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

• ClinicalTrials.gov Identifier: NCT05690386
• Recruitment Status: Active, not recruiting
• First Posted: January 19, 2023
• Last Update Posted: April 30, 2024
• Sponsor: Ascendis Pharma Endocrinology Division A/S
• Information provided by (Responsible Party): Ascendis Pharma A/S ( Ascendis Pharma Endocrinology Division A/S )

Study Description

Brief Summary:

A 104 week dose finding open label trial 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.

Condition or disease	Intervention/treatment	Phase
Turner Syndrome	Biological: Lonapegsomatropin; Drug: Somatropin	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: An open label, parallel group with subjects randomized into 1 of 4 treatment groups (1:1:1:1)
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: February 15, 2023
• Estimated Primary Completion Date: December 2024
• Estimated Study Completion Date: June 2026

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Annualized Height Velocity (AHV) (cm/year) [ Time Frame: 26 weeks ]
   Calculated based on the difference between the AHV at 6 months and baseline

Secondary Outcome Measures :

1. Annualized Height Velocity (AHV) (cm/year) [ Time Frame: 52 weeks and 104 weeks ]
   Calculated based on the difference between the AHVs at 12 and 24 months and baseline
2. Change from baseline in height standard deviation score (SDS) [ Time Frame: 26 weeks, 52 weeks and 104 weeks ]
   Calculated based on the difference between the heights SDS at 6, 12, and 24 months and baseline.
3. Change from baseline in Bone age (calculated years) [ Time Frame: 52 weeks and 104 weeks ]
   Annual change in bone age measurements as per Gruelich-Pyle method
4. Change from baseline in ratio of bone age/chronological age [ Time Frame: 104 weeks ]
   Calculated as a ratio

Other Outcome Measures:

1. Insulin-like growth factor 1 (IGF-1) standard deviation score (SDS) [ Time Frame: 26 weeks, 52 weeks, and 104 weeks ]
   Via Central Lab analysis

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 10 Years (Child)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, California

Ascendis Pharma Investigational Site

Palo Alto, California, United States, 94304

Ascendis Pharma Investigational Site

San Diego, California, United States, 92123

United States, Colorado

Ascendis Pharma Investigational Site

Aurora, Colorado, United States, 80045

United States, Florida

Ascendis Pharma Investigational Site

Orlando, Florida, United States, 32827

Ascendis Pharma Investigational Site

Saint Petersburg, Florida, United States, 33701-4804

United States, Georgia

Ascendis Pharma Investigational Site

Atlanta, Georgia, United States, 30322

United States, Idaho

Ascendis Pharma Investigational Site

Idaho Falls, Idaho, United States, 83404

United States, Illinois

Ascendis Pharma Investigational Site

Chicago, Illinois, United States, 60611

United States, Massachusetts

Ascendis Pharma Investigational Site

Boston, Massachusetts, United States, 02114

United States, Minnesota

Ascendis Pharma Investigational Site

Saint Paul, Minnesota, United States, 55102

United States, Nevada

Ascendis Pharma Investigational Site

Las Vegas, Nevada, United States, 89113

United States, New York

Ascendis Pharma Investigational Site

Lake Success, New York, United States, 11042

United States, North Carolina

Ascendis Pharma Investigational Site

Chapel Hill, North Carolina, United States, 27599

United States, Ohio

Ascendis Pharma Investigational Site

Cincinnati, Ohio, United States, 45229

United States, Oklahoma

Ascendis Pharma Investigational Site

Oklahoma City, Oklahoma, United States, 73104

United States, Oregon

Ascendis Pharma Investigational Site

Portland, Oregon, United States, 97239

United States, Texas

Ascendis Pharma Investigational Site

El Paso, Texas, United States, 79902

Ascendis Pharma Investigational Site

Fort Worth, Texas, United States, 76104

United States, Washington

Ascendis Pharma Investigational Site

Seattle, Washington, United States, 98105

Sponsors and Collaborators

Ascendis Pharma Endocrinology Division A/S

More Information

• Responsible Party: Ascendis Pharma Endocrinology Division A/S
• ClinicalTrials.gov Identifier: NCT05690386
• Other Study ID Numbers: ASND0034
• First Posted: January 19, 2023
• Last Update Posted: April 30, 2024
• Last Verified: April 2024

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Turner Syndrome; Gonadal Dysgenesis; Syndrome; Disease; Pathologic Processes; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Sex Chromosome Disorders of Sex Development; Male Urogenital Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Sex Chromosome Disorders; Chromosome Disorders; Genetic Diseases, Inborn; Gonadal Disorders; Endocrine System Diseases