A Study to Test the Effects and Safety of Palopegteriparatide in Adolescents With Long-term Hypoparathyroidism

A Phase 3, Multicenter, Open-Label Single-Arm Clinical Trial to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of Palopegteriparatide Administered Subcutaneously Daily in the Adolescent Population (12 Years to Less Than 18 Years of Age) With Chronic Hypoparathyroidism

This trial will enroll adolescents between ages of ≥12 and <18 years with clinically diagnosed hypoparathyroidism . The purpose of the study is to see how well treatment with once-daily palopegteriparatide works and how safe it is. At least 12 participants will receive palopegteriparatide for 234 weeks. This trial will be conducted in Europe.

Study Overview

• Status: Recruiting
• Conditions: Hypoparathyroidism
• Intervention / Treatment: Combination product: Palopegteriparatide

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ascendis Registry Inquiries; Phone Number: +45 61242484; Email: asnd_registryinquiries@ascendispharma.com

Study Locations

• Poland
  • Lodz, Poland, 93-338
    • Recruiting
    • Ascendis Pharma Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1. Males and females, 12 to less than 18 years of age
• 2. Participants with postsurgical chronic hypoparathyroidism, or auto-immune, genetic, or idiopathic hypoparathyroidism for at least 26 weeks
• 3. Normal levels of serum 25(OH) vitamin D and magnesium
• 4. Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73
• 5. Able to perform daily subcutaneous self-injections of palopegteriparatide (or have a caregiver to perform injections)
• 6. Body mass index (BMI) Z-score greater than -2 SDS and below + 3 SDS
• 7. Written, signed informed consent

Exclusion Criteria:

• 1. Impaired responsiveness to PTH which is characterized as PTH-resistance, with elevated PTH levels in the setting of hypocalcemia
• 2. Any disease that might affect calcium metabolism or calcium-phosphate homeostasis or PTH levels other than hypoparathyroidism, such as active hyperthyroidism
• 3. 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
• 4. Use of thiazide diuretic
• 5. Use of PTH-like drugs
• 6. 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
• 7. 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
• 8. Non-hypocalcemic seizure disorder with occurrence of a seizure within 26 weeks prior to Screening
• 9. Increased risk for osteosarcoma
• 10. Female participants who are pregnant, intend to become pregnant, or are lactating
• 11. Diagnosed drug or alcohol dependence within 3 years prior to Screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Palopegteriparatide, once daily; Participants will receive palopegteriparatide by subcutaneous injection for 234 weeks	Combination product: Palopegteriparatide; Subcutaneous injection for 234 weeks; Other Names: Yorvipath

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants meeting the multicomponent efficacy endpoint at Week 26	The multi-component endpoint is the percentage of participants who met the following criteria at Week 26: 1) albumin-adjusted serum calcium within the normal range ; 2) independence from active vitamin D, and 3) independence from therapeutic doses of calcium	26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants meeting the multicomponent efficacy endpoint through Week 234	The multi-component endpoint is the percentage of participants who met the following criteria: 1) albumin-adjusted serum calcium within the normal range (8.3-10.6 mg/dL) 2) independence from active vitamin D; and 3) independence from therapeutic doses of calcium.	234 weeks
Serum biochemistries	Change from baseline and normalization of serum calcium, mmol/L	234 weeks
Serum biochemistries	Change from baseline and normalization of serum phosphate, mmol/L	234 weeks
Serum biochemistries	Change from baseline and normalization of serum creatinine, mL/min	234 weeks
Renal calcifications	Incidence of nephrolithiasis or nephrocalcinosis on renal ultrasound	234 weeks
Hospitalizations/emergency room (ER)/urgent care visits	Number of hospitalizations/ER/urgent care visits	234 weeks
Adverse events	Percentage of participants experiencing an adverse event	234 weeks
Bone mineral density	Bone mineral density measured by dual-energy x-ray absorptiometry (DXA)	234 weeks
Bone turnover marker	Qualitative evaluation of bone turnover marker ctx (ng/L) in blood sample	234 weeks
Bone turnover marker	Qualitative evaluation of bone turnover marker p1np (ng/mL) in blood sample	234 weeks
HPES-Symptom score	Hypoparathyroidism Patient Experience Scale (HPES) Symptom score, including Physical and Cognitive Domains	234 weeks
HPES-Impact score	Hypoparathyroidism Patient Experience Scale (HPES) Impact score, including Physical Functioning and Daily Life Domains	234 weeks
Urine biochemistries	Urine biochemistries to include 24-hour urine calcium	234 weeks

Collaborators and Investigators

• Sponsor: Ascendis Pharma A/S
• Investigators: Study Director: Medical Director, MD, Ascendis Pharma A/S

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2031

Study Registration Dates

• First Submitted: June 23, 2026
• First Submitted That Met QC Criteria: July 10, 2026
• First Posted (Actual): July 16, 2026

Study Record Updates

• Last Update Posted (Actual): July 16, 2026
• Last Update Submitted That Met QC Criteria: July 10, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Parathyroid Diseases; Hypoparathyroidism
• Other Study ID Numbers: ASND0035

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No