TransCon CNP for Achondroplasia

(AttaCH Trial)

Enrolling by invitation at 16 trial locations

Overseen By Vibeke Breinholt

Age: < 18

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Ascendis Pharma Growth Disorders A/S

Must be taking: Vitamin D

Must not be taking: Prescription medications

Disqualifiers: Hypersensitivity, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 12

Duration: Individualized per participant, up to 10 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the efficacy and safety of TransCon CNP, a C-type natriuretic peptide prodrug, for children and teens with achondroplasia, a condition affecting bone growth. Participants will receive a once-weekly injection of TransCon CNP and continue treatment until reaching specific growth markers. This trial serves as a continuation for those who have completed a previous TransCon CNP trial. Ideal participants are children or teens with achondroplasia who have participated in a prior TransCon CNP trial and whose parents are comfortable administering weekly injections. As a Phase 2 and Phase 3 trial, this research assesses the treatment's effectiveness in a smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in achondroplasia treatment.

Will I have to stop taking my current medications?

The trial requires that participants have not received any dose of prescription medications or investigational products other than TransCon CNP. This suggests you may need to stop taking other medications, but the protocol does not specify a washout period.

Is there any evidence suggesting that TransCon CNP is likely to be safe for humans?

Research has shown that TransCon CNP is generally well-tolerated. Studies have found that most people experience few reactions at the injection site. Earlier research suggests that TransCon CNP is safe for children, as it releases the medication steadily, maintaining safe drug levels. These findings indicate that TransCon CNP could be a promising option for those with achondroplasia, with manageable side effects reported so far. ^{1 2 3 4 5}

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

Most treatments for achondroplasia, such as growth hormone therapy, focus on stimulating growth but have varying degrees of effectiveness and require frequent administration. TransCon CNP is unique because it uses a long-acting prodrug of C-type natriuretic peptide (CNP), which specifically targets pathways involved in bone growth and development. This treatment is delivered through a convenient once-weekly subcutaneous injection, potentially improving compliance compared to daily treatments. Researchers are excited because TransCon CNP has the potential to more effectively and consistently promote bone growth with fewer injections, providing a promising alternative for people with achondroplasia.

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

Research has shown that TransCon CNP can significantly increase growth rates in children with achondroplasia. Specifically, studies found that children receiving this treatment grew faster over a year compared to those who received a placebo. In this trial, participants will receive TransCon CNP 100 mcg once a week by subcutaneous injection. The treatment has demonstrated safety, with only a few side effects. TransCon CNP works by providing a steady supply of a substance that targets specific growth areas to help control bone growth. These findings suggest that this treatment could effectively manage growth in children with achondroplasia. ^{6 7 8 9 10}

Who Is on the Research Team?

Claus Strange

Principal Investigator

Ascendis Pharma A/S

Are You a Good Fit for This Trial?

This trial is for children and adolescents with achondroplasia who have already been part of a previous TransCon CNP study. They must be able to receive weekly injections, have parental consent, and meet safety criteria from the prior trial. Those unable to complete the study or at risk due to other conditions are excluded.

Inclusion Criteria

I have achondroplasia and finished a trial with TransCon CNP.

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

My guardian has signed the consent form, and I will too when I'm of age.

Exclusion Criteria

I have taken prescription or investigational drugs other than TransCon CNP.

I am not allergic to the trial drug or its components.

I am not using effective birth control and am able to have children.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weekly subcutaneous doses of TransCon CNP until femur and tibial epiphyseal closure is confirmed

Individualized per participant, up to 10 years

Visits every 12-14 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue receiving TransCon CNP in a long-term open-label extension

Up to 10 years

What Are the Treatments Tested in This Trial?

Interventions

• TransCon CNP

Trial Overview The long-term safety, tolerability, and effectiveness of TransCon CNP given once a week are being tested in young patients with achondroplasia until they reach skeletal maturity (16 years for females, 18 years for males), confirmed by radiographic imaging.

How Is the Trial Designed?

Group I: TransCon CNP 100 mcg Experimental Treatment 1 Intervention

TransCon CNP 100 mcg delivered once weekly by subcutaneous injection

Who Is Running the Clinical Trial?

Ascendis Pharma Growth Disorders A/S

Lead Sponsor

Trials

4

Recruited

320+

Published Research Related to This Trial

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]

Targeted overexpression of C-type natriuretic peptide (CNP) in chondrocytes effectively counteracts dwarfism in a mouse model of achondroplasia by preventing bone shortening and correcting extracellular matrix synthesis in the growth plate.

CNP works by inhibiting the MAPK pathway of FGF signaling, which is responsible for the bone growth issues in achondroplasia, suggesting that activating the CNP-GC-B system could be a promising new therapy for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overexpression of CNP in chondrocytes rescues achondroplasia through a MAPK-dependent pathway. Yasoda, A., Komatsu, Y., Chusho, H., et al.[2012]

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]

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, 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. rheumatologyadvisor.com rheumatologyadvisor.com/news/transcon-cnp-gets-priority-review-for-achondroplasia/

TransCon CNP Gets Priority Review for Achondroplasia “TransCon CNP is designed to provide sustained exposure to CNP, resulting in continuous inhibition of the fibroblast growth factor receptor 3 ( ...

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. sciencedirect.com sciencedirect.com/science/article/pii/S2589537023004352

Once-weekly TransCon CNP (navepegritide) in children ... 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 ...

8. ascendispharma.com ascendispharma.com/pipeline/endocrinology/transcon-cnp/

TransCon CNP TransCon CNP is an investigational prodrug of CNP in development for the treatment of ACH in children. Designed to provide continuous CNP exposure.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9796269/

Phase 1 safety, tolerability, pharmacokinetics and ... Further studies are ongoing to evaluate the potential of TransCon CNP to positively impact abnormal endochondral ossification in children with achondroplasia.

10. ascendispharma.us ascendispharma.us/wp-content/uploads/2020/09/TransCon-CNP-ACH-Mouse-Model_ASMBR-2017.pdf

TransCon CNP, a Sustained-Release Prodrug of C-Type ... TransCon CNP is a prodrug designed specifically to release free CNP at a slow rate, resulting in hemodynamically safe and efficacious drug levels employing a ...