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Once-weekly lonapegsomatropin versus daily somatropin for children and adolescents with short stature due to growth-hormone-sufficient conditions

A Pivotal, Parallel-Arm, Phase 3, Open-Label, Active-controlled, Global, Multicenter, Randomized Basket Trial Investigating the Efficacy and Safety of Once-weekly Lonapegsomatropin Compared to Daily Somatropin in Prepubertal Children and Adolescents With Growth Failure or Short Stature Due to Growth Hormone Sufficient Disorders - Turner Syndrome, SHOX Deficiency, Small for Gestational Age, and Idiopathic Short Stature

Phase 3 Interventional Ascendis Pharma A/S · NCT07221851

It will test whether a once-weekly injection of lonapegsomatropin helps children and teens with Turner syndrome, SHOX mutation, small-for-gestational-age, or idiopathic short stature grow as well as or better than daily somatropin.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment186 (estimated)
Ages2 Years to 17 Years
SexAll
SponsorAscendis Pharma A/S Industry-sponsored
Drugs / interventionsradiation
Locations11 sites (Sacramento, California and 10 other locations)
Trial IDNCT07221851 on ClinicalTrials.gov

What this trial studies

This randomized, open-label Phase 3 basket trial enrolls prepubertal children and adolescents aged 2 to <18 years with Turner syndrome, SHOX deficiency, SGA without catch-up growth, or idiopathic short stature who are naive to growth hormone therapy. About 186 participants will be randomized 1:1 to receive either lonapegsomatropin once weekly for two years or daily somatropin for one year followed by lonapegsomatropin for one year. Primary outcomes include annualized height velocity and safety monitoring, with regular visits for growth measurements, adverse event reporting, and laboratory assessments. The trial is conducted at sites in the United States, France, Germany, Italy, Romania, Spain, and South Korea.

Who should consider this trial

Good fit: Prepubertal, growth hormone–naïve children and adolescents aged 2 to <18 years with genetically confirmed Turner syndrome or SHOX deficiency, or clinically defined SGA or idiopathic short stature with open growth plates and documented impaired growth are ideal candidates.

Not a fit: Children already on growth hormone therapy, those who are postpubertal with closed growth plates, or those whose short stature is due to growth hormone deficiency or other non–GH-sufficient causes are unlikely to benefit from this comparison.

Why it matters

Potential benefit: If successful, once-weekly dosing could produce comparable or better growth while reducing injection frequency and improving convenience for patients and families.

How similar studies have performed: Weekly lonapegsomatropin has demonstrated efficacy and safety in pediatric growth hormone deficiency and has regulatory approval for that indication, but its use in Turner, SHOX‑D, SGA, and ISS populations is less well established.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Chronological age between ≥2 and \<18 years, at start of screening.
2. Naïve to growth hormone and growth hormone promoting therapies.
3. Prepubertal.
4. Able to stand without assistance.
5. 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):
   1. 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.
   2. 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.
6. If on hormone replacement therapies for any hormone deficiencies other than growth hormone (e.g., adrenal, thyroid), must be on adequate and stable doses for ≥4 weeks prior to and throughout screening.
7. Written, signed informed consent provided by parent(s) or legal guardian(s) of the participant. Assent should be signed by participant as required by IRB/HREC/IEC.

Exclusion Criteria:

1. Advanced bone age X-ray by central reading defined as \>20% above chronological age in months (Greulich 1959).
2. Closed epiphyses as defined as bone age of ≥14.0 years in females or ≥16.0 years in males.
3. Current clinical diagnosis of diabetic retinopathy
4. Any diagnosis or presence at screening of the following:

   1. Untreated moderate or severe sleep apnea as determined by formal (local) read of an inpatient or at-home sleep study.
   2. Prader Willi syndrome with severe obesity, history of severe upper airway obstruction, or severe respiratory impairment.
5. Signs/symptoms of intracranial hypertension, active proliferative retinopathy.
6. Uncontrolled hypo- or hyperthyroidism.
7. Uncontrolled diabetes mellitus (defined as: HbA1c \>7.5% from central laboratory at screening).
8. Known history or diagnosis of any gastrointestinal inflammatory condition, HIV, radiation exposure, other skeletal dysplasias, growth hormone deficiency, and/or cardio-thoracic surgery due to their independent effects on growth.
9. Any significant hepatic or renal abnormality, such as abnormal renal function (defined as eGFR \<60 mL/min/1.73m2).
10. Undiagnosed or uncontrolled hypertension.
11. Receiving treatment with any agent that might influence growth or interfere with GH secretion or action including any sex steroids and stimulants for attention-deficit/hyperactivity disorder (ADHD).
12. High dose inhaled glucocorticoid for more than 28 consecutive days total over the course of 12 months.
13. Female who is pregnant, plans to be pregnant, or breastfeeding.
14. Participation in another interventional clinical trial involving an investigational compound within 90 days prior to screening or in parallel to this trial.
15. Any disease or condition that, in the judgement of the investigator, may make the participant unlikely to comply with the requirements of the protocol or any condition that presents undue risk from the investigational product or trial procedures.
16. Exclusion Criteria only applicable to TS:

    1. Presence of Y chromosome material on genetic testing without history of gonadectomy.
    2. Less than 10% of 45,X mosaicism.
    3. Any known, clinically significant, congenital or acquired cardiovascular dysfunction that might interfere with growth.
17. 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.

    (ii.)Congenital abnormalities (causing skeletal abnormalities), including but not limited to skeletal dysplasias.
18. Exclusion Criteria only applicable to ISS:

    1. 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.

Where this trial is running

Sacramento, California and 10 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Turner SyndromeShort Stature Homeobox Gene MutationIdiopathic Short StatureSmall for Gestational Age at DeliveryNoonan SyndromeGrowth HormoneShort StatureGrowth Failure
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.