A Trial to Investigate Different Doses of Lonapegsomatropin Compared to Somatropin in Individuals With Turner Syndrome

New InsiGHTS: A Multicenter, Phase 2, Randomized, Open-label, Active-controlled, Parallel Group Clinical Trial to Investigate the Safety, Tolerability, and Efficacy of Different Dose Levels of Once-weekly Lonapegsomatropin Compared to Daily Somatropin in Prepubertal Individuals With Turner Syndrome

A 104 week dose finding open label trial followed by an optional 78 week open label extension of lonapegsomatropin, a long-acting growth hormone product, administered once-a-week versus daily somatropin product in prepubertal individuals with Turner syndrome. Approximately 48 individuals (12 individuals per arm) will be randomized to receive one of three doses of lonapegsomatropin or a daily injection of somatropin. This is a trial that will be conducted in the United States.

Study Overview

• Status: Active, not recruiting
• Conditions: Turner Syndrome
• Intervention / Treatment: Biological: Lonapegsomatropin; Drug: Somatropin

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Ascendis Pharma Investigational Site
    • San Diego, California, United States, 92123
      • Ascendis Pharma Investigational Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Ascendis Pharma Investigational Site
  • Florida
    • Orlando, Florida, United States, 32827
      • Ascendis Pharma Investigational Site
    • St. Petersburg, Florida, United States, 33701-4804
      • Ascendis Pharma Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Ascendis Pharma Investigational Site
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Ascendis Pharma Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ascendis Pharma Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Ascendis Pharma Investigational Site
  • Minnesota
    • Saint Paul, Minnesota, United States, 55102
      • Ascendis Pharma Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • Ascendis Pharma Investigational Site
  • New York
    • Lake Success, New York, United States, 11042
      • Ascendis Pharma Investigational Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Ascendis Pharma Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Ascendis Pharma Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Ascendis Pharma Investigational Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Ascendis Pharma Investigational Site
  • Texas
    • El Paso, Texas, United States, 79902
      • Ascendis Pharma Investigational Site
    • Fort Worth, Texas, United States, 76104
      • Ascendis Pharma Investigational Site
  • Washington
    • Seattle, Washington, United States, 98105
      • Ascendis Pharma Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 10 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age between 1 and 10 years, inclusive.
2. TS diagnosis via genetic test.
3. Prepubertal status.
4. Naïve to growth hormone therapy or growth hormone secretagogue.

5. Exhibit impaired growth defined by at least one of the following:

   1. AHV< 6 cm/year or <25ᵗʰ percentile over a time span of 6-18 months for children of 2 years and older.
   2. Height (or length for individuals < 2 years old) <10ᵗʰ percentile for sex and age according to the 2000 CDC Growth Charts for the United States.
6. Bone age within normal limits for chronological age, defined as no more than 20% above or below chronological age in months or delayed for chronological age (greater than 20% below chronological age), at screening.
7. Biochemically euthyroid (including when on thyroid hormone supplementation).
8. 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.
9. Fundoscopy at Screening without signs/symptoms of intracranial hypertension or proliferative retinopathy or evidence of any other retinal disease for which growth hormone therapy is contraindicated.
10. Capable of giving signed informed consent. Participants and/or parents or legal guardians of participants must sign an informed consent statement. Assent should be obtained from all participants competent to understand the protocol, per IRB requirements.

Exclusion Criteria:

1. Turner Syndrome with presence of Y-chromosomal material on genetic testing and without a history of gonadectomy.
2. Diagnosis of diabetes mellitus.
3. Known history of clinically relevant conditions that may have an effect on growth, e.g. but not limited to celiac disease, malnutrition, treatment with potential growth-influencing medications for Attention-deficit/ hyperactivity disorder (ADHD), etc.
4. Any known, clinically significant, congenital or acquired cardiac/cardiovascular dysfunction that might interfere with growth as determined by transthoracic echocardiogram.
5. Known history or presence of malignancy.

6. Individuals with history of intracranial tumor or cysts, with evidence of growth within the last 12 months prior to Screening.

   Note - Individuals with a history of intracranial tumor may be eligible if there is no evidence of residual tumor as determined by MRI/CT scan(s) performed within 6 to 12 months prior to screening.

7. Hepatic transaminases (i.e., AST or ALT) above 3 times the upper limit of normal according to the central laboratory at screening.
8. Major medical conditions and/or presence of contraindication to hGH treatment.
9. Abnormal renal function.
10. Clinically relevant systemic illness, acute critical illness, and complications following open heart surgery, abdominal surgery, multiple accidental traumas, acute respiratory failure, or similar conditions within 6 months prior to Screening.
11. Poorly controlled hypertension.
12. Receiving prior or concurrent treatment with any agent that might influence growth or interfere with GH secretion or action such as, but not limited to, non steroidal anabolic agents, sex steroids, etc.
13. Oral/intravenous/intramuscular corticosteroids within 90 days prior to or throughout Screening.
14. Known or suspected hypersensitivity to study intervention(s) or related products.
15. Participation in any other trial involving an investigational compound within 90 days prior to Screening or in parallel to this trial.
16. Any disease or condition that, in the judgement of the investigator, may make the individual unlikely to comply with the protocol or presents undue risk.
17. Female who is pregnant, plans to be pregnant, or is breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lonapegsomatropin at 0.24 mg hGH/kg/week; Lonapegsomatropin at 0.24 mg hGH/kg/week administered once-weekly by subcutaneous injection	Biological: Lonapegsomatropin; Once-weekly subcutaneous injection of Lonapegsomatropin
Experimental: Lonapegsomatropin at 0.30 mg hGH/kg/week; Lonapegsomatropin at 0.30 mg hGH/kg/week administered once-weekly by subcutaneous injection	Biological: Lonapegsomatropin; Once-weekly subcutaneous injection of Lonapegsomatropin
Experimental: Lonapegsomatropin at 0.36 mg hGH/kg/week; Lonapegsomatropin at 0.36 mg hGH/kg/week administered once-weekly by subcutaneous injection	Biological: Lonapegsomatropin; Once-weekly subcutaneous injection of Lonapegsomatropin
Active Comparator: Somatropin at 0.05 mg/kg/day; Somatropin at 0.05 mg/kg/day administered once-daily by subcutaneous injection	Drug: Somatropin; Once-daily subcutaneous injection of Somatropin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Height Velocity (AHV) (cm/year)	Calculated based on the difference between the AHV at 6 months and baseline	26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Height Velocity (AHV) (cm/year)	Calculated based on the difference between the AHVs at 12, 24, 36 and 42 months and baseline	52 weeks, 104 weeks, 156 weeks and 182 weeks
Change from baseline in height standard deviation score (SDS)	Calculated based on the difference between the heights SDS at 6, 12, 24, 36 and 42 months and baseline	26 weeks, 52 weeks, 104 weeks, 156 weeks and 182 weeks
Change from baseline in Bone age (calculated years)	Annual change in bone age measurements as per Gruelich-Pyle method	52 weeks, 104 weeks and 156 weeks
Change from baseline in ratio of bone age/chronological age	Calculated as a ratio	52 weeks, 104 weeks and 156 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin-like growth factor 1 (IGF-1) standard deviation score (SDS)	Via Central Lab analysis	26 weeks, 52 weeks, 104 weeks, 156 weeks and 182 weeks

Collaborators and Investigators

• Sponsor: Ascendis Pharma Endocrinology Division A/S

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2023
• Primary Completion (Actual): October 18, 2024
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: January 10, 2023
• First Submitted That Met QC Criteria: January 10, 2023
• First Posted (Actual): January 19, 2023

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Cardiovascular Diseases; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Heart Diseases; Genetic Diseases, Inborn; Gonadal Disorders; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Disorders of Sex Development; Urogenital Abnormalities; Sex Chromosome Disorders; Chromosome Disorders; Sex Chromosome Disorders of Sex Development; Gonadal Dysgenesis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Turner Syndrome; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Pituitary Hormones; Growth Hormone; Pituitary Hormones, Anterior; Human Growth Hormone; lonapegsomatropin
• Other Study ID Numbers: ASND0034

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No