Evidence map›Paper›PMID 37823031›Full record

ArticleEClinicalMedicine2023

Once-weekly TransCon CNP (navepegritide) in children with achondroplasia (ACcomplisH): a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-escalation trial.

Ravi Savarirayan, Daniel G Hoernschemeyer, Merete Ljungberg, Yuri A Zarate, Carlos A Bacino, Michael B Bober, Janet M Legare, Wolfgang Högler, Teresa Quattrin, M Jennifer Abuzzahab and 13 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EClinicalMedicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04085523 (ACcomplisH), which is not on this map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
4.9field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04085523 phase2completednot on this map

ACcomplisH: A Phase 2, Multicenter, Double-blind, Randomized, Placebo-controlled, Dose Escalation Trial Evaluating Safety, Efficacy, and Pharmacokinetics of Subcutaneous Doses of TransCon CNP Administered Once Weekly for 52 Weeks in Prepubertal Children With Achondroplasia Followed by an Open-Label Extension Period

TypeinterventionalSponsorAscendis Pharma A/SRan2020 to 2024Enrolled57ConditionsAchondroplasiaArmsTransCon CNP, Placebo for TransCon CNP
3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 19 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
  4. Review
  5. Review
  6. C-Type Natriuretic Peptide Derivatives: Orthopaedic Implications in Achondroplasia.Journal of the Pediatric Orthopaedic Society of North America · 2026
    Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Current understanding and perspectives on growth and long-acting GH therapy in Japan.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors at 13 institutions in 7 countries.

Ravi SavarirayanMurdoch Children's Research Institute, Parkville, Australia.
Daniel G HoernschemeyerUniversity of Missouri Children's Hospital, Columbia, MO, USA.
Merete LjungbergCopenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Yuri A ZarateUniversity of Arkansas for Medical Sciences, Little Rock, AR, USA.
Carlos A BacinoBaylor College of Medicine, Houston, TX, USA.
Michael B BoberNemours Children's Hospital, Wilmington, DE, USA.
Janet M LegareUniversity of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Wolfgang HöglerJohannes Kepler University Linz, Linz, Austria.
Teresa QuattrinUniversity at Buffalo, Buffalo, NY, USA.
M Jennifer AbuzzahabChildren's Minnesota, Minneapolis, MN, USA.
Paul L HofmanThe Liggins Institute, University of Auckland, Auckland, New Zealand.
Klane K WhiteChildren's Hospital Colorado, Aurora, CO, USA.
Nina S MaChildren's Hospital Colorado, Aurora, CO, USA.
Dirk SchnabelCenter for Chronically Sick Children, Charité - University Medicine Berlin, Berlin, Germany.
Sérgio B SousaHospital Pediátrico de Coimbra, Coimbra, Portugal.
Meng MaoAscendis Pharma Inc., Palo Alto, CA, USA.
Alden SmithAscendis Pharma Inc., Palo Alto, CA, USA.
Mukta ChakrabortyAscendis Pharma Inc., Palo Alto, CA, USA.
Adebola GiwaAscendis Pharma Inc., Palo Alto, CA, USA.
Bent WindingAscendis Pharma A/S, Hellerup, Denmark.
Birgitte VolckAscendis Pharma A/S, Hellerup, Denmark.
Aimee D ShuAscendis Pharma Inc., Palo Alto, CA, USA.
Ciara McDonnellChildren's Health Ireland at Temple Street, Dublin, Ireland.
Children's Hospital Colorado · USBaylor College of Medicine · USCharité - Universitätsmedizin Berlin · DECopenhagen University Hospital · DKJohannes Kepler University of Linz · ATMinnesota West Community & Technical College · USRoyal Children's Hospital · AUTrinity College Dublin · IEUniversity at Buffalo, State University of New York · USUniversity of Auckland · NZUniversity of Kentucky · USUniversity of Missouri · USUniversity of Wisconsin–Madison · US

Funding

University of Buffalo Clinical and Translational Science Institute - Supplement SchulyerUL1TR001412 · NCATS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI MURPHY, TIMOTHY F · 2015 to 2024
$33.8M
NCATS NIH HHS UL1 TR001412
6 · The paper itself

Abstract

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.

Indexed as

AchondroplasiaC-type natriuretic peptideGrowthPaediatricTransCon CNP

Identifiers

PMID37823031
PMCPMC10562841
OpenAlexW4387276389

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.