Liang S, Yin L, Frassetto A, Graham AR, Burke K, Ketova T, Mihai C, Zalinger Z, Levy B, Besin G, Wolfrom M, Tran B, Tunkey C, Owen E, Sarkis J, Dousis A, Presnyak V, Pepin C, Zheng W, Ci L, Hard M, Miracco E, Rice L, Nguyen V, Zimmer M, Rajarajacholan U, Finn PF, Mithieux G, Rajas F, Martini PGV, Giangrande PH. mRNA therapy restores euglycemia and prevents liver tumors in murine model of glycogen storage disease. Nat Commun. 2021 May 25;12(1):3090. doi: 10.1038/s41467-021-23318-2.
• Background Rejnmark L, Ayodele O, Lax A, Mu F, Swallow E, Gosmanova EO. The risk of chronic kidney disease development in adult patients with chronic hypoparathyroidism treated with rhPTH(1-84): A retrospective cohort study. Clin Endocrinol (Oxf). 2023 Apr;98(4):496-504. doi: 10.1111/cen.14813. Epub 2022 Aug 28.
• Background Chen KS, Gosmanova EO, Curhan GC, Ketteler M, Rubin M, Swallow E, Zhao J, Wang J, Sherry N, Krasner A, Bilezikian JP. Five-year Estimated Glomerular Filtration Rate in Patients With Hypoparathyroidism Treated With and Without rhPTH(1-84). J Clin Endocrinol Metab. 2020 Oct 1;105(10):e3557-65. doi: 10.1210/clinem/dgaa490.
• Background Khan AA, Koch CA, Van Uum S, Baillargeon JP, Bollerslev J, Brandi ML, Marcocci C, Rejnmark L, Rizzoli R, Shrayyef MZ, Thakker R, Yildiz BO, Clarke B. Standards of care for hypoparathyroidism in adults: a Canadian and International Consensus. Eur J Endocrinol. 2019 Mar;180(3):P1-P22. doi: 10.1530/EJE-18-0609.
• Background Khan AA, Rubin MR, Schwarz P, Vokes T, Shoback DM, Gagnon C, Palermo A, Marcocci C, Clarke BL, Abbott LG, Hofbauer LC, Kohlmeier L, Pihl S, An X, Eng WF, Smith AR, Ukena J, Sibley CT, Shu AD, Rejnmark L. Efficacy and Safety of Parathyroid Hormone Replacement With TransCon PTH in Hypoparathyroidism: 26-Week Results From the Phase 3 PaTHway Trial. J Bone Miner Res. 2023 Jan;38(1):14-25. doi: 10.1002/jbmr.4726. Epub 2022 Nov 12.
• Background Karpf DB, Pihl S, Mourya S, Mortensen E, Kovoor E, Markova D, Leff JA. A Randomized Double-Blind Placebo-Controlled First-In-Human Phase 1 Trial of TransCon PTH in Healthy Adults. J Bone Miner Res. 2020 Aug;35(8):1430-1440. doi: 10.1002/jbmr.4016. Epub 2020 Apr 16.
• Background Gosmanova EO, Ayodele O, Chen K, Cook EE, Mu F, Young JA, Rejnmark L. Association of Calcium and Phosphate Levels with Incident Chronic Kidney Disease in Patients with Hypoparathyroidism: A Retrospective Case-Control Study. Int J Endocrinol. 2022 Nov 2;2022:6078881. doi: 10.1155/2022/6078881. eCollection 2022.
• Background Gosmanova EO, Chen K, Rejnmark L, Mu F, Swallow E, Briggs A, Ayodele O, Sherry N, Ketteler M. Risk of Chronic Kidney Disease and Estimated Glomerular Filtration Rate Decline in Patients with Chronic Hypoparathyroidism: A Retrospective Cohort Study. Adv Ther. 2021 Apr;38(4):1876-1888. doi: 10.1007/s12325-021-01658-1. Epub 2021 Mar 9.
• Background Gosmanova EO, Houillier P, Rejnmark L, Marelli C, Bilezikian JP. Renal complications in patients with chronic hypoparathyroidism on conventional therapy: a systematic literature review : Renal disease in chronic hypoparathyroidism. Rev Endocr Metab Disord. 2021 Jun;22(2):297-316. doi: 10.1007/s11154-020-09613-1. Epub 2021 Feb 18.
• Background Khan AA, Bilezikian JP, Brandi ML, Clarke BL, Gittoes NJ, Pasieka JL, Rejnmark L, Shoback DM, Potts JT, Guyatt GH, Mannstadt M. Evaluation and Management of Hypoparathyroidism Summary Statement and Guidelines from the Second International Workshop. J Bone Miner Res. 2022 Dec;37(12):2568-2585. doi: 10.1002/jbmr.4691. Epub 2022 Nov 14.
• Background Shoback DM, Bilezikian JP, Costa AG, Dempster D, Dralle H, Khan AA, Peacock M, Raffaelli M, Silva BC, Thakker RV, Vokes T, Bouillon R. Presentation of Hypoparathyroidism: Etiologies and Clinical Features. J Clin Endocrinol Metab. 2016 Jun;101(6):2300-12. doi: 10.1210/jc.2015-3909. Epub 2016 Mar 4.

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