PDF(Pubmed)
Abstract：
UNASSIGNED: TransCon CNP (navepegritide) is an investigational prodrug of C-type natriuretic peptide (CNP) designed to allow for continuous CNP exposure with once-weekly dosing. This 52-week phase 2 (ACcomplisH) trial assessed the safety and efficacy of TransCon CNP in children with achondroplasia.
UNASSIGNED: ACcomplisH is a global, randomised, double-blind, placebo-controlled, dose-escalation trial. Study participants were recruited between June 10, 2020, and September 24, 2021. Eligible participants were prepubertal, aged 2-10 years, with genetically confirmed achondroplasia, and randomised 3:1 to once-weekly subcutaneous injections of TransCon CNP (6, 20, 50, or 100 μg CNP/kg/week) or placebo for 52 weeks. Primary objectives were safety and annualised growth velocity (AGV). ACcomplisH is registered with ClinicalTrials.gov (NCT04085523) and Eudra (CT 2019-002754-22).
UNASSIGNED: Forty-two participants received TransCon CNP at doses of 6 μg (n = 10; 7 female), 20 μg (n = 11; 3 female), 50 μg (n = 10; 3 female), or 100 μg (n = 11; 6 female) CNP/kg/week, with 15 receiving placebo (5 female). Treatment-emergent adverse events (TEAEs) were mild or moderate with no grade 3/4 events reported. There were 2 serious TEAEs that were assessed as not related to TransCon CNP. Eleven injection site reactions occurred in 8 participants receiving TransCon CNP and no symptomatic hypotension occurred. TransCon CNP demonstrated a dose-dependent improvement in AGV. At 52 weeks, TransCon CNP 100 μg CNP/kg/week significantly improved AGV vs placebo (least squares mean [95% CI] 5.42 [4.74-6.11] vs 4.35 [3.75-4.94] cm/year; p = 0.0218), and improved achondroplasia-specific height SDS from baseline (least squares mean [95% CI] 0.22 [0.02-0·41] vs -0·08 [-0.25 to 0.10]; p = 0.0283). All participants completed the randomised period and continued in the ongoing open-label extension period receiving TransCon CNP 100 μg CNP/kg/week.
UNASSIGNED: This phase 2 trial suggests that TransCon CNP is effective, safe, with low injection site reaction frequency, and may provide a novel, once-weekly treatment option for children with achondroplasia. These results support TransCon CNP at 100 μg CNP/kg/week in the ongoing pivotal trial.
UNASSIGNED: Ascendis Pharma, A/S.
UNASSIGNED: ACcomplisH is a global, randomised, double-blind, placebo-controlled, dose-escalation trial. Study participants were recruited between June 10, 2020, and September 24, 2021. Eligible participants were prepubertal, aged 2-10 years, with genetically confirmed achondroplasia, and randomised 3:1 to once-weekly subcutaneous injections of TransCon CNP (6, 20, 50, or 100 μg CNP/kg/week) or placebo for 52 weeks. Primary objectives were safety and annualised growth velocity (AGV). ACcomplisH is registered with ClinicalTrials.gov (NCT04085523) and Eudra (CT 2019-002754-22).
UNASSIGNED: Forty-two participants received TransCon CNP at doses of 6 μg (n = 10; 7 female), 20 μg (n = 11; 3 female), 50 μg (n = 10; 3 female), or 100 μg (n = 11; 6 female) CNP/kg/week, with 15 receiving placebo (5 female). Treatment-emergent adverse events (TEAEs) were mild or moderate with no grade 3/4 events reported. There were 2 serious TEAEs that were assessed as not related to TransCon CNP. Eleven injection site reactions occurred in 8 participants receiving TransCon CNP and no symptomatic hypotension occurred. TransCon CNP demonstrated a dose-dependent improvement in AGV. At 52 weeks, TransCon CNP 100 μg CNP/kg/week significantly improved AGV vs placebo (least squares mean [95% CI] 5.42 [4.74-6.11] vs 4.35 [3.75-4.94] cm/year; p = 0.0218), and improved achondroplasia-specific height SDS from baseline (least squares mean [95% CI] 0.22 [0.02-0·41] vs -0·08 [-0.25 to 0.10]; p = 0.0283). All participants completed the randomised period and continued in the ongoing open-label extension period receiving TransCon CNP 100 μg CNP/kg/week.
UNASSIGNED: This phase 2 trial suggests that TransCon CNP is effective, safe, with low injection site reaction frequency, and may provide a novel, once-weekly treatment option for children with achondroplasia. These results support TransCon CNP at 100 μg CNP/kg/week in the ongoing pivotal trial.
UNASSIGNED: Ascendis Pharma, A/S.
摘要：
■TransConCNP（navepegrititide）是C型利钠肽（CNP）的研究性前药，旨在允许每周一次给药连续CNP暴露。这项为期52周的2期（ACcomplexisH）试验评估了TransConCNP在软骨发育不全儿童中的安全性和有效性。
■犯罪是全球性的，随机化，双盲,安慰剂对照,剂量递增试验。研究参与者在2020年6月10日至2021年9月24日之间招募。符合条件的参与者是青春期前，2-10岁,遗传证实软骨发育不全，随机3：1，每周一次皮下注射TransConCNP（6、20、50或100μgCNP/kg/周）或安慰剂，持续52周。主要目标是安全性和年生长速度(AGV)。ACcompleisH已在ClinicalTrials.gov（NCT04085523）和Eudra（CT2019-002754-22）注册。
■42名参与者接受了6μg剂量的TransConCNP（n=10；7名女性），20μg（n=11；3雌性），50μg（n=10；3雌性），或100μg（n=11；6雌性）CNP/kg/周，15人接受安慰剂（5名女性）。治疗引起的不良事件（TEAE）为轻度或中度，无3/4级事件报告。有2个严重的TEAE被评估为与TransConCNP无关。在接受TransConCNP的8名参与者中发生了11次注射部位反应，没有发生症状性低血压。TransConCNP在AGV中表现出剂量依赖性改善。52周时,TransConCNP100μgCNP/kg/周显着改善了AGV与安慰剂（最小二乘平均值[95％CI]5.42[4.74-6.11]vs4.35[3.75-4.94]cm/年；p=0.0218），与基线相比，软骨发育不全特异性高度SDS有所改善（最小二乘均值[95％CI]0.22[0.02-0·41]vs-0·08[-0.25至0.10]；p=0.0283）。所有参与者都完成了随机周期，并在正在进行的开放标签延长周期中继续接受TransConCNP100μgCNP/kg/周。
■这个2期试验表明TransConCNP是有效的，安全,注射部位反应频率低，并可能提供一部小说，软骨发育不全儿童每周一次的治疗选择。这些结果支持在正在进行的关键试验中以100μgCNP/kg/周的TransConCNP。
■AscendisPharma，A/S.
■犯罪是全球性的，随机化，双盲,安慰剂对照,剂量递增试验。研究参与者在2020年6月10日至2021年9月24日之间招募。符合条件的参与者是青春期前，2-10岁,遗传证实软骨发育不全，随机3：1，每周一次皮下注射TransConCNP（6、20、50或100μgCNP/kg/周）或安慰剂，持续52周。主要目标是安全性和年生长速度(AGV)。ACcompleisH已在ClinicalTrials.gov（NCT04085523）和Eudra（CT2019-002754-22）注册。
■42名参与者接受了6μg剂量的TransConCNP（n=10；7名女性），20μg（n=11；3雌性），50μg（n=10；3雌性），或100μg（n=11；6雌性）CNP/kg/周，15人接受安慰剂（5名女性）。治疗引起的不良事件（TEAE）为轻度或中度，无3/4级事件报告。有2个严重的TEAE被评估为与TransConCNP无关。在接受TransConCNP的8名参与者中发生了11次注射部位反应，没有发生症状性低血压。TransConCNP在AGV中表现出剂量依赖性改善。52周时,TransConCNP100μgCNP/kg/周显着改善了AGV与安慰剂（最小二乘平均值[95％CI]5.42[4.74-6.11]vs4.35[3.75-4.94]cm/年；p=0.0218），与基线相比，软骨发育不全特异性高度SDS有所改善（最小二乘均值[95％CI]0.22[0.02-0·41]vs-0·08[-0.25至0.10]；p=0.0283）。所有参与者都完成了随机周期，并在正在进行的开放标签延长周期中继续接受TransConCNP100μgCNP/kg/周。
■这个2期试验表明TransConCNP是有效的，安全,注射部位反应频率低，并可能提供一部小说，软骨发育不全儿童每周一次的治疗选择。这些结果支持在正在进行的关键试验中以100μgCNP/kg/周的TransConCNP。
■AscendisPharma，A/S.
