A Dose Escalation Trial Evaluating Safety, Efficacy, and Pharmacokinetics of TransCon CNP Administered Once Weekly in Prepubertal Children With Achondroplasia

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

The trial is a multicenter, double-blind, randomized, placebo-controlled, dose escalation trial of weekly TransCon CNP administered subcutaneously in prepubertal children 2 to 10 years old, inclusive, with Achondroplasia.

Study Overview

• Status: Completed
• Conditions: Achondroplasia
• Intervention / Treatment: Drug: TransCon CNP; Drug: Placebo for TransCon CNP

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Ascendis Pharma Investigational Site
• Austria
  • Linz, Austria, 4020
    • Ascendis Pharma Investigational Site
• Denmark
  • Copenhagen, Denmark, 2100
    • Ascendis Pharma Investigational Site
• Germany
  • Berlin, Germany, 13353
    • Ascendis Pharma Investigational Site
• Ireland
  • Dublin, Ireland, D01 YC76
    • Ascendis Pharma Investigational Site
• New Zealand
  • Auckland, New Zealand, 1023
    • Ascendis Pharma Investigational Site
• Portugal
  • Coimbra, Portugal, 3000-602
    • Ascendis Pharma Investigational Site
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Ascendis Pharma Investigational Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Ascendis Pharma Investigational Site
  • Minnesota
    • Saint Paul, Minnesota, United States, 55102
      • Ascendis Pharma Investigational Site
  • Missouri
    • Columbia, Missouri, United States, 65212
      • Ascendis Pharma Investigational Site
  • New York
    • Buffalo, New York, United States, 14203
      • Ascendis Pharma Investigational Site
  • Texas
    • Houston, Texas, United States, 77030
      • Ascendis Pharma Investigational Site
  • Washington
    • Seattle, Washington, United States, 98105
      • Ascendis Pharma Investigational Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Ascendis Pharma Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 10 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Clinical diagnosis of ACH with genetic confirmation
2. Age between 2 to 10 years old (inclusive) at Screening Visit
3. Prepubertal (Stage 1 breasts for girls or testicular volume < 4ml for boys) at Screening Visit
4. Able to stand without assistance
5. Caregiver willing and able to administer subcutaneous injections of study drug

Exclusion Criteria:

1. Clinically significant findings at Screening that:

   • are expected to require surgical intervention during participation in the trial or
   • are musculoskeletal in nature, such as Salter-Harris fractures and severe hip pain or
   • otherwise are considered by investigator or Medical Monitor/Medical Expert to make a participant unfit to receive study drug or undergo trial related procedures
2. Have received treatment (>3 months) of human growth hormone (hGH) or other medications known to affect stature or body proportionality at any time
3. Have received any dose of medications intended to affect stature or body proportionality within the previous 6 months of Screening Visit
4. Have received any study drug or device intended to affect stature or body proportionality at any time
5. History or presence of injury or disease of the growth plate(s), other than Achondroplasia, that affects growth potential of long bones

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TransCon CNP 6 mcg; TransCon CNP 6 mcg CNP/kg delivered once weekly by subcutaneous injection.	Drug: TransCon CNP; TransCon CNP drug product is a lyophilized powder in a single-use vial containing either TransCon CNP 3.9 mg CNP-38/vial or TransCon CNP 0.80 mg CNP-38/vial. Prior to use, the lyophilized powder is reconstituted with sterile water for injection and administered by subcutaneous injection via syringe and needle.
Experimental: TransCon CNP 20 mcg; TransCon CNP 20 mcg CNP/kg delivered once weekly by subcutaneous injection.	Drug: TransCon CNP; TransCon CNP drug product is a lyophilized powder in a single-use vial containing either TransCon CNP 3.9 mg CNP-38/vial or TransCon CNP 0.80 mg CNP-38/vial. Prior to use, the lyophilized powder is reconstituted with sterile water for injection and administered by subcutaneous injection via syringe and needle.
Experimental: TransCon CNP 50 mcg; TransCon CNP 50 mcg CNP/kg delivered once weekly by subcutaneous injection.	Drug: TransCon CNP; TransCon CNP drug product is a lyophilized powder in a single-use vial containing either TransCon CNP 3.9 mg CNP-38/vial or TransCon CNP 0.80 mg CNP-38/vial. Prior to use, the lyophilized powder is reconstituted with sterile water for injection and administered by subcutaneous injection via syringe and needle.
Experimental: TransCon CNP 100 mcg; TransCon CNP 100 mcg CNP/kg delivered once weekly by subcutaneous injection.	Drug: TransCon CNP; TransCon CNP drug product is a lyophilized powder in a single-use vial containing either TransCon CNP 3.9 mg CNP-38/vial or TransCon CNP 0.80 mg CNP-38/vial. Prior to use, the lyophilized powder is reconstituted with sterile water for injection and administered by subcutaneous injection via syringe and needle.
Placebo Comparator: Placebo; Placebo mimicking 6, 20, 50, or 100 mcg CNP/kg delivered once weekly by subcutaneous injection.	Drug: Placebo for TransCon CNP; Weekly subcutaneously injection of placebo.
Experimental: Open-Label Extension Period: TransCon CNP; Participants who completed the 52-week blinded treatment period continued into the 104-week open-label extension period and received treatment with TransCon CNP (navepegritide) doses escalated up to a maximum of 100 mcg/kg delivered once weekly by subcutaneous injection.	Drug: TransCon CNP; TransCon CNP drug product is a lyophilized powder in a single-use vial containing either TransCon CNP 3.9 mg CNP-38/vial or TransCon CNP 0.80 mg CNP-38/vial. Prior to use, the lyophilized powder is reconstituted with sterile water for injection and administered by subcutaneous injection via syringe and needle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Height Velocity (cm/Year) After 52 Weeks of Double-blind Treatment	The primary efficacy analysis compared the difference in the primary efficacy endpoint between the TransCon CNP treatment group and the pooled placebo group using an ANCOVA model with the annualized height velocity (AHV) at Week 52 as the response variable, treatment (dose groups and placebo) and sex as factors, baseline age and baseline height SDS as the covariates, and based on the Full Analysis Set.	52 weeks

Collaborators and Investigators

• Sponsor: Ascendis Pharma A/S
• Investigators: Study Director: Aimee D. Shu, MD, Ascendis Pharma, Inc.

Publications and helpful links

General Publications

• Savarirayan R, Hoernschemeyer DG, Ljungberg M, Zarate YA, Bacino CA, Bober MB, Legare JM, Hogler W, Quattrin T, Abuzzahab MJ, Hofman PL, White KK, Ma NS, Schnabel D, Sousa SB, Mao M, Smith A, Chakraborty M, Giwa A, Winding B, Volck B, Shu AD, McDonnell C. Once-weekly TransCon CNP (navepegritide) in children with achondroplasia (ACcomplisH): a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-escalation trial. EClinicalMedicine. 2023 Oct 2;65:102258. doi: 10.1016/j.eclinm.2023.102258. eCollection 2023 Nov.

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2020
• Primary Completion (Actual): September 27, 2022
• Study Completion (Actual): October 1, 2024

Study Registration Dates

• First Submitted: September 9, 2019
• First Submitted That Met QC Criteria: September 9, 2019
• First Posted (Actual): September 11, 2019

Study Record Updates

• Last Update Posted (Actual): May 22, 2025
• Last Update Submitted That Met QC Criteria: May 7, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Achondroplasia; Dwarfism
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Osteochondrodysplasias; Bone Diseases, Developmental; Dwarfism; Achondroplasia
• Other Study ID Numbers: TCC-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No