AchondroplasiaPhase 2/3ApproaCHNCT05598320
A Clinical Trial to Evaluate Efficacy and Safety of TransCon CNP Compared With Placebo in Children With Achondroplasia
A Phase 2/3 study testing Navepegritide (TransCon CNP) in people with Achondroplasia, run by Ascendis Pharma Growth Disorders A/S at 10 sites in 7 countries.
Trial summary
The purpose of this clinical trial was to evaluate efficacy and safety of once weekly subcutaneous (SC) doses of 100 µg TransCon CNP/kg compared to placebo on Annualized Growth Velocity after a 52-week randomized treatment period in children aged 2 to 11 years with genetically confirmed Achondroplasia. Read more about this study
- Who is it for?
- Ages 2 to 11 years
- Conditions the study is for
- Achondroplasia
- What is being tested?
- Navepegritide (TransCon CNP)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 84 participants
- Where
- 10 sitesin 7 countries
- Study dates
- 3 Mar 2023to 13 Aug 2025
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 11 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Written, signed informed consent of the parent(s) or legal guardian(s) of the participant, and as required by the institutional review board/human research ethics committee/independent ethics committee (IRB/HREC/IEC).
- Male or female, between 2 and 11 years of age (inclusive) at the time of Screening.
- Clinical diagnosis of Achondroplasia (ACH) with documented genetic confirmation available.
- Able to stand without assistance.
- Parent(s)/legal guardian(s) willing and able to administer weekly SC injections of Investigational Medicinal Product (IMP) and to follow the protocol.
- At least six months of growth and disease history from ACHieve (TCC-NHS-01) trial or comparable growth and disease history available from medical records (pending confirmation by Medical Monitor).
- Considered eligible based on the medical history, physical examination, and the results of vital signs, ECG and clinical laboratory tests performed during the Screening period
Who cannot join
- Participation (i.e., signed informed consent) in any interventional clinical trial before within 3 months prior to screening.
- Closed epiphysis.
- Known or suspected hypersensitivity to the IMP or related products (trehalose, tris[hydroxymethyl]aminomethane, succinate, and mPEG).
- Had a growth disorder or medical condition other than ACH that results in short stature or abnormal growth such as severe ACH with developmental delay and acanthosis nigricans (SADDAN), hypochondroplasia, growth hormone deficiency, Turner syndrome, pseudoachondroplasia, inflammatory bowel disease, celiac disease, hypothyroidism, hyperthyroidism, pre-diabetes, or diabetes mellitus.
- Have received any dose of prescription medications and IMP or surgical intervention intended to affect stature, growth, or body proportionality at any time.
- Required, or anticipated to require, chronic (> 4 weeks) or repeated treatment (more than twice/year and >3 weeks/year) with systemic corticosteroids during participation in the trial. Chronic use of high-dose inhaled corticosteroids was not allowed.
Show all 31Show fewer
- Known history of presence of injury or disease of the growth plate(s), other than ACH, that affects growth potential of long bones.
- Known history of any bone-related surgery affecting growth potential of long bones, such as:
- Orthopedic reconstructive surgery for bone lengthening (e.g., procedures for leg bowing such as 8-plate are not exclusionary).
- Cervicomedullary decompression surgery without anticipated need for repeat decompression during the time of the trial are allowed with minimum of 6 months of bone healing.
- Ventriculoperitoneal (VP) shunt and laminectomy with full recovery are allowed with minimum of 6 months of bone healing.
- Bone fracture within 6 months prior to screening (within 2 months for fracture of digits and buckle fractures).
- Clinically significant findings at Screening, such as:
- Expected to require surgical intervention during participation in the trial. Common surgeries, such as insertion of grommets, adenoidectomy, tonsillectomy, or myringotomy tube placement, are permitted.
- Severe untreated sleep apnea or newly initiated sleep apnea treatment (e.g., Continuous Positive Airway Pressure [CPAP] in the previous 2 months prior to Screening).
- Musculoskeletal disease, such as Salter-Harris fractures or clinical and/or radiographic evidence of severe hip pathology, or
- Otherwise, are considered by the Investigator and Medical Monitor to make a participant unfit to receive trial treatment or undergo trial related procedures.
- Had evidence at Screening that were consistent with severe cervicomedullary junction compression based on clinical and/or radiologic findings that indicated immediate surgical intervention was required.
- Had a clinically significant finding or arrhythmia as determined by the investigator in consultation with the medical monitor that indicates abnormal cardiac function or conduction that includes, but was not exclusive to:
- Repaired or unrepaired coarctation.
- Moderate or greater complexity congenital heart disease including tetralogy of Fallot, Atrioventricular septal defects, truncus arteriosus, total anomalous pulmonary venous return, double outlet right ventricle, or single ventricle heart disease.
- QTcF ≥ 450 msec at the Screening Visit.
- Known history or presence of condition that impacts hemodynamic stability (such as autonomic dysfunction and orthostatic intolerance).
- Known history or presence of the following:
- Chronic anemia (iron deficiency anemia that is resolved or adequately treated in the Investigator's opinion was allowed).
- Chronic renal insufficiency (GFR <60 mL/min/1.73 m2 for >3 months).
- Chronic or recurrent illness that can affect hydration or volume status, including conditions associated with decreased nutritional intake or increased volume loss.
- Known history or presence of malignant disease.
- Participant with serum 25-hydroxy-vitamin D (25OHD) levels of <30 nmol/L (<12 ng/mL) at Screening Visit were excluded. Participants with 25OHD levels between 30-50 nmol/L (12-20 ng/mL) were randomized provided treatment with Vitamin D supplementation was initiated.
- Any disease or condition that, in the opinion of the Investigator, may make the participant unlikely to fully complete the trial, may confound interpretation of trial results, or may present undue risk from receiving trial treatment. This included family situations, complications or manifestations, or medications that might impact safety or be considered confounding.
- Sexually active male and female participants and female partners of male participants of childbearing potential not using a highly effective form of contraceptive for the entire trial period and for 90 days after last dose of trial treatment.
Trial locations and contacts
10 sites in 7 countries.
10 sites in 7 countries
United States4 sites
Ascendis Pharma Investigational Site
Columbia, Missouri, 65212
Ascendis Pharma Investigational Site
Houston, Texas, 77030
Ascendis Pharma Investigational Site
Madison, Wisconsin, 53705
Ascendis Pharma Investigational Site
Saint Paul, Minnesota, 55102
About this study
Official title: A Phase 2b, Multicenter, Double-Blind, Randomized, Placebo-controlled Trial Evaluating Efficacy and Safety of Subcutaneous Doses of TransCon CNP Administered Once Weekly for 52 Weeks in Children With Achondroplasia Followed by an Open Label Extension Period
The purpose of this clinical trial was to evaluate efficacy and safety of once weekly subcutaneous (SC) doses of 100 µg TransCon CNP/kg compared to placebo on Annualized Growth Velocity after a 52-week randomized treatment period in children aged 2 to 11 years with genetically confirmed Achondroplasia. The double-blind, placebo-controlled treatment period was followed by an Open Label Extension (OLE) period of a 52-week duration.
- Conditions
- Achondroplasia
- Being tested
- Navepegritide (TransCon CNP), Placebo for Navepegritide (TransCon CNP)
- Medical subject headings
- Achondroplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Navepegritide (TransCon CNP)Drug
Once-weekly subcutaneous injection of 100 µg/kg Navepegritide (TransCon CNP)
Placebo for Navepegritide (TransCon CNP)Drug
Once-weekly subcutaneous injection of 100 µg/kg placebo for Navepegritide (TransCon CNP)
| Study group | Role | What they receive |
|---|---|---|
| Navepegritide | Experimental | Participants received Navepegritide (TransCon CNP) 100 micrograms per kilogram (µg/kg) delivered once weekly by subcutaneous injection for a treatment period of up to 52 weeks. Receives: Drug: Navepegritide (TransCon CNP) |
| Placebo for Navepegritide | Placebo comparator | Participants received placebo matched for Navepegritide (TransCon CNP) 100 µg/kg delivered once weekly by subcutaneous injection for a treatment period of up to 52 weeks. Receives: Drug: Placebo for Navepegritide (TransCon CNP) |
| Open-Label Extension Period: Navepegritide | Experimental | Participants who completed the 52-week treatment period continued into the open-label extension period and received treatment with navepegritide (TransCon CNP) doses up to Week 104. All participants received navepegritide at a dose of 100 μg/kg/week. Receives: Drug: Navepegritide (TransCon CNP) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Annualized Growth Velocity (AGV) at Week 52
Annualized growth velocity is defined as (height - baseline height)/(date of height assessment - date of baseline) * 365.25. Annualized growth velocity reported in terms of centimeters (cm) per year. Missing values at Week 52 were imputed by a multiple imputation method.
Measured: At Week 52
Secondary outcomes (2)
Change From Baseline in Height Z-score (ACH-specific) at Week 52
ACH specific Z-scores of height provide a measure of growth relative to other individuals with ACH from the CLARITY database. A height Z-score is a standardized height measure after considering important factors like age and gender. Z-scores (or standard deviation scores) describe how far the measurement deviates from the mean. A height Z-score of 0 indicates that height is equal to the mean in the reference population. Negative numbers indicate values below the mean and positive numbers indicate values above the mean.
Measured: Baseline, Week 52
Change From Baseline in Height Z-score (CDC-Based) at Week 52
Z-scores of height are determined using Centers for Disease Control and Prevention (CDC) clinical growth charts for children. A height Z-score is a standardized height measure after considering important factors like age and gender. Z-scores (or standard deviation scores) describe how far the measurement deviates from the median. A height Z-score of 0 indicates that height is equal to the median in the reference population. Negative numbers indicate values below the median and positive numbers indicate values above the median.
Measured: Baseline, Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2022
- Study start3 Mar 2023
- Primary completion9 Aug 2024
- Study completion13 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for AchondroplasiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ascendis Pharma Growth Disorders A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, MD, Study director, Ascendis Pharma A/S
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05598320
- Sponsor's protocol ID
- ASND0036
- Acronym
- ApproaCH
- Status last verified
- Jun 2026
- First submitted
- 25 Oct 2022
- Last updated
- 14 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Not planned
Publications
McDonnell CM, Irving M, Nolting LA, Abdelrahman SG, Dalby LW, Ikle JM, Jensen SM, Komirenko AS, Ominsky MS, Shu AD, Hove HB. Navepegritide combined with lonapegsomatropin for the treatment of children with achondroplasia: 52-week results from the phase 2 COACH trial. Eur J Endocrinol. 2026 Jun 1;194(6):745-755. doi: 10.1093/ejendo/lvag082.
PubMed 42144862Savarirayan R, McDonnell C, Bacino CA, Hoernschemeyer DG, Legare JM, Abuzzahab MJ, Hofman PL, Campeau PM, de Bergua Domingo JM, Ward LM, Smit K, Smith A, Mao M, Ominsky MS, Freiberg LC, Shu AD, Hove HB. Once-Weekly Navepegritide in Children With Achondroplasia: The APPROACH Randomized Clinical Trial. JAMA Pediatr. 2026 Jan 1;180(1):18-25. doi: 10.1001/jamapediatrics.2025.4771.
PubMed 41247754
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2b, Multicenter, Double-Blind, Randomized, Placebo-controlled Trial Evaluating Efficacy and Safety of Subcutaneous Doses of TransCon CNP Administered Once Weekly for 52 Weeks in Children With Achondroplasia Followed by an Open Label Extension Period
- ClinicalTrials.gov ID
- NCT05598320
- Acronym / sponsor ID
- ApproaCH / ASND0036
- Conditions
- Achondroplasia
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Ascendis Pharma Growth Disorders A/SIndustry (pharma, biotech, devices)
- Study start
- 3 Mar 2023 (actual)
- Primary completion
- 9 Aug 2024 (actual)
- Study completion
- 13 Aug 2025 (actual)
- First posted
- 28 Oct 2022 (actual)
- Results
- Posted 14 Jul 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this clinical trial was to evaluate efficacy and safety of once weekly subcutaneous (SC) doses of 100 µg TransCon CNP/kg compared to placebo on Annualized Growth Velocity after a 52-week randomized treatment period in children aged 2 to 11 years with genetically confirmed Achondroplasia. The double-blind, placebo-controlled treatment period was followed by an Open Label Extension (OLE) period of a 52-week duration.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Navepegritide | Experimental | Drug: Navepegritide (TransCon CNP)Participants received Navepegritide (TransCon CNP) 100 micrograms per kilogram (µg/kg) delivered once weekly by subcutaneous injection for a treatment period of up to 52 weeks. |
| Placebo for Navepegritide | Placebo comparator | Drug: Placebo for Navepegritide (TransCon CNP)Participants received placebo matched for Navepegritide (TransCon CNP) 100 µg/kg delivered once weekly by subcutaneous injection for a treatment period of up to 52 weeks. |
| Open-Label Extension Period: Navepegritide | Experimental | Drug: Navepegritide (TransCon CNP)Participants who completed the 52-week treatment period continued into the open-label extension period and received treatment with navepegritide (TransCon CNP) doses up to Week 104. All participants received navepegritide at a dose of 100 μg/kg/week. |
Who may qualify
- Ages
- 2 to 11 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Written, signed informed consent of the parent(s) or legal guardian(s) of the participant, and as required by the institutional review board/human research ethics committee/independent ethics committee (IRB/HREC/IEC).
- Male or female, between 2 and 11 years of age (inclusive) at the time of Screening.
- Clinical diagnosis of Achondroplasia (ACH) with documented genetic confirmation available.
- Able to stand without assistance.
- Parent(s)/legal guardian(s) willing and able to administer weekly SC injections of Investigational Medicinal Product (IMP) and to follow the protocol.
Key exclusion criteria (31 listed)
- Participation (i.e., signed informed consent) in any interventional clinical trial before within 3 months prior to screening.
- Closed epiphysis.
- Known or suspected hypersensitivity to the IMP or related products (trehalose, tris[hydroxymethyl]aminomethane, succinate, and mPEG).
- Had a growth disorder or medical condition other than ACH that results in short stature or abnormal growth such as severe ACH with developmental delay and acanthosis nigricans (SADDAN), hypochondroplasia, growth hormone deficiency, Turner syndrome, pseudoachondroplasia, inflammatory bowel disease, celiac disease, hypothyroidism, hyperthyroidism, pre-diabetes, or diabetes mellitus.
- Have received any dose of prescription medications and IMP or surgical intervention intended to affect stature, growth, or body proportionality at any time.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Navepegritide (TransCon CNP)Once-weekly subcutaneous injection of 100 µg/kg Navepegritide (TransCon CNP) | Drug | Navepegritide, Open-Label Extension Period: Navepegritide |
| Placebo for Navepegritide (TransCon CNP)Once-weekly subcutaneous injection of 100 µg/kg placebo for Navepegritide (TransCon CNP) | Drug | Placebo for Navepegritide |
Primary outcome
Annualized Growth Velocity (AGV) at Week 52
Time frame: At Week 52
Annualized growth velocity is defined as (height - baseline height)/(date of height assessment - date of baseline) * 365.25. Annualized growth velocity reported in terms of centimeters (cm) per year. Missing values at Week 52 were imputed by a multiple imputation method.
2 secondary outcomes
Change From Baseline in Height Z-score (ACH-specific) at Week 52
Time frame: Baseline, Week 52
Change From Baseline in Height Z-score (CDC-Based) at Week 52
Time frame: Baseline, Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42144862McDonnell CM, Irving M, Nolting LA, Abdelrahman SG, Dalby LW, Ikle JM, Jensen SM, Komirenko AS, Ominsky MS, Shu AD, Hove HB. Navepegritide combined with lonapegsomatropin for the treatment of children with achondroplasia: 52-week results from the phase 2 COACH trial. Eur J Endocrinol. 2026 Jun 1;194(6):745-755. doi: 10.1093/ejendo/lvag082.
- Derived from this study: PubMed 41247754Savarirayan R, McDonnell C, Bacino CA, Hoernschemeyer DG, Legare JM, Abuzzahab MJ, Hofman PL, Campeau PM, de Bergua Domingo JM, Ward LM, Smit K, Smith A, Mao M, Ominsky MS, Freiberg LC, Shu AD, Hove HB. Once-Weekly Navepegritide in Children With Achondroplasia: The APPROACH Randomized Clinical Trial. JAMA Pediatr. 2026 Jan 1;180(1):18-25. doi: 10.1001/jamapediatrics.2025.4771.
- Individual participant dataSharing planned: No. Not planned
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director, MD study director
Ascendis Pharma A/S
10 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Navepegritide (TransCon CNP) in people with Achondroplasia, run by Ascendis Pharma Growth Disorders A/S at 10 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Australia, Canada, Denmark, Ireland and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Annualized Growth Velocity (AGV) at Week 52 (time frame: At Week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05598320, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2026.