A Clinical Trial to Evaluate Efficacy and Safety of TransCon CNP Compared With Placebo in Children With Achondroplasia (ApproaCH)

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

The purpose of this clinical trial was to evaluate efficacy and safety of once weekly subcutaneous (SC) doses of 100 µg TransCon CNP/kg compared to placebo on Annualized Growth Velocity after a 52-week randomized treatment period in children aged 2 to 11 years with genetically confirmed Achondroplasia. The double-blind, placebo-controlled treatment period was followed by an Open Label Extension (OLE) period of a 52-week duration.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • Parkville, Australia, 3052
    • Ascendis Pharma Investigational Site
• Canada
  • Montreal, Canada, H3T 1CS
    • Ascendis Pharma Investigational Site
• Denmark
  • Copenhagen, Denmark, 2100
    • Ascendis Pharma Investigational Site
• Ireland
  • Dublin, Ireland, D01 YC76
    • Ascendis Pharma Investigational Site
• New Zealand
  • Auckland, New Zealand, 1023
    • Ascendis Pharma Investigational Site
• Spain
  • Vitoria-Gasteiz, Spain, 1008
    • Ascendis Pharma Investigational Site
• United States
  • Minnesota
    • Saint Paul, Minnesota, United States, 55102
      • Ascendis Pharma Investigational Site
  • Missouri
    • Columbia, Missouri, United States, 65212
      • Ascendis Pharma Investigational Site
  • Texas
    • Houston, Texas, United States, 77030
      • 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 11 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Written, signed informed consent of the parent(s) or legal guardian(s) of the participant, and as required by the institutional review board/human research ethics committee/independent ethics committee (IRB/HREC/IEC).
• Male or female, between 2 and 11 years of age (inclusive) at the time of Screening.
• Clinical diagnosis of Achondroplasia (ACH) with documented genetic confirmation available.
• Able to stand without assistance.
• Parent(s)/legal guardian(s) willing and able to administer weekly SC injections of Investigational Medicinal Product (IMP) and to follow the protocol.
• At least six months of growth and disease history from ACHieve (TCC-NHS-01) trial or comparable growth and disease history available from medical records (pending confirmation by Medical Monitor).
• Considered eligible based on the medical history, physical examination, and the results of vital signs, ECG and clinical laboratory tests performed during the Screening period

Exclusion Criteria:

• Participation (i.e., signed informed consent) in any interventional clinical trial before within 3 months prior to screening.
• Closed epiphysis.
• Known or suspected hypersensitivity to the IMP or related products (trehalose, tris[hydroxymethyl]aminomethane, succinate, and mPEG).
• Had a growth disorder or medical condition other than ACH that results in short stature or abnormal growth such as severe ACH with developmental delay and acanthosis nigricans (SADDAN), hypochondroplasia, growth hormone deficiency, Turner syndrome, pseudoachondroplasia, inflammatory bowel disease, celiac disease, hypothyroidism, hyperthyroidism, pre-diabetes, or diabetes mellitus.
• Have received any dose of prescription medications and IMP or surgical intervention intended to affect stature, growth, or body proportionality at any time.
• Required, or anticipated to require, chronic (> 4 weeks) or repeated treatment (more than twice/year and >3 weeks/year) with systemic corticosteroids during participation in the trial. Chronic use of high-dose inhaled corticosteroids was not allowed.
• Known history of presence of injury or disease of the growth plate(s), other than ACH, that affects growth potential of long bones.

• Known history of any bone-related surgery affecting growth potential of long bones, such as:

  • Orthopedic reconstructive surgery for bone lengthening (e.g., procedures for leg bowing such as 8-plate are not exclusionary).
  • Cervicomedullary decompression surgery without anticipated need for repeat decompression during the time of the trial are allowed with minimum of 6 months of bone healing.
  • Ventriculoperitoneal (VP) shunt and laminectomy with full recovery are allowed with minimum of 6 months of bone healing.
  • Bone fracture within 6 months prior to screening (within 2 months for fracture of digits and buckle fractures).

• Clinically significant findings at Screening, such as:

  • Expected to require surgical intervention during participation in the trial. Common surgeries, such as insertion of grommets, adenoidectomy, tonsillectomy, or myringotomy tube placement, are permitted.
  • Severe untreated sleep apnea or newly initiated sleep apnea treatment (e.g., Continuous Positive Airway Pressure [CPAP] in the previous 2 months prior to Screening).
  • Musculoskeletal disease, such as Salter-Harris fractures or clinical and/or radiographic evidence of severe hip pathology, or
  • Otherwise, are considered by the Investigator and Medical Monitor to make a participant unfit to receive trial treatment or undergo trial related procedures.
• Had evidence at Screening that were consistent with severe cervicomedullary junction compression based on clinical and/or radiologic findings that indicated immediate surgical intervention was required.

• Had a clinically significant finding or arrhythmia as determined by the investigator in consultation with the medical monitor that indicates abnormal cardiac function or conduction that includes, but was not exclusive to:

  • Repaired or unrepaired coarctation.
  • Moderate or greater complexity congenital heart disease including tetralogy of Fallot, Atrioventricular septal defects, truncus arteriosus, total anomalous pulmonary venous return, double outlet right ventricle, or single ventricle heart disease.
• QTcF ≥ 450 msec at the Screening Visit.
• Known history or presence of condition that impacts hemodynamic stability (such as autonomic dysfunction and orthostatic intolerance).

• Known history or presence of the following:

  • Chronic anemia (iron deficiency anemia that is resolved or adequately treated in the Investigator's opinion was allowed).
  • Chronic renal insufficiency (GFR <60 mL/min/1.73 m2 for >3 months).
  • Chronic or recurrent illness that can affect hydration or volume status, including conditions associated with decreased nutritional intake or increased volume loss.
• Known history or presence of malignant disease.
• Participant with serum 25-hydroxy-vitamin D (25OHD) levels of <30 nmol/L (<12 ng/mL) at Screening Visit were excluded. Participants with 25OHD levels between 30-50 nmol/L (12-20 ng/mL) were randomized provided treatment with Vitamin D supplementation was initiated.
• Any disease or condition that, in the opinion of the Investigator, may make the participant unlikely to fully complete the trial, may confound interpretation of trial results, or may present undue risk from receiving trial treatment. This included family situations, complications or manifestations, or medications that might impact safety or be considered confounding.
• Sexually active male and female participants and female partners of male participants of childbearing potential not using a highly effective form of contraceptive for the entire trial period and for 90 days after last dose of trial treatment.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Navepegritide; Participants received Navepegritide (TransCon CNP) 100 micrograms per kilogram (µg/kg) delivered once weekly by subcutaneous injection for a treatment period of up to 52 weeks.	Drug: Navepegritide (TransCon CNP); Once-weekly subcutaneous injection of 100 µg/kg Navepegritide (TransCon CNP)
Placebo Comparator: Placebo for Navepegritide; Participants received placebo matched for Navepegritide (TransCon CNP) 100 µg/kg delivered once weekly by subcutaneous injection for a treatment period of up to 52 weeks.	Drug: Placebo for Navepegritide (TransCon CNP); Once-weekly subcutaneous injection of 100 µg/kg placebo for Navepegritide (TransCon CNP)
Experimental: Open-Label Extension Period: Navepegritide; Participants who completed the 52-week treatment period continued into the open-label extension period and received treatment with navepegritide (TransCon CNP) doses up to Week 104. All participants received navepegritide at a dose of 100 μg/kg/week.	Drug: Navepegritide (TransCon CNP); Once-weekly subcutaneous injection of 100 µg/kg Navepegritide (TransCon CNP)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Growth Velocity (AGV) at Week 52	Annualized growth velocity is defined as (height - baseline height)/(date of height assessment - date of baseline) * 365.25. Annualized growth velocity reported in terms of centimeters (cm) per year. Missing values at Week 52 were imputed by a multiple imputation method.	At Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Height Z-score (ACH-specific) at Week 52	ACH specific Z-scores of height provide a measure of growth relative to other individuals with ACH from the CLARITY database. A height Z-score is a standardized height measure after considering important factors like age and gender. Z-scores (or standard deviation scores) describe how far the measurement deviates from the mean. A height Z-score of 0 indicates that height is equal to the mean in the reference population. Negative numbers indicate values below the mean and positive numbers indicate values above the mean.	Baseline, Week 52
Change From Baseline in Height Z-score (CDC-Based) at Week 52	Z-scores of height are determined using Centers for Disease Control and Prevention (CDC) clinical growth charts for children. A height Z-score is a standardized height measure after considering important factors like age and gender. Z-scores (or standard deviation scores) describe how far the measurement deviates from the median. A height Z-score of 0 indicates that height is equal to the median in the reference population. Negative numbers indicate values below the median and positive numbers indicate values above the median.	Baseline, Week 52

Collaborators and Investigators

• Sponsor: Ascendis Pharma Growth Disorders A/S
• Investigators: Study Director: Medical Director, MD, Ascendis Pharma A/S

Publications and helpful links

General Publications

• McDonnell CM, Irving M, Nolting LA, Abdelrahman SG, Dalby LW, Ikle JM, Jensen SM, Komirenko AS, Ominsky MS, Shu AD, Hove HB. Navepegritide combined with lonapegsomatropin for the treatment of children with achondroplasia: 52-week results from the phase 2 COACH trial. Eur J Endocrinol. 2026 Jun 1;194(6):745-755. doi: 10.1093/ejendo/lvag082.
• Savarirayan R, McDonnell C, Bacino CA, Hoernschemeyer DG, Legare JM, Abuzzahab MJ, Hofman PL, Campeau PM, de Bergua Domingo JM, Ward LM, Smit K, Smith A, Mao M, Ominsky MS, Freiberg LC, Shu AD, Hove HB. Once-Weekly Navepegritide in Children With Achondroplasia: The APPROACH Randomized Clinical Trial. JAMA Pediatr. 2026 Jan 1;180(1):18-25. doi: 10.1001/jamapediatrics.2025.4771.

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2023
• Primary Completion (Actual): August 9, 2024
• Study Completion (Actual): August 13, 2025

Study Registration Dates

• First Submitted: October 25, 2022
• First Submitted That Met QC Criteria: October 25, 2022
• First Posted (Actual): October 28, 2022

Study Record Updates

• Last Update Posted (Actual): July 14, 2026
• Last Update Submitted That Met QC Criteria: June 16, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Osteochondrodysplasias; Bone Diseases, Developmental; Dwarfism; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Achondroplasia
• Other Study ID Numbers: ASND0036

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Not planned

Drug and device information, study documents

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