An Cohort Study on the Safety and Efficacy of XH-02 in Treating Hypoparathyroidism

NCT07540286 | Recruiting Phase 2 DMC

• 1 other identifier: K10348
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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. Previous clinical studies have demonstrated the safety of subcutaneously administered XH-02 in several patients with hypoparathyroidism and have yielded clear efficacy results. This study aims to further validate the safety and efficacy of subcutaneously injected XH-02 in the treatment of hypoparathyroidism in a expanded cohort.

Conditions

Hypoparathyroidism

Keywords

hypoparathyroidism; XH-02; mRNA drug

Outcome Measures

Primary Outcomes (1)

• Adverse events (safety)

  Adverse events, including serious adverse events. Assessment methods: spontaneous reports; scheduled laboratory tests (hematology, chemistry, C-reactive protein, urinalysis); vital signs (blood pressure, heart rate, respiratory rate, temparature), physical examinations, and electrocardiogram (QTc interval, arrhythmia).

  From the first dose through 30 days after the last dose for non-serious adverse events, and through 3 months after the last dose for severe adverse events.

Secondary Outcomes (8)

• PTH(1-84) (efficacy)

  Single dose: Predose (within one hour before dosing) and 4, 8, 12, 18, 24, 30, 36, 48, 60, and 72 hours postdose. Multiple dose: Predose (within one hour before each dose) and 4, 8, 12, 24, 30, 36, 48, 60, and 72 hours after the last dose.

• PTH (efficacy)

  Single dose: Predose (within one hour before dosing) and 4, 8, 12, 18, 24, 30, 36, 48, 60, and 72 hours postdose.

• Serum calcium (efficacy)

  Single dose: Predose (within one hour before dosing), and 4, 8, 12, 24, 36, 48, and 72 hours postdose. Multiple dose: Predose (within one hour before each dose) and 24, 48, and 72 hours after the last dose.

• Serum phosphorus (efficacy)

  Single dose: Predose (within one hour before dosing) and 4, 8, 12, 24, 36, 48, and 72 hours postdose. Multiple dose: Predose (within one hour before each dose) and 24, 48, and 72 hours after the last dose.

• Serum magnesium (efficacy)

  Single dose: Predose (within one hour before dosing) and 4, 8, 12, 24, 36, 48, and 72 hours postdose. Multiple dose: Predose (within one hour before each dose) and 24, 48, and 72 hours after the last dose.

Other Outcomes (2)

• Procollagen type 1 N-terminal propeptide (Exploratory endpoint)

  Multiple dose: Predose (within one hour before each dose) and 24, 48, and 72 hours after the last dose.

• Beta-isomerized C-terminal telopeptide of type 1 collagen (Exploratory endpoint)

  Multiple dose: Predose (within one hour before each dose); and 24, 48, and 72 hours after the last dose.

Study Arms (10)

Single dose: 40 μg

EXPERIMENTAL

Participants will receive a single subcutaneous dose of 40 μg of XH-02

Drug: Single subcutaneous injection

Single dose: 60 μg

EXPERIMENTAL

Participants will receive a single subcutaneous dose of 60 μg of XH-02

Drug: Single subcutaneous injection

Single dose: 80 μg

EXPERIMENTAL

Participants will receive a single subcutaneous dose of 80 μg of XH-02

Drug: Single subcutaneous injection

Single dose: 120 μg

EXPERIMENTAL

Participants will receive a single subcutaneous dose of 120 μg of XH-02

Drug: Single subcutaneous injection

Single dose: 160 μg

EXPERIMENTAL

Participants will receive a single subcutaneous dose of 160 μg of XH-02

Drug: Single subcutaneous injection

Multiple dose: 40 μg

EXPERIMENTAL

Participants will receive 40 μg of XH-02 via subcutaneous injection daily or every other day, for a total of 5 doses.

Drug: Multiple subcutaneous injection

Multiple dose: 60 μg

EXPERIMENTAL

Participants will receive 60 μg of XH-02 via subcutaneous injection daily or every other day, for a total of 5 doses.

Drug: Multiple subcutaneous injection

Multiple dose: 80 μg

EXPERIMENTAL

Participants will receive 80 μg of XH-02 via subcutaneous injection daily or every other day, for a total of 5 doses.

Drug: Multiple subcutaneous injection

Multiple dose: 120 μg

EXPERIMENTAL

Participants will receive 120 μg of XH-02 via subcutaneous injection daily or every other day, for a total of 5 doses.

Drug: Multiple subcutaneous injection

Multiple dose: 160 μg

EXPERIMENTAL

Participants will receive 160 μg of XH-02 via subcutaneous injection daily or every other day, for a total of 5 doses.

Drug: Multiple subcutaneous injection

Interventions

Single subcutaneous injection DRUG

Participants will receive a single dose of XH-02 through subcutaneous injection.

Single dose: 120 μg; Single dose: 160 μg; Single dose: 40 μg; Single dose: 60 μg; Single dose: 80 μg

Multiple subcutaneous injection DRUG

Participants will receive XH-02 via subcutaneous injection daily or every other day, for a total of 5 doses.

Multiple dose: 120 μg; Multiple dose: 160 μg; Multiple dose: 40 μg; Multiple dose: 60 μg; Multiple dose: 80 μg

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years, both males and females eligible;
• History of postoperative chronic HP or autoimmune, genetic, or idiopathic HP for at least 26 weeks. The diagnosis of HP is established based on the presence of inappropriately low serum PTH levels concurrent with hypocalcemia in the past.
• Poorly controlled or intolerant to conventional treatment (calcium and vitamin D) for hypoparathyroidism;
• BMI 17-40 kg/m² (inclusive) at screening;
• If age ≤25 years, radiographic evidence of epiphyseal closure based on X-ray results of the wrist and palm of the non-dominant hand.

You may not qualify if:

• Impaired PTH response (pseudohypoparathyroidism), characterized by PTH resistance and elevated PTH levels in the presence of hypocalcemia;
• Allergic constitution, or allergy to the investigational drug or polyethylene glycol (PEG)-based drugs;
• Any disease other than HP that may affect calcium metabolism, calcium-phosphorus homeostasis, or PTH levels, such as active hyperthyroidism; Paget's disease of bone; severe hypomagnesemia; type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus (HbA1C \>9%; HbA1C test results from blood samples collected within 12 weeks prior to screening are acceptable); severe and chronic liver or kidney disease; Cushing's syndrome; multiple myeloma; active pancreatitis; malnutrition; rickets; recent prolonged immobilization; active malignancy (except for low-risk well-differentiated thyroid cancer or non-melanoma skin cancer); active hyperparathyroidism; parathyroid carcinoma occurring within 5 years prior to screening; acromegaly; or multiple endocrine neoplasia;
• Pregnant or breastfeeding women;
• Male partners with female partners planning to become pregnant, or partners of childbearing potential who are unwilling to use adequate contraceptive methods during the study period;
• Patients with high-risk thyroid cancer requiring TSH suppression to \<0.2 mIU/L within 2 years, or those with a history of tumors;
• Use of loop diuretics, phosphate binders (except calcium supplements), digoxin, lithium, methotrexate, biotin \>30 mcg/day, or systemic corticosteroids (except as replacement therapy);
• Use of PTH-like drugs (whether commercially available or obtained through participation in clinical trials), including PTH(1-84), PTH(1-34), or other N-terminal fragments or analogs of PTH, or PTH-related protein within 4 weeks prior to screening;
• Participation in any other interventional trial receiving investigational drugs or devices within 8 weeks prior to screening, or still within 5.5 half-lives of the investigational drug from the trial in which they participated;
• Presence of uncontrolled hypertension at baseline, or a history of the following cardiovascular or cerebrovascular diseases, including: (1) unstable angina; (2) cardiac arrhythmias requiring medication or severe arrhythmias; (3) myocardial infarction; (4) heart failure class III or higher (NYHA classification), second-degree or higher atrioventricular block; (5) cerebral infarction (excluding lacunar infarction), cerebral hemorrhage, or other such diseases;
• Increased risk of osteosarcoma, such as having Paget's disease of bone or unexplained elevated alkaline phosphatase, having genetic disorders predisposing to osteosarcoma, or having a prior history of extensive external beam or implant radiation therapy involving bone;
• Disease processes that adversely affect gastrointestinal absorption, including but not limited to short bowel syndrome, significant small bowel resection, gastric bypass surgery, tropical sprue, active celiac disease, active ulcerative colitis, active Crohn's disease, gastroparesis, and autoimmune regulator gene mutations associated with malabsorption;
• Any medical or other condition that, in the investigator's judgment, may affect the conduct of the study, interfere with the study results, or increase the risk to the subject/study.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, 100730, China

RECRUITING

Related Publications (11)

• 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.

  PMID: 26943721 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.

  PMID: 36054621 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.

  PMID: 33599907 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.

  PMID: 33687651 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.

  PMID: 36389126 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.

  PMID: 32212275 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.

  PMID: 36271471 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.

  PMID: 30540559 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.

  PMID: 32738041 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.

  PMID: 35974422 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.

  PMID: 34035281 BACKGROUND

MeSH Terms

Conditions

Hypoparathyroidism

Interventions

Injections, Subcutaneous

Condition Hierarchy (Ancestors)

Parathyroid Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Injections; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Yan Qin

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

SanXi Ai, Doctor

CONTACT

18811054896; sanxiai@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Single dose: 5 dose groups (40, 60, 80, 120, 160 μg). Multiple doses: 5 dose groups (40, 60, 80, 120, 160 μg), daily or alternate-day dosing.

Study Record Dates

• First Submitted: April 13, 2026
• First Posted: April 20, 2026
• Study Start: April 13, 2026
• Primary Completion (Estimated): April 30, 2030
• Study Completion (Estimated): July 30, 2030
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)