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.
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).
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.
Sequential
Single subcutaneous injection
DrugParticipants will receive a single dose of XH-02 through subcutaneous injection.
Multiple subcutaneous injection
DrugParticipants will receive once daily subcutaneous injection of XH-02 for 5 consecutive days.
7
Treatment groupsSee each treatment group below.
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).
PTH(1-84) (efficacy)
serum PTH(1-84)
PTH (efficacy)
serum PTH
Serum calcium (efficacy)
Serum calcium
Serum phosphorus (efficacy)
Serum phosphorus
Procollagen type 1 N-terminal propeptide (Exploratory endpoint)
Serum Procollagen type 1 N-terminal propeptide (P1NP)
Beta-isomerized C-terminal telopeptide of type 1 collagen (Exploratory endpoint)
Serum Beta-isomerized C-terminal telopeptide of type 1 collagen (β-CTX)
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