Efficacy and Safety of XH02 for the Treatment of Hypoparathyroidism (XH02)

Efficacy and Safety of mRNA Drug XH02 in the Treatment of Adult Hypoparathyroidism

This study aims to evaluate the safety and efficacy of a novel PTH replacement therapy drug in patients with hypoparathyroidism. The drug is an mRNA drug which will be translated into PTH after intravenous administration, to achieve the therapeutic effect.

Study Overview

• Status: Recruiting
• Conditions: Hypoparathyroidism
• Intervention / Treatment: Drug: intravenous administration of PTH1-84 mRNA

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100730
    • Recruiting
    • Peking Union Medical College Hospital
    • Contact: SanXi Ai, Doctor; Phone Number: 010-69156874; Email: sanxiai@163.com
    • Principal Investigator: Yan Qin, Doctor
    • Principal Investigator: Ou Wang, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 to 65 years (inclusive), male or female.
• Documented history of post-surgical chronic HP or autoimmune, genetic, or idiopathic HP for at least 26 weeks. Diagnosis of HP is confirmed based on a history of hypocalcemia accompanied by an inappropriately low serum PTH level (below the upper limit of the normal range of the local laboratory). * Note: If a subject lacks documented diagnosis of chronic HP but has exhibited hypocalcemia accompanied by an inappropriately low serum PTH level for at least 26 weeks prior to screening, and is judged by the investigator to meet the diagnostic criteria for chronic HP, they will be considered eligible for this criterion.
• Poorly controlled or intolerant to conventional therapy (calcium and active vitamin D).
• Body Mass Index (BMI) of 17 to 40 kg/m² (inclusive) at screening.
• If aged ≤ 25 years, radiological evidence of closed epiphyses based on X-ray of the non-dominant hand (wrist and palm).

Exclusion Criteria:

• Impaired PTH response (pseudohypoparathyroidism), characterized by PTH resistance and elevated PTH levels in the presence of hypocalcemia.
• History of allergic predisposition, or known allergy to the investigational drug or polyethylene glycol (PEG)-containing medications.
• Any disease other than HP that may affect calcium metabolism, calcium-phosphate 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 (HbA1c >9%; HbA1c results from 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 carcinoma within 5 years prior to screening; acromegaly; or multiple endocrine neoplasia syndromes.
• History of vaccination within 4 weeks prior to enrollment, or planned vaccination during the study period.
• Pregnant or lactating women.
• Patients with high-risk thyroid cancer requiring TSH suppression <0.2 mIU/L within the past 2 years, or patients with a history of malignancy.
• Requirement for long-term use of the following medications: 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 rheumatologic/autoimmune diseases) are excluded. *Note: Subjects who can discontinue these medications for the study may be enrolled, provided the medications are stopped for at least 5.5 half-lives prior to blood sampling at Visit 1. Biotin must be stopped for at least 1 day prior to blood sampling during the screening period. These medications are prohibited throughout the entire study.*
• Use of PTH-like drugs (whether commercially available or obtained through participation in a clinical trial), including PTH(1-84), PTH(1-34), other N-terminal fragments or analogs of PTH, or PTH-related protein, within 4 weeks prior to screening.
• Participation in any other interventional trial involving an investigational drug or device within 8 weeks prior to screening, or within 5.5 half-lives of the administered drug from the previous trial (whichever is longer).
• Uncontrolled hypertension at baseline, OR a history of the following cardiovascular and cerebrovascular diseases: (1) Unstable angina; (2) Drug-requiring or severe arrhythmia; (3) Myocardial infarction; (4) Class III or higher heart failure (NYHA classification), or second-degree or higher atrioventricular block; (5) Cerebral infarction (except lacunar infarction), cerebral hemorrhage, or related diseases.
• Increased risk of osteosarcoma, such as Paget's disease of bone or unexplained elevated alkaline phosphatase; hereditary disorders predisposing to osteosarcoma; or patients who have received extensive external beam radiation therapy or implant radiation involving the skeleton.
• Clinically significant abnormal laboratory findings at screening, including any of the following:

Hematology: Neutrophil count (NEUT#) <1.5 × 10⁹/L; Platelet count (PLT) <90 × 10⁹/L; Hemoglobin (Hb) <90 g/L; Eosinophil count (EOS#) >0.5 × 10⁹/L.

Liver and Renal Function: Total bilirubin, Alanine Aminotransferase (ALT), or Aspartate Aminotransferase (AST) above the normal range; estimated Glomerular Filtration Rate (eGFR) <60 mL/min/1.73m².

• Any medical or other condition that, in the judgment of the Investigator, may affect the conduct of the study, interfere with the interpretation of study results, or pose an increased risk to the subject or the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 20ug; PTH1-84 mRNA 20ug	Drug: intravenous administration of PTH1-84 mRNA; intravenous administration of PTH1-84 mRNA
Experimental: 40ug; PTH1-84 mRNA 40ug	Drug: intravenous administration of PTH1-84 mRNA; intravenous administration of PTH1-84 mRNA
Experimental: 80ug; PTH1-84 mRNA 80ug	Drug: intravenous administration of PTH1-84 mRNA; intravenous administration of PTH1-84 mRNA
Experimental: 120ug; PTH1-84 mRNA 120ug	Drug: intravenous administration of PTH1-84 mRNA; intravenous administration of PTH1-84 mRNA
Experimental: 160ug; PTH1-84 mRNA 160ug	Drug: intravenous administration of PTH1-84 mRNA; intravenous administration of PTH1-84 mRNA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AE and SAE	adverse event (AE) and severe adverse event (SAE) via regular vital sign checks， physical examinations, and safety laboratory tests (including complete blood count, blood biochemistry, coagulation profile, C-reactive protein, urinalysis, cardiac ultrasound, and electrocardiogram).	the whole study period including the screening, treatment, and follow-up period. Follow-up period extends to 90 days after administration.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PTH1-84	serum PTH1-84	Before (within 1 hour) and 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours after administration
PTH	serum PTH	Before (within 1 hour) and 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours after administration
serum calcium	serum calcium	Before (within 1 hour) and 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours after administration
Serum magnesium	Serum magnesium	Before (within 1 hour) and 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours after administration
Serum phosphorus	Serum phosphorus	Before (within 1 hour) and 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours after administration
1,25-dihydroxyvitamin D	serum 1,25-dihydroxyvitamin D	Before (within 1 hour) and 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours after administration
Fractional excretion of calcium （FECa)	FECa (%) = (Urine Calcium × Serum Creatinine) / (Serum Calcium × Urine Creatinine) × 100	Before (within 1 hour) and 4 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours after administration
24-hour urinary calcium	24-hour urinary calcium	Before (within 3 days) and 24 hours, 48 hours, 72 hours after administration
Procollagen type I N-terminal propeptide (P1NP)	serum procollagen type I N-terminal propeptide (P1NP)	Before (within 1 hour) and 24 hours, 48 hours, 72 hours after administration
Type I collagen cross-linked C-telopeptide (β-CTX）	serum type I collagen cross-linked C-telopeptide (β-CTX）	Before (within 1 hour) and 24 hours, 48 hours, 72 hours after administration

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2025
• Primary Completion (Estimated): July 15, 2026
• Study Completion (Estimated): July 30, 2026

Study Registration Dates

• First Submitted: September 14, 2025
• First Submitted That Met QC Criteria: September 22, 2025
• First Posted (Actual): September 29, 2025

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: mRNA; hypoparathyroidism; PTH
• Additional Relevant MeSH Terms: Endocrine System Diseases; Parathyroid Diseases; Hypoparathyroidism
• Other Study ID Numbers: K6744

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No