Navepegritide for Achondroplasia

Recruiting at 17 trial locations

Overseen By Ascendis Registry Inquiries

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Ascendis Pharma A/S

Must be taking: Vitamin D

Must not be taking: Corticosteroids, Growth hormone

Disqualifiers: Premature birth, Surgery, 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

72 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called Navepegritide (TransCon CNP) for infants with achondroplasia, a genetic condition affecting bone growth. Researchers aim to determine the treatment's safety and effectiveness by comparing it to a placebo (a substance with no active medicine) over 52 weeks. The trial seeks infants under 2 years old diagnosed with achondroplasia who can receive weekly injections. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to important early findings.

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 taking medications that affect growth or require long-term corticosteroid use, you may not be eligible to participate.

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

Research has shown that TransCon CNP, also known as navepegritide, is generally safe for children. Studies have found it well-tolerated, with side effects similar to those of a placebo, meaning they are not much different from a dummy treatment. Few reports exist of mild reactions at the injection site, and these are uncommon.

Children who used TransCon CNP showed improvements without major safety issues. The treatment involves a once-a-week injection, designed for easy management.

In summary, current evidence supports its safety for children, making it a promising option for those considering joining a clinical trial. ^{1 2 3 4 5}

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

Navepegritide is unique because it acts as a C-type natriuretic peptide (CNP) analog, offering a new approach to treating achondroplasia. Unlike the standard of care, which typically involves growth hormone therapy, Navepegritide targets a different pathway by enhancing bone growth through its specific action on the FGFR3 pathway. Researchers are excited about this treatment because its weekly subcutaneous injection could potentially improve growth velocity and bone development more effectively and with fewer side effects than current options.

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

Research has shown that TransCon CNP (Navepegritide) can help children with achondroplasia grow faster. In studies, children who received Navepegritide grew taller and showed improved bone development. Participants in this trial will receive either Navepegritide or a placebo once a week. The treatment is generally well-tolerated, with few reactions at the injection site. It works by blocking a pathway that affects bone growth, aiding in height increase. These findings suggest that Navepegritide could be a promising new option for managing achondroplasia. ^{2 4 6 7 8}

Who Is on the Research Team?

Medical Director, MD

Principal Investigator

Ascendis Pharma A/S

Are You a Good Fit for This Trial?

This trial is for infants under 2 years with achondroplasia, a form of dwarfism. Parents must consent and be able to give weekly shots at home. Babies up to 1 year old need daily Vitamin D; older ones with low levels must start supplements before joining.

Inclusion Criteria

I am under 2 years old.

My caregiver is ready to follow the study rules and give me weekly shots.

Written, signed informed consent by the parent(s)/caregiver(s) of the participant, and as required by the institutional review board/human research ethics committee/independent ethics committee (IRB/HREC/IEC)

Exclusion Criteria

My genetic test shows I have two copies of the ACH gene.

Known or suspected hypersensitivity to the investigational product or related products (trehalose, tris[hydroxymethyl]aminomethane, succinate, and polyethylene glycol [PEG])

History or presence of injury or disease of the growth plate(s), other than ACH, affecting growth potential of long bones, as determined by Investigator and confirmed with the Medical Monitor

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weekly subcutaneous injections of TransCon CNP or placebo for 52 weeks

52 weeks

Once weekly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may opt into continuation of treatment long-term

What Are the Treatments Tested in This Trial?

Interventions

• TransCon CNP

Trial Overview The trial tests Navepegritide (TransCon CNP) against a placebo in babies with achondroplasia. It's given as a shot once a week for a year. The goal is to see if it's safe and works better than no treatment.

How Is the Trial Designed?

Group I: Navepegritide Experimental Treatment 1 Intervention

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

Group II: Placebo for Navepegritide Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Ascendis Pharma A/S

Lead Sponsor

Trials

15

Recruited

1,600+

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]

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 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]

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 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]

Systemic administration of C-type natriuretic peptide (CNP) significantly improved bone growth in a mouse model of achondroplasia, a common skeletal dysplasia, suggesting its potential as a novel treatment.

The study showed that both increased plasma CNP from the liver and intravenous administration of synthetic CNP-22 effectively rescued impaired bone growth without significant adverse effects, indicating a promising therapeutic strategy for skeletal dysplasias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic administration of C-type natriuretic peptide as a novel therapeutic strategy for skeletal dysplasias. Yasoda, A., Kitamura, H., Fujii, T., et al.[2021]

C-type natriuretic peptide (CNP) promotes skeletal growth and can rescue dwarfism in a transgenic model of achondroplasia, indicating its potential as a treatment for this condition.

In a specially designed mouse model with high blood CNP levels, skeletal overgrowth occurred without negative effects on blood pressure or heart weight, suggesting that CNP could stimulate bone growth safely.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronically elevated plasma C-type natriuretic peptide level stimulates skeletal growth in transgenic mice. Kake, T., Kitamura, H., Adachi, Y., et al.[2009]

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 ... New Data Shows Improvements in Growth and Bone Morphometry in Children with Achondroplasia Treated with TransCon® CNP (Navepegritide). May 13, ...

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10562841/

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 ...

7. 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.

8. rarediseaseadvisor.com rarediseaseadvisor.com/news/trial-assessing-safety-and-efficacy-of-transcon-cnp-in-achondroplasia-completed/

Dose-Escalation Trial of TransCon CNP in Achondroplasia ... A clinical trial assessing the safety and efficacy of TransCon CNP in children with achondroplasia has been completed.