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HypoparathyroidismPhase 1/2NCT07530705

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

A Phase 1/2 study testing Single subcutaneous injection and Multiple subcutaneous injection in people with Hypoparathyroidism, run by Peking Union Medical College Hospital at 1 site in China.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Hypoparathyroidism
What is being tested?
Single subcutaneous injection and Multiple subcutaneous injection
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteChina
Study dates
17 Nov 2025to 30 Aug 2027
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • At screening, conventional therapy may be optimized to achieve: serum 25-hydroxyvitamin D [25(OH)D] 10-100 ng/mL; serum magnesium and albumin-corrected serum calcium within or slightly below the normal range.

Who cannot join

  • 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.
Show all 13Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Peking Union Medical College Hospital

    Beijing, Beijing Municipality, 100730

Other trials in China

About this study

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

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.

Being tested
Single subcutaneous injection, Multiple subcutaneous injection
Keywords
hypoparathyroidism, XH-02, mRNA
Medical subject headings
Hypoparathyroidism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Single subcutaneous injectionDrug

    Participants will receive a single dose of XH-02 through subcutaneous injection.

  • Multiple subcutaneous injectionDrug

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

Study groups in NCT07530705
Study groupRoleWhat they receive
Single dose (40 μg)ExperimentalParticipants will receive a single subcutaneous dose of 40 μg of XH-02
Receives: Drug: Single subcutaneous injection
Single dose (80 μg)ExperimentalParticipants will receive a single subcutaneous dose of 80 μg of XH-02
Receives: Drug: Single subcutaneous injection
Single dose (120 μg)ExperimentalParticipants will receive a single subcutaneous dose of 120 μg of XH-02
Receives: Drug: Single subcutaneous injection
Multiple doses (20 µg）ExperimentalParticipants will receive a daily subcutaneous injection of 20 µg of XH-02 for 5 consecutive days
Receives: Drug: Multiple subcutaneous injection
Multiple doses (40 µg）ExperimentalParticipants will receive a daily subcutaneous injection of 40 µg of XH-02 for 5 consecutive days
Receives: Drug: Multiple subcutaneous injection
Multiple doses (60 µg）ExperimentalParticipants will receive a daily subcutaneous injection of 60 µg of XH-02 for 5 consecutive days
Receives: Drug: Multiple subcutaneous injection
Multiple doses (80 µg）ExperimentalParticipants will receive a daily subcutaneous injection of 80 µg of XH-02 for 5 consecutive days
Receives: Drug: Multiple subcutaneous injection

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: 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)

  1. PTH(1-84) (efficacy)

    serum PTH(1-84)

    Measured: 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.

  2. PTH (efficacy)

    serum PTH

    Measured: 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

  3. Serum calcium (efficacy)

    Serum calcium

    Measured: 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

  4. Serum phosphorus (efficacy)

    Serum phosphorus

    Measured: 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

  5. Serum magnesium (efficacy)

    Serum magnesium

    Measured: 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

  6. 1, 25-Dihydroxyvitamin D3 (efficacy)

    Serum 1, 25-Dihydroxyvitamin D3

    Measured: Single dose: Predose (within one hour before administration); and 24, 48, and 72 hours postdose. Multiple dose: Predose on Day 1, Day 3, Day 5; and 48 hours and 72 hours after the last dose.

  7. 24-hour urine calcium (efficacy)

    24-hour urine calcium (24hUCa)

    Measured: Single dose: Predose (within 3 days before administration), and 24, 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

  8. Fractional Excretion of calcium (efficacy)

    Fractional Excretion of calcium (FECa)

    Measured: Single dose: Predose (within one hour before administration), and 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Apr 2026
  2. Study start17 Nov 2025
  3. Primary completion30 May 2027 (estimated)
  4. Study completion30 Aug 2027 (estimated)

Why it stopped: Enrollment temporarily suspended in accordance with a newly implemented regulation, State Council Decree No. 818, on clinical research and clinical translation of new biomedical technologies; pending review and approval.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
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.
Masking
None (open label)
Enrolment
15 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07530705
Sponsor's protocol ID
K9040
Status last verified
Apr 2026
First submitted
1 Apr 2026
Last updated
25 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: The investigators do not plan to share Individual Participant Data (IPD) due to confidentiality agreements and participant privacy commitments.

Publications

  • 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.

    PubMed 34035281

  • 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.

    PubMed 35974422

  • 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.

    PubMed 32738041

  • 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.

    PubMed 30540559

  • 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.

    PubMed 36271471

  • 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.

    PubMed 32212275

  • 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.

    PubMed 36389126

  • 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.

    PubMed 33687651

  • 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.

    PubMed 33599907

  • 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.

    PubMed 36054621

  • 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.

    PubMed 26943721

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Single subcutaneous injection and Multiple subcutaneous injection in people with Hypoparathyroidism, run by Peking Union Medical College Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: paused, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse events (safety) (time frame: 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07530705, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2026.

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