XH02 (mRNA PTH) treatment for hypoparathyroidism

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

This trial tests whether an intravenous mRNA drug called XH02 can produce parathyroid hormone and help adults with chronic hypoparathyroidism who are not well controlled on calcium and active vitamin D.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 6 (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)
• Trial ID: NCT07197450 on ClinicalTrials.gov

What this trial studies

This early-phase interventional trial gives intravenous PTH1-84 mRNA (XH02) designed to be translated into parathyroid hormone after dosing. Participants are adults with chronic hypoparathyroidism who are poorly controlled on or intolerant to conventional therapy. Dosing will be delivered intravenously with close safety monitoring and repeated laboratory checks including serum calcium and PTH levels. The primary aims are to characterize safety and tolerability and to look for biological signals of effect on calcium homeostasis.

Who should consider this trial

Good fit: Adults aged 18–65 with documented chronic hypoparathyroidism for at least 26 weeks who remain poorly controlled on or intolerant to conventional calcium and active vitamin D therapy are the intended participants.

Not a fit: People under 18 or over 65, those whose hypoparathyroidism is well controlled on standard therapy, or patients unable to travel to the study site are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, XH02 could provide a more physiologic PTH replacement that stabilizes calcium levels and reduces the need for high-dose oral calcium and active vitamin D.

How similar studies have performed: Recombinant PTH replacement has produced clinical benefit in prior studies, but using mRNA to generate PTH in vivo is a novel approach that has not been broadly tested in humans.

Eligibility criteria

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).
* Conventional therapy (including vitamin D or magnesium supplements, if applicable) can be optimized during the screening period to achieve the following target serum levels: 25(OH) Vitamin D level: 10 - 100 ng/mL (25 - 250 nmol/L, inclusive). Blood magnesium level: Within the normal range or slightly below, i.e., ≥ 1.3 mg/dL (≥ 0.53 mmol/L). Albumin-corrected serum calcium (sCa) level: Within the normal range or slightly below
* 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.

Where this trial is running

Beijing

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

Conditions Hypoparathyroidism; hypoparathyroidism; PTH; mRNA