TransCon CNP for Achondroplasia

(ApproaCH Trial)

Not currently recruiting at 11 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TransCon CNP, a C-type natriuretic peptide prodrug, to determine if it safely helps children with achondroplasia grow taller. The study compares the treatment's effects to a placebo over 52 weeks. After this period, all participants can receive the actual treatment for another 52 weeks in an open-label extension. Children aged 2 to 11 who can stand on their own and have a confirmed genetic diagnosis of achondroplasia may be eligible to join. As a Phase 2, Phase 3 trial, this research evaluates the treatment's effectiveness in a larger group and represents the final step before FDA approval, offering hope for an effective treatment.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that TransCon CNP is safe for children. Studies indicate it significantly aids growth in children with achondroplasia, with side effects similar to those of a sugar pill. Safety data from earlier trials confirmed it is generally safe when administered once a week. No major safety concerns have arisen, making it a promising treatment for promoting growth in affected children. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for achondroplasia?

Unlike the standard of care for achondroplasia, which typically involves surgical interventions or growth hormone treatments, TransCon CNP offers a novel approach. It is designed to target the fibroblast growth factor receptor 3 (FGFR3) pathway, which is overactive in individuals with achondroplasia, by delivering C-type natriuretic peptide (CNP) in a sustained manner. This allows for potentially more precise regulation of bone growth. Administered via a once-weekly subcutaneous injection, TransCon CNP provides a less invasive option compared to surgery and a more targeted mechanism than general growth hormones. Researchers are excited about its potential to directly address the underlying cause of the condition rather than just its symptoms.

What evidence suggests that TransCon CNP might be an effective treatment for Achondroplasia?

Research has shown that TransCon CNP, one of the treatments in this trial, can help children with achondroplasia, a genetic condition affecting bone growth, increase in height. Studies found that children taking TransCon CNP grew faster each year compared to those receiving a placebo, another treatment arm in this trial. TransCon CNP works by steadily releasing C-type natriuretic peptide, which helps regulate bone growth. Importantly, the safety profile of TransCon CNP is similar to that of a placebo, with few cases of mild reactions at the injection site. These early results suggest it could be a promising once-a-week option for aiding growth in children with achondroplasia. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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: Open-Label Extension Period: TransCon CNP Experimental Treatment 1 Intervention

Participants who completed the 52-week blinded treatment period continued into the open-label extension period and received treatment with TransCon CNP 100 µg/kg delivered once weekly by subcutaneous injection.

Group III: 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+

Published Research Related to This Trial

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]

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]

Citations

1. investors.ascendispharma.com investors.ascendispharma.com/news-releases/news-release-details/new-data-shows-improvements-growth-and-bone-morphometry-children

New Data Shows Improvements in Growth and Bone ... TransCon CNP demonstrated superiority over placebo in annualized growth velocity (AGV), with a safety and tolerability profile comparable to placebo.

2. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00435-2/fulltext

Once-weekly TransCon CNP (navepegritide) in children ... This trial provides the first evidence that TransCon CNP significantly increased annualised growth velocity in children with achondroplasia with a favourable ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37823031/

Once-weekly TransCon CNP (navepegritide) in children with ... This phase 2 trial suggests that TransCon CNP is effective, safe, with low injection site reaction frequency, and may provide a novel, once-weekly treatment ...

4. asbmr.confex.com asbmr.confex.com/asbmr/2025/meetingapp.cgi/Paper/5355

26-Week Results from the Phase 2 COACH Trial Conclusions These 26-week data demonstrate that treatment with once-weekly lonapegsomatropin co-administered with once-weekly navepegritide ...

5. investors.ascendispharma.com investors.ascendispharma.com/news-releases/news-release-details/ascendis-submits-marketing-authorisation-application-european

News Release TransCon CNP is an investigational prodrug of C-type natriuretic peptide (CNP) administered once weekly, designed for continuous inhibition ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35481707/

Phase 1 safety, tolerability, pharmacokinetics and ... Safety and PD data from this phase 1 trial support that TransCon CNP is well tolerated, with a PK profile compatible with a once-weekly dosing regimen.

7. bpspubs.onlinelibrary.wiley.com bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.15369

Phase 1 Safety, Tolerability, PK/PD of TransCon CNP Safety and PD data from this phase 1 trial support that TransCon CNP is well tolerated, with a PK profile compatible with a once-weekly dosing ...