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

NCT ID: NCT04085523

Last Updated: 2025-05-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-24
• Study Completion Date: 2024-10-01

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.

Conditions

Achondroplasia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

TransCon CNP 6 mcg

TransCon CNP 6 mcg CNP/kg delivered once weekly by subcutaneous injection.

Group Type: EXPERIMENTAL

TransCon CNP

Intervention Type: DRUG

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.

TransCon CNP 20 mcg

TransCon CNP 20 mcg CNP/kg delivered once weekly by subcutaneous injection.

Group Type: EXPERIMENTAL

TransCon CNP

Intervention Type: DRUG

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.

TransCon CNP 50 mcg

TransCon CNP 50 mcg CNP/kg delivered once weekly by subcutaneous injection.

Group Type: EXPERIMENTAL

TransCon CNP

Intervention Type: DRUG

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.

TransCon CNP 100 mcg

TransCon CNP 100 mcg CNP/kg delivered once weekly by subcutaneous injection.

Group Type: EXPERIMENTAL

TransCon CNP

Intervention Type: DRUG

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

Placebo mimicking 6, 20, 50, or 100 mcg CNP/kg delivered once weekly by subcutaneous injection.

Group Type: PLACEBO_COMPARATOR

Placebo for TransCon CNP

Intervention Type: DRUG

Weekly subcutaneously injection of placebo.

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.

Group Type: EXPERIMENTAL

TransCon CNP

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Placebo for TransCon CNP

Weekly subcutaneously injection of placebo.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ascendis Pharma A/S

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Aimee D. Shu, MD

Role: STUDY_DIRECTOR

Ascendis Pharma, Inc.

Locations

Ascendis Pharma Investigational Site

Little Rock, Arkansas, United States

Ascendis Pharma Investigational Site

Aurora, Colorado, United States

Ascendis Pharma Investigational Site

Saint Paul, Minnesota, United States

Ascendis Pharma Investigational Site

Columbia, Missouri, United States

Ascendis Pharma Investigational Site

Buffalo, New York, United States

Ascendis Pharma Investigational Site

Houston, Texas, United States

Ascendis Pharma Investigational Site

Seattle, Washington, United States

Ascendis Pharma Investigational Site

Madison, Wisconsin, United States

Ascendis Pharma Investigational Site

Parkville, Victoria, Australia

Ascendis Pharma Investigational Site

Linz, , Austria

Ascendis Pharma Investigational Site

Copenhagen, , Denmark

Ascendis Pharma Investigational Site

Berlin, , Germany

Ascendis Pharma Investigational Site

Dublin, , Ireland

Ascendis Pharma Investigational Site

Auckland, , New Zealand

Ascendis Pharma Investigational Site

Coimbra, , Portugal

Countries

United States; Australia; Austria; Denmark; Germany; Ireland; New Zealand; Portugal

References

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.

Reference Type: RESULT

PMID: 37823031 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

TCC-201

Identifier Type: -

Identifier Source: org_study_id