A Phase 2 Clinical Trial to Evaluate Efficacy, Safety, and Tolerability of Navepegritide in Combination With Lonapegsomatropin in Children With Achondroplasia

NCT06433557 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: ASND0042
• Study Type: interventional
• Target: 22
• Locations: 3 countries
• Sites: 3

Brief Summary

This proof-of-concept trial is being conducted to evaluate the efficacy, safety and tolerability of combination treatment with navepegritide and lonapegsomatropin administered as separate subcutaneous (SC) injections once weekly in children with achondroplasia (ACH) aged 2 to 11 years.

Conditions

Achondroplasia

Outcome Measures

Primary Outcomes (2)

• Annualized growth velocity

  cm per year, compared to navepegritide alone

  Week 52

• Treatment-emergent adverse events (TEAEs).

  safety profile of navepegritide and lonapegsomatropin

  Throughout the trial for 156 weeks

Secondary Outcomes (1)

• Annualized growth velocity

  From start until 156 weeks

Study Arms (1)

Combination of Navepegritide and Lonapegsomatropin

EXPERIMENTAL

Drug: Combination of Navepegritide and Lonapegsomatropin administered as two separate s.c. injections

Interventions

Combination of Navepegritide and Lonapegsomatropin administered as two separate s.c. injections DRUG

For navepegritide, a once weekly s.c. dose of 100 μg CNP/kg. For lonapegsomatropin, a once weekly s.c. dose of lonapegsomatropin 0.30 mg hGH/kg as starting dose. Treatment duration of up to 156 weeks.

Combination of Navepegritide and Lonapegsomatropin

Eligibility Criteria

• Age: 2 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Written, signed informed consent and/or assent (if applicable) by the parent(s) or legal representative(s) of the participant, and as required by the IRB/HREC/IEC.
• Male or female between 2 to 11 years of age (inclusive) at the time of Visit 1.
• Clinical diagnosis of ACH with genetic confirmation of heterozygote genotype present at Visit 1. Documentation of historic test results are acceptable for proof of diagnosis.
• Able to stand without assistance.
• Parent(s)/caregiver(s)/legal guardian(s) willing and able to administer weekly SC injections of IMP and comply with all protocol requirements.
• At least 6 months of growth and disease history from TCC-NHS-01 or TCC-201 or comparable growth and disease history available from medical records.
• No intracranial pathology as confirmed by brain MRI (historical MRI obtained within 2 years prior to screening allowable).

You may not qualify if:

• Participation in any interventional clinical trial within three months prior to screening (except TCC-201 or ASND0039).
• Closed epiphysis at screening.
• History of or suspected hypersensitivity to the IMP or related products.
• Findings on fundoscopy at screening consistent with intracranial hypertension, papilledema, or evidence of any other retinal disease for which GH therapy is contraindicated.
• Have 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, GHD, Turner syndrome, pseudoachondroplasia, inflammatory bowel disease, celiac disease, hypothyroidism, hyperthyroidism, pre-diabetes, or diabetes mellitus.
• Have received any dose of prescription and/or investigational medications or device intended to affect stature, growth, or body proportionality at any time prior to screening.
• Receiving concurrent treatment with any agent that might influence growth or interfere with GH secretion or action:
• Inhaled corticosteroid therapy at a dose of \>400 µg/day of inhaled budesonide or equivalent for more than 28 consecutive days total over the course of 12 months prior to screening.
• Require, 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.
• Currently using or have used within 12 months prior to screening any sex steroids (for example estrogen), non-steroidal anabolic agents (for example, oxandrolone) or gonadotropin-releasing hormone (GnRH) analogues treatment.
• Treatment for attention-deficit hyperactive disorder (ADHD) such as methylphenidate.
• Known history or presence of injury or disease of the growth plate(s), other than ACH, that affects growth potential of long bones.
• Cervicomedullary decompression surgery within 6 months prior to Screening or with anticipated need for repeat decompression surgery during the time of the trial.
• Evidence at screening consistent with severe cervicomedullary junction compression based on clinical and/or radiologic findings that indicate immediate surgical intervention is required.
• Ventriculoperitoneal shunt and laminectomy with full recovery within 6 months prior to Screening.

Sponsors & Collaborators

• Ascendis Pharma Growth Disorders A/S: lead

Study Sites (3)

Ascendis Pharma Investigational Site

Copenhagen, 2100, Denmark

Location

Ascendis Pharma Investigational Site

Dublin, D01 YC76, Ireland

Location

Ascendis Pharma Investigational Site

London, W1W 5AH, United Kingdom

Location

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2024
• First Posted: May 29, 2024
• Study Start: July 26, 2024
• Primary Completion: November 14, 2025
• Study Completion (Estimated): November 1, 2027
• Last Updated: February 18, 2026

Record last verified: 2026-02

Locations

IE (1); DK (1); GB (1)