Once-weekly TransCon CNP (navepegritide) in children with achondroplasia (ACcomplisH): a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-escalation trialResearch in context
In: EClinicalMedicine, Jg. 65 (2023-11-01), Heft 102258-
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Summary: Background: 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. Methods: 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). Findings: 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. Interpretation: 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. Funding: Ascendis Pharma, A/S.
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Once-weekly TransCon CNP (navepegritide) in children with achondroplasia (ACcomplisH): a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-escalation trialResearch in context
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Autor/in / Beteiligte Person: | Savarirayan, Ravi ; Hoernschemeyer, Daniel G. ; Ljungberg, Merete ; Zarate, Yuri A. ; Bacino, Carlos A. ; Bober, Michael B. ; Legare, Janet M. ; Högler, Wolfgang ; Quattrin, Teresa ; M. Jennifer Abuzzahab ; Hofman, Paul L. ; White, Klane K. ; Ma, Nina S. ; Schnabel, Dirk ; Sousa, Sérgio B. ; Mao, Meng ; Smith, Alden ; Chakraborty, Mukta ; Giwa, Adebola ; Winding, Bent ; Volck, Birgitte ; Shu, Aimee D. ; McDonnell, Ciara |
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Zeitschrift: | EClinicalMedicine, Jg. 65 (2023-11-01), Heft 102258- |
Veröffentlichung: | Elsevier, 2023 |
Medientyp: | academicJournal |
ISSN: | 2589-5370 (print) |
DOI: | 10.1016/j.eclinm.2023.102258 |
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