A Clinical Trial to Evaluate Efficacy and Safety of TransCon CNP Compared With Placebo in Infants (0 to <2 Years of Age) With Achondroplasia

NCT06079398 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: ASND0030
• Study Type: interventional
• Target: 72
• Locations: 14 countries
• Sites: 17

Brief Summary

This trial is a Phase 2, multicenter, double-blind, randomized (ratio 2:1 TransCon CNP vs. placebo), placebo-controlled trial, designed to evaluate the safety, tolerability, and efficacy of 100 μg CNP/kg of Navepegritide (TransCon CNP) administered SC once-weekly for 52 weeks in infants with genetically verified heterozygous ACH, aged 0 to \< 2 years at the time of randomization.

Conditions

Achondroplasia

Outcome Measures

Primary Outcomes (2)

• To evaluate the safety and tolerability of Navepegritide

  Incidence of treatment emergent adverse events (TEAEs)

  52 weeks

• To evaluate the effect of Navepegritide on growth

  Change from baseline to 52 weeks in length/height Z-score

  52 weeks

Study Arms (2)

Navepegritide

EXPERIMENTAL

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

Drug: Navepegritide

Placebo for Navepegritide

PLACEBO COMPARATOR

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

Drug: Placebo for Navepegritide

Interventions

Navepegritide DRUG

Once-weekly subcutaneous injection of 100 µg/kg Navepegritide

Navepegritide

Placebo for Navepegritide DRUG

Once-weekly subcutaneous injection of 100 µg/kg placebo for Navepegritide

Placebo for Navepegritide

Eligibility Criteria

• Age: 0 Years - 2 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).
• Male or female younger than 2 years of age at the time of randomization; or for open label sentinel participants, at the time of first administration of IMP.
• Clinical diagnosis of achondroplasia (ACH) with genetic confirmation of heterozygous genotype present during screening.
• Parent(s)/caregiver(s) willing to follow the protocol and instructions provided, including being able to administer weekly subcutaneous injections of trial treatment.
• Compliance to daily Vitamin D supplementation for infants aged 14 days to 1 year. All participants older than 1 year of age with serum 25-hydroxyvitamin D (25OHD) measured below lower limit of reference range at screening should start daily Vitamin D supplementation prior to randomization.
• Considered eligible based on the medical history, physical examination, and the results of vital signs, ECG, imaging, and clinical laboratory tests performed during the screening period.

You may not qualify if:

• Known or suspected hypersensitivity to the investigational product or related products (trehalose, tris\[hydroxymethyl\]aminomethane, succinate, and polyethylene glycol \[PEG\]).
• Genetic confirmation of ACH homozygous genotype.
• Premature birth with gestational age \< 32 weeks.
• Premature birth with gestational age 32 to 37 weeks, unless time from birth is \> 6 months at the time of screening and the child is in good nutritional status, defined as gain in body weight expected for age and diagnosis of ACH, as determined by the Investigator and confirmed with the Medical Monitor.
• Anticipated, as assessed by Investigator and confirmed with Medical Monitor, to undergo surgical intervention during trial participation, including cervicomedullary decompression. Evaluation of immediate risk of requiring cervicomedullary decompression surgery will rely on the following assessments:
• Physical examination (e.g., neurologic findings of clonus, opisthotonus, exaggerated reflexes, dilated facial veins)
• Evidence of uncontrolled sleep apnea as confirmed by local standard of care assessment (e.g. polysomnography or simple sleep test) performed within 6 months prior to screening.
• MRI performed at screening indicating presence of severe cervicomedullary compression (CMC) or spinal cord damage. Presence of abnormal MRI T2 signal intensity at and immediately above and below the cervicomedullary junction should be considered high risk for requiring surgery and the participant is not eligible for trial participation.
• Common surgeries, such as insertion of grommets, adenoidectomy, tonsillectomy, or myringotomy tube placement are permitted during trial participation.
• Have a growth disorder or medical condition, other than ACH, resulting in short stature or abnormal growth as determined by the Investigator and confirmed with the Medical Monitor.
• Have received any dose of prescription medications and/or investigational medicinal product or device intended to affect stature, growth, or body proportionality (including human growth hormone or vosoritide) at any time.
• Requires or anticipated to require chronic (\> 4 weeks) or repeated treatment (more than twice/year) with oral corticosteroids, or high-dose inhaled corticosteroids during trial participation.
• History or presence of injury or disease of the growth plate(s), other than ACH, affecting growth potential of long bones, including Salter-Harris fracture and recent bone-related surgery, as determined by Investigator and confirmed with the Medical Monitor.
• Have a clinically significant finding indicating abnormal cardiac function, including but not limited to:
• Repaired or unrepaired coarctation.

Sponsors & Collaborators

• Ascendis Pharma A/S: lead

Study Sites (18)

Ascendis Investigational Site

Saint Paul, Minnesota, 55102, United States

RECRUITING

Ascendis Investigational Site

Houston, Texas, 77030, United States

RECRUITING

Ascendis Investigational Site

Madison, Wisconsin, 53705, United States

RECRUITING

Ascendis Investigational Site

Parkville, 3052, Australia

RECRUITING

Ascendis Investigational Site

Linz, 4020, Austria

RECRUITING

Ascendis Investigational Site

Montreal, H3T 1C5, Canada

RECRUITING

Ascendis Investigational Site

Copenhagen, 2100, Denmark

RECRUITING

Ascendis Investigational Site

Helsinki, 00029, Finland

RECRUITING

Ascendis Investigational Site

Paris, 75743, France

RECRUITING

Ascendis Investigational Site

Berlin, 13353, Germany

RECRUITING

Ascendis Investigational Site

Cologne, 50931, Germany

RECRUITING

Ascendis Investigational Site

Dublin, D01 YC76, Ireland

RECRUITING

Ascendis Investigational Site

Milan, 20132, Italy

RECRUITING

Ascendis Investigational Site

Auckland, 1023, New Zealand

RECRUITING

Ascendis Investigational Site

Oslo, 0372, Norway

RECRUITING

Ascendis Investigational Site

Coimbra, 3000-602, Portugal

RECRUITING

Ascendis Investigational Site

Stockholm, 17176, Sweden

RECRUITING

Ascendis Investigational Site

London, SE1 7EH, United Kingdom

RECRUITING

MeSH Terms

Conditions

Achondroplasia

Condition Hierarchy (Ancestors)

Dwarfism; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Osteochondrodysplasias; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Medical Director, MD

  Ascendis Pharma A/S

  STUDY DIRECTOR

Central Study Contacts

Ascendis Registry Inquiries

CONTACT

+45 61242484; asnd_registryinquiries@ascendispharma.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2023
• First Posted: October 12, 2023
• Study Start: January 23, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); PT (1); NO (1); SE (1); US (3); FR (1); DK (1); FI (1); IT (1); DE (2); IE (1); NZ (1); CA (1); GB (1)