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

Phase 2

Completed

• Conditions: Achondroplasia
• Interventions: Drug: TransCon CNP; Drug: Placebo for TransCon CNP

• Registration Number: NCT04085523
• Lead Sponsor: Ascendis Pharma A/S

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-09-09
• Study First Submitted QC: 2019-09-09
• Study First Posted: 2019-09-11
• Study Start: 2020-06-24
• Primary Completion: 2022-09-27
• Results First Submitted: 2023-12-27
• Results First Submitted QC: 2024-02-12
• Results First Posted: 2024-03-07
• Study Completion: 2024-10-01
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-07
• Last Update Posted: 2025-05-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 57

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TransCon CNP 6 mcg	TransCon CNP	TransCon CNP 6 mcg CNP/kg delivered once weekly by subcutaneous injection.
Placebo	Placebo for TransCon CNP	Placebo mimicking 6, 20, 50, or 100 mcg CNP/kg delivered once weekly by subcutaneous injection.
TransCon CNP 20 mcg	TransCon CNP	TransCon CNP 20 mcg CNP/kg delivered once weekly by subcutaneous injection.
TransCon CNP 50 mcg	TransCon CNP	TransCon CNP 50 mcg CNP/kg delivered once weekly by subcutaneous injection.
TransCon CNP 100 mcg	TransCon CNP	TransCon CNP 100 mcg CNP/kg delivered once weekly by subcutaneous injection.
Open-Label Extension Period: TransCon CNP	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.

Primary Outcome Measures

Name	Time	Method
Annualized Height Velocity (cm/Year) After 52 Weeks of Double-blind Treatment	52 weeks	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.

Trial Locations

Locations (1)

Ascendis Pharma Investigational Site; 🇵🇹 Coimbra, Portugal