Abstract

Context

Hypoparathyroidism is characterized by insufficient levels of parathyroid hormone (PTH). TransCon PTH is an investigational long-acting prodrug of PTH(1-34) for the treatment of hypoparathyroidism.

Objective

Investigate the safety, tolerability, and efficacy of daily TransCon PTH in adults with hypoparathyroidism.

Design

Phase 2, randomized, double-blind, placebo-controlled 4-week trial with open-label extension.

Patients

Enrolled 59 subjects with hypoparathyroidism.

Interventions

TransCon PTH 15, 18, or 21 µg PTH(1-34)/day or placebo for 4 weeks, followed by a 26-week extension where TransCon PTH dose was titrated (6–60 µg PTH[1-34]/day).

Results

By Week 26, 91% of subjects treated with TransCon PTH achieved independence from standard of care (SoC, defined as active vitamin D = 0 mcg/day and calcium (Ca) ≤ 500 mg/day). Mean 24-hour urine Ca (uCa) decreased from a baseline mean of 415 mg/24h to 178 mg/24h by Week 26 (n=44) while normal serum Ca (sCa) was maintained and serum phosphate (sP) and Ca x P fell within the normal range. By Week 26, mean scores on SF-36 domains increased from below normal at baseline to within the normal range. The Hypoparathyroidism Patient Experience Scale Symptom and Impact scores improved through 26 weeks. TransCon PTH was well-tolerated with no treatment-related serious or severe adverse events.

Conclusions

TransCon PTH enabled independence from oral active vitamin D and reduced Ca supplements (≤ 500 mg/day) for most subjects, achieving normal sCa, sP, uCa, CaxP, and demonstrating improved health-related quality of life. These results support TransCon PTH as a potential hormone replacement therapy for adults with hypoparathyroidism.

中文翻译：

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PaTH Forward：一项 TransCon PTH 治疗成人甲状旁腺功能减退症的随机、双盲、安慰剂对照 2 期试验

摘要

语境

甲状旁腺功能减退症的特征是甲状旁腺激素 (PTH) 水平不足。TransCon PTH 是一种研究性长效 PTH(1-34) 前药，用于治疗甲状旁腺功能减退症。

客观的

研究每日 TransCon PTH 在成人甲状旁腺功能减退症中的安全性、耐受性和有效性。

设计

2 期，随机、双盲、安慰剂对照的 4 周试验，具有开放标签扩展。

耐心

招募了 59 名甲状旁腺功能减退症受试者。

干预

TransCon PTH 15、18 或 21 µg PTH(1-34)/天或安慰剂持续 4 周，然后延长 26 周，其中 TransCon PTH 剂量滴定（6–60 µg PTH[1-34]/天） .

结果

到第 26 周，91% 的接受 TransCon PTH 治疗的受试者实现了独立于标准护理（SoC，定义为活性维生素 D = 0 mcg/天和钙 (Ca) ≤ 500 mg/天）。到第 26 周（n=44），平均 24 小时尿 Ca (uCa) 从基线平均值 415 mg/24h 降至 178 mg/24h，同时维持正常血清 Ca (sCa) 和血清磷酸盐 (sP) 和 Ca x P在正常范围内。到第 26 周，SF-36 域的平均分数从基线低于正常值增加到正常范围内。甲状旁腺功能减退症患者体验量表症状和影响评分在 26 周内有所改善。TransCon PTH 耐受性良好，没有与治疗相关的严重或严重不良事件。

结论

TransCon PTH 使大多数受试者能够独立于口服活性维生素 D 并减少 Ca 补充剂（≤ 500 毫克/天），实现正常的 sCa、sP、uCa、CaxP，并证明与健康相关的生活质量有所改善。这些结果支持 TransCon PTH 作为成人甲状旁腺功能减退症的潜在激素替代疗法。