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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Achondroplasia

Intervention / Treatment
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* Drug: TransCon CNP
* Drug: Placebo for TransCon CNP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of ACH with genetic confirmation Age between 2 to 10 years old (inclusive) at Screening Visit Prepubertal (Stage 1 breasts for girls or testicular volume < 4ml for boys) at Screening Visit Able to stand without assistance Caregiver willing and able to administer subcutaneous injections of study drug Exclusion Criteria: 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 Have received treatment (>3 months) of human growth hormone (hGH) or other medications known to affect stature or body proportionality at any time Have received any dose of medications intended to affect stature or body proportionality within the previous 6 months of Screening Visit Have received any study drug or device intended to affect stature or body proportionality at any time History or presence of injury or disease of the growth plate(s), other than Achondroplasia, that affects growth potential of long bones

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: There are 5 cohorts enrolling approximately 60 subjects who will be randomized to receive either TransCon CNP or Placebo in a 3:1 ratio
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TransCon CNP 6 mcg<br>TransCon CNP 6 mcg CNP/kg delivered once weekly by subcutaneous injection. | Drug: TransCon CNP<br>* 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.<br>|
| Experimental: TransCon CNP 20 mcg<br>TransCon CNP 20 mcg CNP/kg delivered once weekly by subcutaneous injection. | Drug: TransCon CNP<br>* 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.<br>|
| Experimental: TransCon CNP 50 mcg<br>TransCon CNP 50 mcg CNP/kg delivered once weekly by subcutaneous injection. | Drug: TransCon CNP<br>* 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.<br>|
| Experimental: TransCon CNP 100 mcg<br>TransCon CNP 100 mcg CNP/kg delivered once weekly by subcutaneous injection. | Drug: TransCon CNP<br>* 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.<br>|
| Placebo Comparator: Placebo<br>Placebo mimicking 6, 20, 50, or 100 mcg CNP/kg delivered once weekly by subcutaneous injection. | Drug: Placebo for TransCon CNP<br>* Weekly subcutaneously injection of placebo.<br>|
| Experimental: Open-Label Extension Period<br>Subjects who complete the 52-week blinded treatment period can continue into the 104-week open-label extension period and will receive treatment with TransCon CNP. | Drug: TransCon CNP<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) | Safety and tolerability of once weekly TransCon CNP treatment or placebo | 52 weeks | 
| Annualized height velocity (centimeters/year) at 52 weeks | Annualized height velocity measured in centimeters over 52 weeks for TransCon CNP or placebo | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Achondroplasia, Dwarfism