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 )

Tracking Information

• First Submitted Date: January 10, 2023
• First Posted Date: January 19, 2023
• Last Update Posted Date: April 30, 2024
• Actual Study Start Date: February 15, 2023
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 10, 2023)

Annualized Height Velocity (AHV) (cm/year) [ Time Frame: 26 weeks ]

Calculated based on the difference between the AHV at 6 months and baseline

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 10, 2023)

• 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
• 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.
• 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
• Change from baseline in ratio of bone age/chronological age [ Time Frame: 104 weeks ]
  Calculated as a ratio

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: January 10, 2023)

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

Via Central Lab analysis

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: A Trial to Investigate Different Doses of Lonapegsomatropin Compared to Somatropin in Individuals With Turner Syndrome
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

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

• Condition: Turner Syndrome

Intervention

• Biological: Lonapegsomatropin
  Once-weekly subcutaneous injection of Lonapegsomatropin
• Drug: Somatropin
  Once-daily subcutaneous injection of Somatropin

Study Arms

• Experimental: Lonapegsomatropin at 0.24 mg hGH/kg/week
  Lonapegsomatropin at 0.24 mg hGH/kg/week administered once-weekly by subcutaneous injection
  Intervention: Biological: Lonapegsomatropin
• Experimental: Lonapegsomatropin at 0.30 mg hGH/kg/week
  Lonapegsomatropin at 0.30 mg hGH/kg/week administered once-weekly by subcutaneous injection
  Intervention: Biological: Lonapegsomatropin
• Experimental: Lonapegsomatropin at 0.36 mg hGH/kg/week
  Lonapegsomatropin at 0.36 mg hGH/kg/week administered once-weekly by subcutaneous injection
  Intervention: Biological: Lonapegsomatropin
• Active Comparator: Somatropin at 0.05 mg/kg/day
  Somatropin at 0.05 mg/kg/day administered once-daily by subcutaneous injection
  Intervention: Drug: Somatropin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 10, 2023): 48
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2026
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes

• Ages: 1 Year to 10 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05690386
• Other Study ID Numbers: ASND0034
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Ascendis Pharma A/S ( Ascendis Pharma Endocrinology Division A/S )
• Original Responsible Party: Same as current
• Current Study Sponsor: Ascendis Pharma Endocrinology Division A/S
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Ascendis Pharma A/S
• Verification Date: April 2024