Clinical trial NCT05690386: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Turner Syndrome
Lead sponsor: Ascendis Pharma A/S
Sponsor class: INDUSTRY
First posted: 2023-01-19
Enrollment: 48
Sex: FEMALE
Minimum age (years): 1
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: An open label, parallel group with subjects randomized into 1 of 4 treatment groups (1:1:1:1)
Primary purpose: TREATMENT

Brief summary: 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.


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.

Primary outcomes:
measure: Annualized Height Velocity (AHV) (cm/year)
timeFrame: 26 weeks
Secondary outcomes:
measure: Annualized Height Velocity (AHV) (cm/year)
timeFrame: 52 weeks, 104 weeks, 156 weeks and 182 weeks
measure: Change from baseline in height standard deviation score (SDS)
timeFrame: 26 weeks, 52 weeks, 104 weeks, 156 weeks and 182 weeks
measure: Change from baseline in Bone age (calculated years)
timeFrame: 52 weeks, 104 weeks and 156 weeks
measure: Change from baseline in ratio of bone age/chronological age
timeFrame: 52 weeks, 104 weeks and 156 weeks
Other outcomes:
measure: Insulin-like growth factor 1 (IGF-1) standard deviation score (SDS)
timeFrame: 26 weeks, 52 weeks, 104 weeks, 156 weeks and 182 weeks
Locations:
city: Palo Alto
country: United States
facility: Ascendis Pharma Investigational Site
state: California
city: San Diego
country: United States
facility: Ascendis Pharma Investigational Site
state: California
city: Aurora
country: United States
facility: Ascendis Pharma Investigational Site
state: Colorado
city: Orlando
country: United States
facility: Ascendis Pharma Investigational Site
state: Florida
city: Saint Petersburg
country: United States
facility: Ascendis Pharma Investigational Site
state: Florida
city: Atlanta
country: United States
facility: Ascendis Pharma Investigational Site
state: Georgia
city: Idaho Falls
country: United States
facility: Ascendis Pharma Investigational Site
state: Idaho
city: Chicago
country: United States
facility: Ascendis Pharma Investigational Site
state: Illinois
city: Boston
country: United States
facility: Ascendis Pharma Investigational Site
state: Massachusetts
city: Saint Paul
country: United States
facility: Ascendis Pharma Investigational Site
state: Minnesota
city: Las Vegas
country: United States
facility: Ascendis Pharma Investigational Site
state: Nevada
city: Lake Success
country: United States
facility: Ascendis Pharma Investigational Site
state: New York
city: Chapel Hill
country: United States
facility: Ascendis Pharma Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: Ascendis Pharma Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: Ascendis Pharma Investigational Site
state: Oklahoma
city: Portland
country: United States
facility: Ascendis Pharma Investigational Site
state: Oregon
city: El Paso
country: United States
facility: Ascendis Pharma Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: Ascendis Pharma Investigational Site
state: Texas
city: Seattle
country: United States
facility: Ascendis Pharma Investigational Site
state: Washington
Study officials:
References: