Phase 3 Study to Evaluate the Safety and Efficacy of Palopegteriparatide in Adolescents with Chronic Hypoparathyroidism
- Trial ID
- 2025-523928-52-00
- Protocol
- ASND0035
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to evaluate the efficacy of palopegteriparatide in adolescents aged 12 to less than 18 years with chronic hypoparathyroidism. This investigation also assesses safety, tolerability, pharmacokinetics, and pharmacodynamics of the subcutaneous administration of the study drug.
Participants
This clinical trial involves a total of 10 participants. The study population consists of male and female adolescents, aged 12 to less than 18 years, diagnosed with chronic hypoparathyroidism. Eligible participants include those with postsurgical, autoimmune, genetic, or idiopathic forms of the condition persisting for at least 26 weeks. Diagnosis is established by a history of hypocalcemia in the presence of inappropriately low parathyroid hormone levels. Key requirements for inclusion include normal levels of serum 25(OH) vitamin D and magnesium prior to randomization, an estimated glomerular filtration rate of ≥30 mL/min/1.73 m2, and a body mass index Z-score between -2 and +3 SDS.
Plans and Procedures
This Phase 3, multicenter, open-label, single-arm clinical trial is designed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of palopegteriparatide administered via subcutaneous injection in adolescents aged 12 to less than 18 years with chronic hypoparathyroidism. The study methodology aims to assess the proportion of participants achieving albumin-adjusted serum calcium within the normal range and achieving independence from active vitamin D and therapeutic doses of calcium by week 26. The research involves a screening visit to confirm eligibility based on criteria such as diagnosis history, magnesium and 25(OH) vitamin D levels, estimated glomerular filtration rate, and body mass index Z-score. Following screening, participants will undergo treatment and follow-up to monitor clinical endpoints. The overall study duration is estimated to conclude by August 2031.
Treatment
The experimental treatment consists of palopegteriparatide, which is provided as a solution for injection in a pre-filled pen. This medication is administered via subcutaneous route on a daily basis.
The available formulations for administration include Yorvipath 168 micrograms/0.56 mL, Yorvipath 294 micrograms/0.98 mL, and Yorvipath 420 micrograms/1.4 mL. This clinical trial is designed to assess the safety, tolerability, pharmacokinetics, and efficacy of these doses in adolescents with hypoparathyroidism.
Efficacy
The efficacy of palopegteriparatide in adolescents with chronic hypoparathyroidism will be evaluated using specific primary endpoints at Week 26. The assessment includes the proportion of participants achieving albumin-adjusted serum calcium levels within the normal range, as measured during the four weeks prior to and on the Week 26 visit.
Additional efficacy criteria at Week 26 involve assessing independence from active vitamin D and therapeutic doses of calcium. For the purpose of this study, calcium intake of ≤600 mg/day via tablets, powder, liquid suspension, or transdermal patch is classified as supplemental rather than therapeutic.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Males and females, 12 to less than 18 years of age at the time of screening (defined as the date of signing informed consent).
- Participants with postsurgical chronic hypoparathyroidism, or auto-immune, genetic, or idiopathic hypoparathyroidism for at least 26 weeks. Diagnosis of hypoparathyroidism is established based on historic hypocalcemia in the setting of inappropriately low serum PTH levels (Hypocalcemia is defined as a value below the reference range for normal at the performing laboratory. Inappropriately low serum PTH levels are defined as at or below the median value of the reference range for normal at the performing laboratory while the concomitant serum calcium is low. If specific lab results at the time of original diagnosis are not available, as historical diagnosis affirming these two components is adequate for inclusion).
- Prior to randomization, achieve normal levels of serum 25(OH) vitamin D and magnesium.
- Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 prior to randomization utilizing the 2009 Schwartz equation: eGFR (mL/min/1.73m^2)= 36.5*((Height (cm))/(Serum Creatinine (µmol/L)))
- Body mass index (BMI) Z-score greater than -2 SDS and below + 3 SDS at Screening.
- Written, signed informed consent provided by parent(s) or legally acceptable representative(s) of the participant, and by the participant if in accordance to local health authority/ethics requirements. Assent from participant obtained in accordance with applicable regulatory requirements.
- Written, signed informed consent provided by parent(s) or legally acceptable representative(s) of the participant, and by the participant if in accordance to local health authority/ethics requirements. Assent from participant obtained in accordance with applicable regulatory requirements.
Exclusion Criteria
- Impaired responsiveness to PTH which is characterized as PTH-resistance, with elevated PTH levels in the setting of hypocalcemia.
- Any disease that might affect calcium metabolism or calcium-phosphate homeostasis or PTH levels other than hypoparathyroidism, such as active hyperthyroidism; Paget disease of bone; severe hypomagnesemia; type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus (HbA1C >9%, documented HbA1C result drawn within 12 weeks prior to Screening is acceptable); severe and chronic liver, or renal disease; Cushing syndrome; multiple myeloma; active pancreatitis; malnutrition; rickets; recent prolonged immobility; active malignancy (other than low-risk well differentiated thyroid cancer or non-melanoma skin cancer); active hyperparathyroidism; parathyroid carcinoma within 5 years prior to Screening; acromegaly; or multiple endocrine neoplasia types 1 and 2.
- Use of loop diuretics, phosphate binders (other than calcium supplements), digoxin, lithium, methotrexate, biotin >30 µg/day, or systemic corticosteroids (other than as replacement therapy). Short course use of steroids (≤2 weeks/year) equivalent to prednisone ≤60 mg/day is permitted.
- Use of thiazide diuretic within 4 weeks prior to the 24-hour urine collection scheduled to occur within 1 week prior to Visit 1.
- Use of PTH-like drugs (whether commercially available or through participation in an investigational 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.
- Use of other drugs known to influence calcium and bone metabolism, such as calcitonin, fluoride tablets (>0.5 mg/day), strontium, or cinacalcet hydrochloride, within 12 weeks prior to Screening.
- Use of osteoporosis therapies known to influence calcium and bone metabolism, i.e., bisphosphonate (oral or intravenous [IV]), denosumab, raloxifene, or romosozumab therapies within 2 years prior to Screening.
- Non-hypocalcemic seizure disorder with occurrence of a seizure within 26 weeks prior to Screening.Note: History of seizures that occur in the setting of hypocalcemia is not exclusionary.
- Increased risk for osteosarcoma, such as those with Paget's disease of bone or unexplained elevations of alkaline phosphatase, hereditary disorders predisposing to osteosarcoma, or with a prior history of substantial external beam or implant radiation therapy involving the skeleton.
- Female participants who are pregnant, intend to become pregnant, or are lactating. Note: Acceptable, effective contraception is required for sexually active women of childbearing potential during the trial and for 2 weeks after the last dose of investigational product.
- Diagnosed drug or alcohol dependence within 3 years prior to Screening.
- Symptomatic or severe cardiac disease within 26 weeks prior to Screening including but not limited to congestive heart failure, symptomatic or severe valvular disease, myocardial infarction, severe or uncontrolled arrhythmias, bradycardia, symptomatic hypotension, abnormal systolic BP, or poorly controlled hypertension based on age and sex-specific reference ranges.
- Cerebrovascular accident within 5 years prior to Screening.
- Within 26 weeks prior to Screening: acute colic due to nephrolithiasis or acute gout. Note: Participants with asymptomatic renal stones are permitted.
- Participation in any other interventional trial in which receipt of investigational product or device occurred within 8 weeks (or within 5.5 times the half-life of the investigational product) (whichever comes first) prior to Screening.
- Known allergy or sensitivity to PTH or any of the excipients [metacresol, mannitol, succinic acid, NaOH/(HCl)] of the investigational product.
- Any other reason that in the opinion of the investigator would prevent the participant from completing participation or following the trial schedule.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Recruiting | 31 Mar 2026 | 3 |
 Germany | Not Yet Recruiting | 31 Mar 2026 | 3 |
 Poland | Recruiting | 31 Mar 2026 | 3 |
 Romania | Not Yet Recruiting | 31 Mar 2026 | 2 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Yorvipath 420 micrograms/1.4 mL solution for injection in pre‑filled pen | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS USE | — | — | PRD10961907 |
Yorvipath 168 micrograms/0.56 mL solution for injection in pre-filled pen | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS USE | — | — | PRD10961898 |
Yorvipath 294 micrograms/0.98 mL solution for injection in pre‑filled pen | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS USE | — | — | PRD10961935 |