PaTHway CHINA TRIAL: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Trial, With an Open-Label Extension, Investigating the Safety, Tolerability and Efficacy of TransCon PTH Administered Subcutaneously Daily in Adults With Hypoparathyroidism
This study is limited to conduct in China only. The primary objective is to assess the treatment effect of daily TransCon PTH on serum calcium (sCa) levels within the normal range and stopping from therapeutic doses of active vitamin D (calcitriol) or active vitamin D analogue (alfacalcidol) and calcium at 26 weeks of treatment. All subjects will start with 18 mcg of study drug and will be individually and progressively titrated to an optimal dose over a 26-week double blind period, followed by an open label extension period up to 156 weeks. TransCon PTH or placebo will be administered as a subcutaneous injection using a pre-filled injection pen. Neither trial participants nor their doctors will know who has been assigned to each group. After the 26 weeks, participants will continue in the trial as part of a long-term extension study. During the extension, all participants will receive TransCon PTH, with the dose adjusted to their individual needs.
• 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 (below the ULN of local laboratory) serum PTH levels.
• Requirement for doses of SoC (e.g., calcitriol, alfacalcidol, calcium supplements) at or above a minimum threshold:
• • 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, and calcium should be stable for at least 5 weeks prior to Screening
• Optimization of supplements prior to randomization to achieve the target serum levels of:
‣ 25(OH) vitamin D levels of 10-100 ng/mL (25-250 nmol/L) and
⁃ Magnesium level in the normal range, or just below the normal range i.e.: ≥1.3 mg/dL (0.53 mmol/L) and
⁃ Albumin-adjusted sCa level in the normal range, or just below the normal range, i.e.: 7.8-10.6 mg/dL (or 1.95-2.64 mmol/L)
• 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 non-dominant 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/L
• 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 SC 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 ICF in accordance with GCP