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.

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