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

NCT07530705 | Recruiting Phase 1

• 1 other identifier: K9040
• Study Type: interventional
• Target: 15
• 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. 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.

Conditions

Hypoparathyroidism

Keywords

hypoparathyroidism; XH-02; mRNA

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 administration), and 4, 8, 12, 18, 24, 30, 36, 48, 60, and 72 hours postdose. Multiple dose: Predose on Day 1 to 5 (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 administration), and 4, 8, 12, 18, 24, 30, 36, 48, 60, and 72 hours postdose. Multiple dose: Predose on Day 1 to 5 (before each dose); and 4, 8, 12, 24, 30, 36, 48, 60, and 72 hours after the last dose

• Serum calcium (efficacy)

  Single dose: Predose (within one hour before administration), and 4, 8, 12, 24, 36, 48, and 72 hours postdose. Multiple dose: Predose on Day 1 to 5 (before each dose); and 24, 48, and 72 hours after the last dose

• Serum phosphorus (efficacy)

  Single dose: Predose (within one hour before administration), and 4, 8, 12, 24, 36, 48, and 72 hours postdose. Multiple dose: Predose on Day 1 to 5 (before each dose); and 24, 48, and 72 hours after the last dose

• Serum magnesium (efficacy)

  Single dose: Predose (within one hour before administration), and 4, 8, 12, 24, 36, 48, and 72 hours postdose. Multiple dose: Predose on Day 1 to 5 (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 on Day 1 to 5 (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 on Day 1 to 5 (before each dose); and 24, 48, and 72 hours after the last dose

Study Arms (7)

Single dose (40 μg)

EXPERIMENTAL

Participants will receive a single subcutaneous dose of 40 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

Multiple doses (20 µg）

EXPERIMENTAL

Participants will receive a daily subcutaneous injection of 20 µg of XH-02 for 5 consecutive days

Drug: Multiple subcutaneous injection

Multiple doses (40 µg）

EXPERIMENTAL

Participants will receive a daily subcutaneous injection of 40 µg of XH-02 for 5 consecutive days

Drug: Multiple subcutaneous injection

Multiple doses (60 µg）

EXPERIMENTAL

Participants will receive a daily subcutaneous injection of 60 µg of XH-02 for 5 consecutive days

Drug: Multiple subcutaneous injection

Multiple doses (80 µg）

EXPERIMENTAL

Participants will receive a daily subcutaneous injection of 80 µg of XH-02 for 5 consecutive days

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 (40 μg); Single dose (80 μg)

Multiple subcutaneous injection DRUG

Participants will receive once daily subcutaneous injection of XH-02 for 5 consecutive days.

Multiple doses (20 µg）; Multiple doses (40 µg）; Multiple doses (60 µg）; Multiple doses (80 µg）

Eligibility Criteria

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

You may qualify if:

• Aged 18-65 years (inclusive of 18 and 65), male or female.
• A history of postoperative chronic hypoparathyroidism (HP) or autoimmune, genetic, or idiopathic HP for at least 26 weeks. HP is confirmed based on a previous occurrence of hypocalcemia accompanied by an inappropriately low serum parathyroid hormone (PTH) level (below the upper limit of the local laboratory's normal range). Note: If the subject does not have a documented diagnosis of chronic HP but has experienced hypocalcemia accompanied by an inappropriately low serum PTH level for at least 26 weeks prior to screening, and the investigator determines that the diagnosis of chronic HP is met, this criterion is considered fulfilled.
• Inadequate control of hypoparathyroidism with conventional treatment (calcium and vitamin D) or intolerance to such treatment.
• At screening, Body Mass Index (BMI) of 17-40 kg/m² (inclusive).
• If aged ≤25 years, radiographic evidence of epiphyseal closure based on X-ray examination of the wrist and hand of the non-dominant hand.

You may not qualify if:

• Impaired response to PTH (pseudohypoparathyroidism), characterized by resistance to PTH and elevated PTH levels during hypocalcemia.
• Known allergies, or a history of allergy to the investigational drug or polyethylene glycol (PEG).
• 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; history of parathyroid cancer within 5 years prior to screening; acromegaly; or multiple endocrine neoplasia.
• History of vaccination within 4 weeks prior to enrollment, or planned vaccination during the study period.
• Women who are pregnant or breastfeeding.
• Patients with high-risk thyroid cancer requiring TSH suppression to \<0.2 mIU/L within the past 2 years, or those with a history of malignancy.
• Subjects requiring long-term use of diuretics, phosphate binders (except calcium supplements), digoxin, lithium, methotrexate, biotin \>30 μg/day, or systemic corticosteroids (except as replacement therapy). Patients requiring long-term use of hormones or immunosuppressants (e.g., for rheumatic or autoimmune diseases) will not be enrolled in this study. Note: Subjects who can discontinue these medications during the study may be enrolled, but they must be discontinued for at least 5.5 half-lives prior to Visit 1 blood sample collection. Biotin must be discontinued for at least 1 day prior to screening blood sample collection. These medications are prohibited throughout the study.
• Use of PTH-like drugs (either commercially available or obtained through participation in a clinical trial), 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 and receipt of investigational drug or device within 8 weeks prior to screening, or still within 5.5 half-lives of the drug from a previously participated trial.
• Presence of uncontrolled hypertension at baseline, or a history of the following cardiovascular or cerebrovascular diseases, including: (1) Unstable angina; (2) Arrhythmia requiring medication or severe arrhythmia; (3) Myocardial infarction; (4) Class III or higher heart failure (per NYHA classification), second-degree or higher atrioventricular block; (5) Cerebral infarction (except lacunar infarction), cerebral hemorrhage, or other such conditions.
• Increased risk of osteosarcoma, for example, having Paget's disease of bone or unexplained elevated alkaline phosphatase, genetic disorders predisposing to osteosarcoma, or previous exposure to high-dose external beam radiation or implant radiotherapy to the skeleton.
• Abnormal laboratory test results meeting any of the following criteria: Blood routine: Neutrophil count (NEUT#) \<1.5×10⁹/L; Platelet count (PLT) \<90×10⁹/L; Hemoglobin (Hb) \<90g/L; Eosinophil count (EOS#) \>0.5×10⁹/L. Liver and kidney function: Total bilirubin or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) exceeding the normal range; eGFR \<60 ml/min/1.73m².
• Any other medical or other condition that, in the investigator's judgment, might affect the conduct of the study or interfere with the study results, or might increase the risk to the subject.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

Related Publications (11)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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, 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

• 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

• 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

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 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: All participants will receive subcutaneous administration of XH-02. Single-dose phase: accelerated titration combined with 3+3 dose-escalation design. Multiple-dose phase: fixed-dose, once-daily administration for 5 days.

Study Record Dates

• First Submitted: April 1, 2026
• First Posted: April 15, 2026
• Study Start: November 17, 2025
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)