Clinical trial • Phase III • Musculoskeletal

LONAPEGSOMATROPIN for Turner syndrome | Idiopathic short stature | SHOX deficiency | Small for gestational age

Phase III trial of LONAPEGSOMATROPIN for Turner syndrome | Idiopathic short stature | SHOX deficiency | Small for gestational age.

Overview

Trial Therapeutic Area
Musculoskeletal
Trial Disease
Turner syndrome | Idiopathic short stature | SHOX deficiency | Small for gestational age
Trial Stage
Phase III
Drug Modality
Peptide/protein/enzyme
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
29-10-2025
First CTIS Authorization Date
27-02-2026

Trial design

Randomised, open-label, norditropin flexpro (somatropin) — daily somatropin (active comparator; referred to as daily somatropin in title/documentation).-controlled Phase III trial in France, Germany, Italy and others.

Randomised
Yes
Open Label
Yes
Comparator
Norditropin FlexPro (somatropin) — daily somatropin (active comparator; referred to as daily somatropin in title/documentation).
Target Sample Size
120
Trial Duration For Participant
728

Eligibility

Recruits 120 paediatric patients.

Vulnerable Population
Children and adolescents are included (isVulnerablePopulationSelected = true). The trial uses age‑specific assent and consent documents: parent/legal guardian informed consent forms and multiple pediatric assent forms stratified by age (examples in the dataset: assent forms for 'up to 6 yrs', '7-10 yrs', '11-14 yrs', '12-17 yrs', '13 years and older', and 'children up to 8 years'). Scout Clinical standalone consent is available. Documents are provided in multiple languages (French, German, Italian, Romanian, Spanish) as per country-specific SIS/ICF files.

Inclusion criteria

  • {"criterion_text":"- Chronological age between ≥2 and <18 years, at start of screening."}
  • {"criterion_text":"- Naïve to growth hormone and growth hormone promoting therapies."}
  • {"criterion_text":"- Prepubertal."}
  • {"criterion_text":"- Diagnosis of TS, SHOX-D, SGA, or ISS with impaired growth or short stature, according to the following disease-specific criteria: TS or SHOX-D (Léri-Weill dyschondrosteosis) a. Diagnosis confirmed by a genetic test. NOTE: Historical test results are acceptable for proof of diagnosis. For karyotypes, a minimum of 20 cells must be counted. b. Impaired growth or short stature defined as: (i.) AHV <25th percentile over a time span of 6-16 months prior to screening utilizing a historical height properly documented in a health care setting (self-measurement record is not accepted) OR (ii.) Height <5th percentile for sex and age according to the Centers for Disease Control Growth Charts for the United States SGA without catch-up growth c. Birth weight and/or birth length < -2.0 SDS for gestational age according to the 2006 World Health Organization Child Growth Standards. For infants born premature, the Fenton Preterm Infant Growth Chart (Fenton 2013) should be used. d. Impaired growth or short stature defined as: (i.) AHV <25th percentile over a time span of 6-16 months prior to screening properly documented in a health care setting (self-measurement record is not accepted) OR (ii.) Height < -2.0 SDS for age and sex according to the 2000 Centers for Disease Control Growth Charts for the United States for children ≥ 3 years or height < -2.5 SDS for age and sex according to the for children ≥ 2 years and < 3 years ISS e. Height < -2.25 SDS for sex and age according to the Centers for Disease Control Growth Charts for the United States with no identifiable cause for short stature. f. Documented normal GH-IGF-1 axis, defined as either: (i.) IGF-1 SDS >0 at screening based on central laboratory OR (ii.) Historical documentation of normal peak GH upon stimulation test (as defined by local institution) g. 46,XX chromosome as determined by karyotype or microarray if female. For karyotypes, a minimum of 30 cells must be counted."}

Exclusion criteria

  • {"criterion_text":"- Advanced bone age X-ray by central reading defined as >20% above chronological age in months (Greulich 1959)."}
  • {"criterion_text":"- Closed epiphyses as defined as bone age of ≥14.0 years in females or ≥16.0 years in males."}
  • {"criterion_text":"- Exclusion Criteria only applicable to TS: a. Presence of Y chromosome material on genetic testing without history of gonadectomy. b. Less than 10% of 45,X mosaicism. c. Any known, clinically significant, congenital or acquired cardiovascular dysfunction that might interfere with growth."}
  • {"criterion_text":"- Exclusion Criteria only applicable to SGA: a. Any known clinically significant abnormality likely to affect growth or the ability to evaluate growth with standing height measurements: (i.) Chromosomal aneuploidy, significant gene mutations, or medical syndromes with short stature, including but not limited to Turner syndrome, Laron syndrome, Noonan syndrome, Prader-Willi syndrome, abnormal SHOX-1 gene analysis or absence of GH receptors OR (ii) Congenital abnormalities (causing skeletal abnormalities), including but not limited to skeletal dysplasias."}
  • {"criterion_text":"- Exclusion Criteria only applicable to ISS: a. Known history of any condition that causes disproportionate short stature (i.e. skeletal dysplasias), chromosomal aneuploidy, significant gene mutations, or medical syndromes with short stature, including but not limited to Turner syndrome, Laron syndrome, Noonan syndrome, Prader-Willi syndrome, abnormal SHOX-1 gene analysis or absence of GH receptors."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Annualized height velocity (AHV) at Week 52","definition_or_measurement_approach":"Annualized height velocity measured at Week 52 (AHV at Week 52)."}

Secondary endpoints

  • {"endpoint_text":"- AHV (Week 104)","definition_or_measurement_approach":"Annualized height velocity measured at Week 104."}
  • {"endpoint_text":"- Change from baseline in height SDS (CDC-based) (Weeks 52 and 104)","definition_or_measurement_approach":"Change from baseline in height standard deviation score using CDC growth charts evaluated at Weeks 52 and 104."}
  • {"endpoint_text":"- Change from baseline in height SDS (condition specific if applicable) (Weeks 52 and 104)","definition_or_measurement_approach":"Change from baseline in height SDS using condition‑specific references where applicable, assessed at Weeks 52 and 104."}
  • {"endpoint_text":"- Treatment-emergent adverse events (AEs)","definition_or_measurement_approach":"Recording and summarising treatment-emergent adverse events during the study period."}
  • {"endpoint_text":"- Safety labs, vital signs, physical exam, local tolerability assessments, and fundoscopy","definition_or_measurement_approach":"Standard safety assessments including laboratory tests, vital signs, physical examinations, local tolerability checks and fundoscopy evaluations."}
  • {"endpoint_text":"- Bone age (Weeks 52 and 104)","definition_or_measurement_approach":"Bone age assessment at Weeks 52 and 104 (central reading referenced elsewhere)."}
  • {"endpoint_text":"- Bone age:chronological age ratio (Weeks 52 and 104)","definition_or_measurement_approach":"Ratio of bone age to chronological age evaluated at Weeks 52 and 104."}

Recruitment

Registry Or Advocacy Recruitment
True, Groupe D’Etude Des Histiocytoses
Planned Sample Size
120
Recruitment Window Months
36
Consent Approach
Informed consent from parent(s)/legal guardian(s) for minors with multiple age-specific pediatric assent forms used depending on participant age (examples: assent forms for 'up to 6 yrs', '7-10 yrs', '11-14 yrs', '12-17 yrs', '13 years and older', and parent/legal guardian forms). Scout Clinical standalone consent is provided for certain procedures. Subject information and informed consent documents are available in multiple languages per country (French, German, Italian, Romanian, Spanish as evidenced by country-specific SIS/ICF documents).

Methods

  • Distribution of clinician referral cards and patient-facing cards (country-specific K2 recruitment materials; e.g. Germany and Spain documents named 'K2_* Recruitment Material').
  • Site-based recruitment at pediatric endocrinology and university hospital clinics (multiple sites listed per country in trialSites).
  • Country-specific recruitment procedures documented (K1 recruitment procedure documents available for France, Italy, Romania, Germany, Spain).
  • Use of a patient organisation as contact/partner at least in France (site entry for 'Groupe D’Etude Des Histiocytoses').
  • Third-party vendor support for travel, accommodation arrangement and patient reimbursement provided by Scout Clinical (explicit sponsor duty).

Geography

Total Number Of Sites
25
Total Number Of Participants
66

France

Earliest CTIS Part Ii Submission Date
12-12-2025
Latest Decision Or Authorization Date
27-02-2026
Processing Time Days
77
Number Of Sites
3
Number Of Participants
14

Sites

Site Name
Groupe D’Etude Des Histiocytoses
Department Name
Service de Physiologie – Explorations fonctionnelles pédiatriques
Contact Person Name
Muriel HOUANG
Contact Person Email
muriel.houang@aphp.fr
Site Name
Centre Hospitalier Universitaire De Toulouse
Department Name
Endocrinology, Genetics and Medical Gynecology
Contact Person Name
Thomas EDOUARD
Contact Person Email
Edouard.t@chu-toulouse.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Pediatric Endocrinology and Diabetes for Children
Contact Person Name
Agnès LINGLART
Contact Person Email
Agnes.linglart@aphp.fr

Germany

Earliest CTIS Part Ii Submission Date
16-01-2026
Latest Decision Or Authorization Date
04-05-2026
Processing Time Days
108
Number Of Sites
9
Number Of Participants
14

Sites

Site Name
Universitaetsklinikum Erlangen AöR
Department Name
Children and Adolescent Clinic
Contact Person Name
Joachim Wölfle
Contact Person Email
Joachim.Woelfle@uk-erlangen.de
Site Name
Universitaet Des Saarlandes
Department Name
Division of Pediatric Endorcinology and Diabetes
Contact Person Name
Tilman Rohrer
Contact Person Email
tilman.rohrer@uks.eu
Site Name
Otto Von Guericke Universitaet Magdeburg
Department Name
Pediatric Endorcinology and Diabetology
Contact Person Name
Katja Palm
Contact Person Email
Katja.palm@med.ovgu.de
Site Name
Universitaetsklinikum Tuebingen AöR
Department Name
Clinic for Children and Adolescent Medicine
Contact Person Name
Gerhard Binder
Site Name
Medical Center - University Of Freiburg
Department Name
Children and Adolescent Clinic – Pediatric Endorcinology and Diabetology
Contact Person Name
Clemens Kamrath
Site Name
Hannoversche Kinderheilanstalt
Department Name
Diabetology, endocrinology, gastroenteology and clinical research
Contact Person Name
Felix Reschke
Contact Person Email
Felix.reschke@hka.de
Site Name
Universitaetsklinikum Koeln AöR
Department Name
Clinic and Polyclinic for Pediatrics and Adolescent Medicine
Contact Person Name
Heike Hoyer-Kuhn
Site Name
Universitaetsklinikum Duesseldorf AöR
Department Name
Department of General Pediatrics, Neonatology and Pediatric Cardiology
Contact Person Name
Sebastian Kummer
Site Name
Universitaetsklinikum Augsburg
Department Name
Clinic for Children and Adolescent Medicine
Contact Person Name
Desiree Dunstheimer

Italy

Earliest CTIS Part Ii Submission Date
05-02-2026
Latest Decision Or Authorization Date
02-03-2026
Processing Time Days
25
Number Of Sites
4
Number Of Participants
18

Sites

Site Name
Istituto Di Ricovero E Cura A Carattere Scientifico Materno Infantile Burlo Garofolo
Department Name
Pediatrics Unit
Contact Person Name
Gianluca Tornese
Site Name
Ospedale Pediatrico Bambino Gesu
Department Name
Endocrinology and Diabetes Unit
Contact Person Name
Stefano Cianfarani
Contact Person Email
stefano.cianfarani@uniroma2.it
Site Name
Azienda Ospedaliera Universitaria Federico II Di Napoli
Department Name
Pediatrics Endocrinology
Contact Person Name
Donatella Capalbo
Contact Person Email
donatella.capalbo@unina.it
Site Name
Azienda Ospedaliera Universitaria Universita' Degli Studi Della Campania Luigi Vanvitelli
Department Name
Department of Woman, child, general and specialized surgery
Contact Person Name
Anna Grandone
Contact Person Email
anna.grandone@unicampania.it

Romania

Earliest CTIS Part Ii Submission Date
27-02-2026
Latest Decision Or Authorization Date
09-03-2026
Processing Time Days
10
Number Of Sites
2
Number Of Participants
6

Sites

Site Name
Spitalul Clinic Judetean De Urgenta Sf. Spiridon Iasi
Department Name
Endocrinology
Contact Person Name
Cristina Preda
Contact Person Email
contact@spitalspiridon.ro
Site Name
Spitalul Clinic Judetean Mures
Department Name
Endocrinology
Contact Person Name
Maria Ionela Pascanu

Spain

Earliest CTIS Part Ii Submission Date
05-12-2025
Latest Decision Or Authorization Date
07-05-2026
Processing Time Days
153
Number Of Sites
7
Number Of Participants
14

Sites

Site Name
Hospital Universitario Miguel Servet
Department Name
Pediatric endocrinology
Contact Person Name
Antonio de Arriba Muñoz
Contact Person Email
adearriba@salud.aragon.es
Site Name
Hospital Universitari Vall D Hebron
Department Name
Pediatric endocrinology
Contact Person Name
Maria Clemente Leon
Contact Person Email
maria.clemente@vallhebron.cat
Site Name
Hospital Universitario Regional De Malaga
Department Name
Pediatric endocrinology
Contact Person Name
Isabel Leiva Gea
Contact Person Email
isabeleivag@gmail.com
Site Name
Complexo Hospitalario Universitario De Santiago
Department Name
Pediatric endocrinology
Contact Person Name
Paloma Cabanas
Site Name
Hospital Sant Joan De Deu Barcelona
Department Name
Pediatric endocrinology
Contact Person Name
Silvia Marin del Barrio
Contact Person Email
silvia.marin@sjd.es
Site Name
Hospital Universitario La Paz
Department Name
Pediatric endocrinology
Contact Person Name
Isabel Gonzalez Casado
Contact Person Email
igcasado@salud.madrid.org
Site Name
Hospital Universitario Miguel Servet (additional listing)
Department Name
Pediatric endocrinology
Contact Person Name
Antonio de Arriba Muñoz
Contact Person Email
adearriba@salud.aragon.es

Sponsor

Primary sponsor

Full Name
Ascendis Pharma Endocrinology Division A/S
Organisation Type
Pharmaceutical company
Country Of Registered Address
Denmark

Contract research organisations

Name
Icon (Lr) Limited
Responsibilities
Multiple duties including site platform solutions and other operational activities (codes 1,12,15,5,8 listed in sponsor duties).
Name
Icon Laboratory Services Inc.
Responsibilities
Laboratory services / endocrine laboratory support.
Name
4G Clinical B.V.
Responsibilities
IRT (interactive response technology) management.
Name
Veeva Systems Inc.
Responsibilities
Clinical data management / systems (code 7).
Name
Cognizant Technology Solutions India Private Limited
Responsibilities
Pharmacovigilance vendor activities.

Third parties

  • {"country":"Germany","full_name":"GBA Central Lab Services GmbH","duties_or_roles":"Central PD Lab","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Clario Medical Imaging Inc.","duties_or_roles":"Medical image analysis / Review X-ray","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Icon (Lr) Limited","duties_or_roles":"Codes: 1,12,15 (Site platform solutions),5,8","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Icon Laboratory Services Inc.","duties_or_roles":"Endocrinology","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"Sweden","full_name":"SVAR Life Science AB","duties_or_roles":"Immunogenicity assessments","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Icon (Lr) Limited (alternate address entry)","duties_or_roles":"Code: 4","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"Immunogenicity assessments","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Centogene GmbH","duties_or_roles":"Genetic testing","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Travel / accommodation arrangement and patient reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"Netherlands","full_name":"4G Clinical B.V.","duties_or_roles":"IRT","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Veeva Systems Inc.","duties_or_roles":"Code: 7","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"India","full_name":"Cognizant Technology Solutions India Private Limited","duties_or_roles":"PV vendor","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Celerion Inc.","duties_or_roles":"Pharmacokinetic Analysis","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
Lonapegsomatropin
Active Substance
LONAPEGSOMATROPIN
Modality
Peptide/protein/enzyme
Routes Of Administration
SUBCUTANEOUS
Route
SUBCUTANEOUS
Authorisation Status
prodAuthStatus: 1
Frequency
Once-weekly (per trial title for investigational arm)
Investigational Product Name
Norditropin FlexPro (somatropin)
Active Substance
SOMATROPIN
Modality
Peptide/protein/enzyme
Routes Of Administration
SUBCUTANEOUS
Route
SUBCUTANEOUS
Authorisation Status
prodAuthStatus: 2 (marketing authorisation present, marketingAuthNumber: 45069 in Denmark)
Frequency
Daily (comparator described as daily somatropin)

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