A Trial Investigating the Safety, Tolerability and Efficacy of TransCon PTH Administered Daily in Adults With Hypoparathyroidism

Inclusion Criteria

• Males and females, ≥18 years of age
• Subjects with postsurgical chronic HP, or auto-immune, genetic, or idiopathic HP for at least 26 weeks. Diagnosis of HP is established based on historic hypocalcemia in the setting of inappropriately low serum PTH levels
• Requirement for doses of SoC (e.g., calcitriol, alfacalcidol, calcium supplements) at or above a minimum threshold:
• For countries other than Japan: requirement for a dose of calcitriol ≥0.5 μg/day, or alfacalcidol ≥1.0 μg/day and (elemental) calcium ≥800 mg/day (e.g., calcium citrate, calcium carbonate etc.) for at least 12 weeks prior to Screening. In addition, the dose of calcitriol, or alfacalcidol, or calcium should be stable for at least 5 weeks prior to Screening
• For Japan: requirement for a dose of calcitriol ≥1.0 μg/day, or alfacalcidol ≥2.0 μg/day for at least 12 weeks prior to Screening. In addition, the dose of calcitriol or alfacalcidol should be stable for at least 5 weeks prior to Screening. In Japan only (due to local practice and dietary patterns), there is no requirement to exceed a minimum dose of calcium supplements
• Optimization of supplements prior to randomization to achieve the target serum levels of:
• 25(OH) vitamin D levels of 20-80 ng/mL (49-200 nmol/L) and
• Magnesium level in the normal range, or just below the normal range and
• Albumin-adjusted or ionized sCa level in the normal range, or just below the normal range
• The subject demonstrates a 24-hour uCa excretion of ≥125 mg/24h (on a sample collected within 52 weeks prior to Screening or during the Screening Period)
• BMI 17- 40 kg/m2 at Screening
• If ≤25 years of age, radiological evidence of epiphyseal closure based on X-ray of nondominant wrist and hand
• Thyroid-stimulating hormone (TSH) within normal laboratory limits within the 6 weeks prior to Visit 1; if on suppressive therapy for a history of thyroid cancer, TSH level must be ≥0.2 mIU/mL
• If treated with thyroid hormone replacement therapy, the dose must have been stable for at least 5 weeks prior to Screening
• eGFR ≥30 mL/min/1.73 m2 during Screening
• Able to perform daily subcutaneous self-injections of study drug (or have a designee to perform injections) via a pre-filled injection pen
• Able and willing to provide written and signed informed consent in accordance with GCP

Exclusion Criteria

• Impaired responsiveness to PTH (pseudohypoparathyroidism) 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 HP, 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 basal cell skin cancer); active hyperparathyroidism; parathyroid carcinoma within 5 years prior to Screening; acromegaly; or multiple endocrine neoplasia types 1 and 2
• High risk thyroid cancer within 2 years, requiring suppression of TSH 30 μg/day, or systemic corticosteroids (other than as replacement therapy)
• 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