Subcutaneous XH-02 treatment for adults with hypoparathyroidism

Efficacy and Safety of Subcutaneous Injection of mRNA Nucleic Acid Drug XH-02 in the Treatment of Adult Hypoparathyroidism

This trial tries a subcutaneous mRNA medicine called XH-02 that makes parathyroid hormone (PTH) to treat adults with chronic hypoparathyroidism.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Peking Union Medical College Hospital (Academic / other)
• Drugs / interventions: radiation, methotrexate
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07530705 on ClinicalTrials.gov

What this trial studies

This Phase 1/2 interventional study tests single and multiple subcutaneous injections of XH-02, an mRNA drug designed to express PTH in the body, in adults with chronic hypoparathyroidism. The protocol enrolls adults 18–65 years with disease lasting at least 26 weeks who have inadequate control with or intolerance to conventional calcium and vitamin D therapy. Endpoints will focus on safety, pharmacodynamic effects on calcium and PTH-related measures, and preliminary efficacy signals following subcutaneous dosing, building on prior intravenous XH-02 data. The design likely uses dose cohorts and monitoring for laboratory and clinical safety outcomes over a defined follow-up period.

Who should consider this trial

Good fit: Adults aged 18–65 with chronic hypoparathyroidism of at least 26 weeks whose condition is not adequately controlled by or who are intolerant to conventional calcium and vitamin D therapy are the intended candidates.

Not a fit: Patients younger than 18 or older than 65, those with well-controlled hypoparathyroidism on standard therapy, or individuals with contraindications to the investigational treatment are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, XH-02 could provide a new way to replace PTH, improve calcium control, and reduce reliance on high-dose oral calcium and active vitamin D.

How similar studies have performed: A completed intravenous XH-02 study showed clear pharmacodynamic effects and good safety in patients, but subcutaneous mRNA PTH delivery is a relatively new approach compared with established recombinant PTH injections.

Eligibility criteria

Inclusion Criteria:

1. Aged 18-65 years (inclusive of 18 and 65), male or female.
2. 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.
3. Inadequate control of hypoparathyroidism with conventional treatment (calcium and vitamin D) or intolerance to such treatment.
4. At screening, Body Mass Index (BMI) of 17-40 kg/m² (inclusive).
5. If aged ≤25 years, radiographic evidence of epiphyseal closure based on X-ray examination of the wrist and hand of the non-dominant hand.

Exclusion Criteria:

1. Impaired response to PTH (pseudohypoparathyroidism), characterized by resistance to PTH and elevated PTH levels during hypocalcemia.
2. Known allergies, or a history of allergy to the investigational drug or polyethylene glycol (PEG).
3. 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.
4. History of vaccination within 4 weeks prior to enrollment, or planned vaccination during the study period.
5. Women who are pregnant or breastfeeding.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.

Where this trial is running

Beijing, Beijing Municipality

• Peking Union Medical College Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Principal investigator: Yan Qin — Peking Union Medical College Hospital
• Study coordinator: Sanxi Ai, Doctor

Conditions Hypoparathyroidism; hypoparathyroidism; XH-02; mRNA