TransCon CNP for Achondroplasia

(ApproaCH Trial)

Recruiting at 9 trial locations

Overseen By Vibeke Breinholt

Age: < 18

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Ascendis Pharma Growth Disorders A/S

Must not be taking: Systemic corticosteroids

Disqualifiers: Growth disorders, Diabetes, Heart disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

84 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if regular injections can help children with Achondroplasia grow taller by making their bones grow faster. Vosoritide has shown promising results in increasing growth in children with achondroplasia.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on medications or treatments that affect growth or body proportionality, you may not be eligible to participate.

Is TransCon CNP safe for humans?

TransCon CNP has been tested in clinical trials and was generally well tolerated, with no serious side effects reported. It was designed to provide a steady release of the active ingredient, which helps avoid high levels that could cause heart-related side effects. ^{1 2 3 4 5}

How is the drug TransCon CNP different from other treatments for achondroplasia?

TransCon CNP is unique because it is a long-acting prodrug that releases C-type natriuretic peptide (CNP) slowly over time, allowing for once-weekly dosing. This sustained release provides continuous exposure to CNP, which can improve bone growth more effectively and with fewer cardiovascular side effects compared to daily treatments like vosoritide. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for children aged 2 to 11 with confirmed Achondroplasia who can stand without assistance. They must have a history of growth and disease from previous trials or medical records, and their parents must consent and be able to administer weekly injections. Children with chronic anemia, renal insufficiency, recent participation in other clinical trials, closed epiphysis, hypersensitivity to the drug components, other growth disorders or conditions affecting stature are excluded.

Inclusion Criteria

I can stand up on my own without help.

My guardian can give me weekly shots and follow the study rules.

My recent health checks and tests show I am fit for the trial.

Exclusion Criteria

I need urgent surgery due to severe neck spine compression.

Have a clinically significant finding or arrhythmia as determined by the investigator in consultation with the medical monitor that indicates abnormal cardiac function or conduction

I have had surgery on my bones that could affect their growth.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive once weekly SC doses of 100 µg CNP/kg or placebo for 52 weeks

52 weeks

Once weekly visits (in-person)

Open-label extension

Participants continue to receive the study drug in an open-label manner for an additional 52 weeks

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo for TransCon CNP
• TransCon CNP

Trial Overview The trial tests TransCon CNP's effectiveness on improving annual growth velocity compared to placebo over one year in children with Achondroplasia. It's a double-blind study where neither participants nor researchers know who receives the real treatment until after the results are collected. Afterward, there's an open-label extension for another year.

Participant Groups

Group I: TransCon CNP Experimental Treatment 1 Intervention

Once weekly double-blinded treatment with SC injection of 100 µg/kg of TransCon CNP for 52 weeks

Group II: Placebo for TransCon CNP Placebo Group 1 Intervention

Once weekly double-blinded treatment with SC injection of 100 µg/kg of Placebo for TransCon CNP for 52 weeks

Who Is Running the Clinical Trial?

Ascendis Pharma Growth Disorders A/S

Lead Sponsor

Trials

4

Recruited

320+

Findings from Research

TransCon CNP (navepegritide) is a promising once-weekly treatment for children with achondroplasia, showing a significant improvement in annualized growth velocity (AGV) compared to placebo after 52 weeks, particularly at the highest dose of 100 μg/kg/week.

The treatment was found to be safe, with mostly mild to moderate side effects and no serious adverse events related to the drug, indicating a favorable safety profile for this new therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-weekly TransCon CNP (navepegritide) in children with achondroplasia (ACcomplisH): a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-escalation trial. Savarirayan, R., Hoernschemeyer, DG., Ljungberg, M., et al.[2023]

TransCon CNP, a novel prodrug for achondroplasia, was found to be well-tolerated in a phase 1 trial with 45 healthy adult males, showing no serious adverse events and no clinically relevant cardiac effects.

The treatment provided sustained release of C-type natriuretic peptide (CNP) for at least 7 days, significantly increasing levels of cGMP, indicating effective engagement with the target receptor, which supports its potential for once-weekly therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 safety, tolerability, pharmacokinetics and pharmacodynamics results of a long-acting C-type natriuretic peptide prodrug, TransCon CNP. Breinholt, VM., Mygind, PH., Christoffersen, ED., et al.[2022]

TransCon CNP, a sustained-release formulation of C-type natriuretic peptide, has shown to be more effective in stimulating bone growth compared to intermittent CNP exposure in preclinical studies with mice and cynomolgus monkeys.

The drug was well tolerated with no adverse cardiovascular effects at therapeutic levels, and it provides prolonged systemic exposure to CNP-38 for at least 7 days, which may enhance its efficacy while minimizing the risk of hypotension associated with short-acting CNP formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TransCon CNP, a Sustained-Release C-Type Natriuretic Peptide Prodrug, a Potentially Safe and Efficacious New Therapeutic Modality for the Treatment of Comorbidities Associated with Fibroblast Growth Factor Receptor 3-Related Skeletal Dysplasias. Breinholt, VM., Rasmussen, CE., Mygind, PH., et al.[2019]

C-type natriuretic peptide (CNP) significantly stimulates endochondral bone growth, as demonstrated in studies using transgenic and knockout mice.

Targeted overexpression or systemic administration of CNP has been shown to reverse impaired skeletal growth in mouse models of achondroplasia, suggesting potential therapeutic applications for this condition in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Genetic basis for skeletal disease. CNP therapy for achondroplasia]. Yasoda, A., Nakao, K.[2010]

References

1. England pubmed.ncbi.nlm.nih.gov

Once-weekly TransCon CNP (navepegritide) in children with achondroplasia (ACcomplisH): a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-escalation trial. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Phase 1 safety, tolerability, pharmacokinetics and pharmacodynamics results of a long-acting C-type natriuretic peptide prodrug, TransCon CNP. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

TransCon CNP, a Sustained-Release C-Type Natriuretic Peptide Prodrug, a Potentially Safe and Efficacious New Therapeutic Modality for the Treatment of Comorbidities Associated with Fibroblast Growth Factor Receptor 3-Related Skeletal Dysplasias. [2019]

4. Japan pubmed.ncbi.nlm.nih.gov

[Genetic basis for skeletal disease. CNP therapy for achondroplasia]. [2010]

5. United States pubmed.ncbi.nlm.nih.gov

A long-acting C-natriuretic peptide for achondroplasia. [2023]