NAVEPEGRITIDE for Achondroplasia

Inclusion criteria

• {"criterion_text":"- 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).\n- 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.\n- Clinical diagnosis of achondroplasia (ACH) with genetic confirmation of heterozygous genotype present during screening.\n- Parent(s)/caregiver(s) willing to follow the protocol and instructions provided, including being able to administer weekly subcutaneous injections of trial treatment.\n- 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.\n- 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\n- Not eligible for treatment with vosoritide for any of the following reasons: − vosoritide is not available (licensed) in the country where the participant resides or not available (licensed) for the age of the participant, − the participant’s parents(s)/caregiver(s) are not willing to initiate treatment with vosoritide despite being thoroughly informed by the investigator of the benefits and risks of vosoritide treatment, − the participant’s parent(s)/caregiver(s) does not have the possibility to cover any expenses related to vosoritide treatment if not fully reimbursed in the country where the participant resides."}

Exclusion criteria

• {"criterion_text":"- Known or suspected hypersensitivity to the investigational product or related products (trehalose, tris[hydroxymethyl]aminomethane, succinate, and polyethylene glycol [PEG])\n- Have a clinically significant finding indicating abnormal cardiac function, including but not limited 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 on screening 12-lead ECG.\n- History or presence of a condition impacting hemodynamic stability (such as autonomic dysfunction and orthostatic intolerance).\n- History or presence of the following: • Chronic anemia. • Chronic renal insufficiency. • Chronic or recurrent illness that can affect hydration or volume status, including conditions associated with decreased nutritional intake or increased volume loss.\n- History or presence of malignant disease.\n- Any disease or condition that, in the opinion of the Investigator, may make the participant unlikely to fully complete the trial, not adhering to trial procedures, may confound interpretation of trial results, or may present undue risk from receiving trial treatment. This could include family situations, comorbid conditions, or medications that might impact safety or be considered confounding.\n- Genetic confirmation of ACH homozygous genotype\n- Premature birth with gestational age < 32 weeks.\n- 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.\n- 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.\n- 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\n- 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.\n- 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.\n- 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."}

Primary endpoints

• {"endpoint_text":"- Incidence of treatment emergent adverse events (TEAEs) over 52 weeks, including Grade ≥ 3 TEAEs; serious adverse events (SAEs); TEAEs leading to discontinuation; deaths due to TEAEs, and all deaths","definition_or_measurement_approach":"Safety assessment over 52 weeks collecting TEAEs, Grade ≥3 TEAEs, SAEs, TEAEs leading to discontinuation, and deaths as reported by investigators during the 52-week treatment period."}
• {"endpoint_text":"- Change from baseline to 52 weeks in length/height Z-score","definition_or_measurement_approach":"Anthropometric measurement of length/height converted to Z-score and change from baseline to week 52."}

Secondary endpoints

• {"endpoint_text":"- Annualized growth velocity (AGV) (cm/year) at 52 weeks and 104 weeks","definition_or_measurement_approach":"Measurement of growth in cm/year (AGV) at weeks 52 and 104."}
• {"endpoint_text":"- Change from baseline to 104 weeks in length/height Z-score","definition_or_measurement_approach":"Anthropometric change in length/height Z-score from baseline to week 104."}
• {"endpoint_text":"- Change from baseline to 52 weeks and 104 weeks in Bayley Scales, motor and language scales (4th edition)","definition_or_measurement_approach":"Assessment using Bayley Scales (4th edition) motor and language subscales at weeks 52 and 104 compared to baseline."}
• {"endpoint_text":"- Change from baseline to 52 weeks and 104 weeks in evaluation (X-ray) of long bones and angles in lower limbs (e.g., femur, tibia, fibula, and tibia/fibula and femur/tibia ratio, mechanical axis deviations)","definition_or_measurement_approach":"Radiographic evaluation (X-ray) of long bones and angular measurements (examples listed) at weeks 52 and 104 compared to baseline."}
• {"endpoint_text":"- Change from baseline to 52 weeks and 104 weeks in evaluation of MRI of spine (e.g., spine interpedicular distance (IPD), spine pedicle width (PW), spinal cord volume, and ratio of area of spinal cord to spinal canal)","definition_or_measurement_approach":"MRI measurements of spinal metrics (IPD, PW, spinal cord volume, area ratios) at weeks 52 and 104 vs baseline."}
• {"endpoint_text":"- Change from baseline to 52 weeks and 104 weeks in evaluation of MRI of foramen magnum (e.g., sagittal and transverse diameters, surface area (cm2 ) of foramen magnum, ratio of spinal cord to foramen magnum area, and Achondroplasia Foramen Magnum Score (AFMS))","definition_or_measurement_approach":"MRI evaluation of foramen magnum dimensions and derived metrics (including AFMS) at weeks 52 and 104 compared to baseline."}
• {"endpoint_text":"- Incidence of complications and manifestations of ACH, for example, breathing related sleep disorder, otitis media, hearing loss, musculoskeletal (MS) pain and MS deformities, ACH-related TEAEs reported by investigators","definition_or_measurement_approach":"Recording incidence of specified ACH-related complications and investigator-reported ACH-related TEAEs during follow-up."}

Spain

Earliest CTIS Part Ii Submission Date

07-02-2024

Latest Decision Or Authorization Date

15-01-2026

Processing Time Days

708

Number Of Sites

1

Number Of Participants

5

Norway

Earliest CTIS Part Ii Submission Date

18-03-2024

Latest Decision Or Authorization Date

13-01-2026

Processing Time Days

666

Number Of Sites

1

Number Of Participants

5

Germany

Earliest CTIS Part Ii Submission Date

18-03-2024

Latest Decision Or Authorization Date

13-01-2026

Processing Time Days

666

Number Of Sites

2

Number Of Participants

10

Ireland

Earliest CTIS Part Ii Submission Date

11-03-2024

Latest Decision Or Authorization Date

12-01-2026

Processing Time Days

672

Number Of Sites

1

Number Of Participants

6

France

Earliest CTIS Part Ii Submission Date

13-03-2024

Latest Decision Or Authorization Date

09-01-2026

Processing Time Days

667

Number Of Sites

1

Number Of Participants

6

Finland

Earliest CTIS Part Ii Submission Date

04-02-2025

Latest Decision Or Authorization Date

09-01-2026

Processing Time Days

339

Number Of Sites

1

Number Of Participants

4

Sweden

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

09-01-2026

Processing Time Days

661

Number Of Sites

1

Number Of Participants

5

Austria

Earliest CTIS Part Ii Submission Date

04-04-2024

Latest Decision Or Authorization Date

12-01-2026

Processing Time Days

648

Number Of Sites

1

Number Of Participants

2

Portugal

Earliest CTIS Part Ii Submission Date

12-09-2024

Latest Decision Or Authorization Date

12-01-2026

Processing Time Days

487

Number Of Sites

1

Number Of Participants

4

Denmark

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

09-01-2026

Processing Time Days

661

Number Of Sites

1

Number Of Participants

2

Italy

Earliest CTIS Part Ii Submission Date

11-03-2024

Latest Decision Or Authorization Date

16-03-2026

Processing Time Days

735

Number Of Sites

1

Number Of Participants

2

Primary sponsor

Full Name

Ascendis Pharma Growth Disorders A/S

Organisation Type

Pharmaceutical company

Country Of Registered Address

Denmark

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

Code: 4

Name

Celerion Switzerland AG

Responsibilities

Pharmacokinetic Analysis

Name

4G Clinical B.V.

Responsibilities

IRT and data management

Name

Bioclinica Inc.

Responsibilities

Medical image analysis/ review - X-ray, MRI, ultrasound, etc.

Third parties

• {"country":"United Kingdom","full_name":"Atom International Limited","duties_or_roles":"Anthropometrics measurements review and guidance on equipment for anthropometric measurements","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"Offshore lead","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"LKF Laboratorium fuer Klinische Forschung GmbH","duties_or_roles":"Study supplies / Anxillary supplies procurement and distribution","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Netherlands","full_name":"Propharma Group The Netherlands B.V.","duties_or_roles":"Codes: 1, 12","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"BioAgilytix Europe GmbH","duties_or_roles":"Immunogenicity assessments","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"Immunogenicity assessments","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Celerion Switzerland AG","duties_or_roles":"Pharmacokinetic Analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Medical image analysis/ review - X-ray, MRI, ultrasound, etc.","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Netherlands","full_name":"4G Clinical B.V.","duties_or_roles":"IRT and data management","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"ECG","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Participant Travel and Accommodation","organisation_type":"Hospital/Clinic/Other health care facility"}