The Efficacy and Safety of Inpegsomatropin Injection in Children With Turner Syndrome (TS) and Short Stature

Official title

Multicenter, Randomized, Open-Label, Positive-Controlled Phase III Clinical Study to Evaluate the Efficacy and Safety of Inpegsomatropin Injection Versus Givopegsomatropin Solution Injection in the Treatment of Short Stature in Children With Turner Syndrome.

Overview

This is a multicenter, randomized, open-label, positive-controlled phase III confirmatory clinical study. A total of 84 children with short stature due to Turner Syndrome (TS) are planned to be enrolled. Stratified by age and karyotype, subjects will be randomized at a 1:1 ratio to either the test group or the positive control group with continuous treatment for 52 weeks. The study aims to compare the efficacy and safety of Inpegsomatropin-Injection versus Givopegsomatropin Solution Injection in children with TS-related short stature, so as to provide evidence for the new indication application of the investigational drug.

Interventions

• Drug Inpegsomatropin-Injection
  Inpegsomatropin injection, 280 μg/kg/week, s.c., once weekly, for 52 weeks.
• Drug Givopegsomatropin Solution Injection
  Givopegsomatropin Solution Injection, 200 μg/kg/week, s.c., once weekly, for 52 weeks.

Primary outcome measures

• Growth velocity (HV, cm/year). [Time frame: Week 52]

Secondary outcome measures (4)

• Change in height standard deviation score from baseline (△HT SDS) [Time frame: From baseline to all follow-up time points at Week 52]
• Change in height velocity from baseline (△HV) [Time frame: From baseline to all follow-up time points at Week 52]
• Change in insulin-like growth factor 1 standard deviation score from baseline (△IGF-1 SDS) [Time frame: From baseline to all follow-up time points at Week 52]
• Ratio of change in bone age from baseline to change in chronological age from baseline (△BA/△CA) [Time frame: Week 52]

Eligibility criteria

Inclusion criteria

• Prepubertal girls at Tanner stage I, with age ≥ 2 years and < 12 years at the time of informed consent signature.
• With clinical manifestations of Turner syndrome and a confirmed diagnosis of Turner syndrome based on peripheral blood karyotype analysis (karyotype analysis of at least 30 metaphase cells).
• At screening, bone age is delayed relative to chronological age or advanced by no more than 1 year (i.e., bone age - chronological age ≤ 1 year).
• At screening, height is below -2 standard deviations (-2SD) of the mean for age and gender; height reference is shown in Appendix 1.
• No prior systematic pharmacological growth-promoting treatment (continuous use for ≥ 1 month), including but not limited to growth hormone, insulin-like growth factor 1 (IGF-1), etc.
• Thyroid hormone replacement therapy (if applicable) received prior to randomization should be maintained on a stable regimen for at least 4 weeks.
• The legal guardian understands and signs the informed consent form; participants aged ≥ 8 years shall also sign the informed consent form. For participants aged under 8 years who are capable of expressing assent, their assent shall be clearly documented.

Exclusion criteria

• Subjects with closed epiphyses.
• Patients with Turner syndrome carrying Y chromosome or Y-chromosome-derived fragments and without gonadectomy.
• Other types of growth and development abnormalities, including but not limited to growth hormone deficiency (GHD), Noonan syndrome, Prader-Willi syndrome, and growth retardation caused by malnutrition.
• Participation in any other clinical trial within 3 months prior to screening with pharmacological or non-pharmacological intervention received.
• Inhaled glucocorticoids used continuously for more than 2 weeks, or oral/intravenous glucocorticoids used continuously for more than 1 week within 3 months prior to screening.
• Receiving other treatments that may affect growth, including but not limited to methylphenidate, sex hormones, gonadotropin-releasing hormone analogs, aromatase inhibitors, anabolic agents, etc.
• Abnormal liver and renal function at screening (ALT > 2 times the upper limit of normal; Cr > upper limit of normal).
• Subjects with abnormal glucose metabolism, including: a. Diagnosed diabetes mellitus; b. Fasting blood glucose ≥ 6.1 mmol/L on two consecutive measurements; c. Glycated hemoglobin (HbA1c) ≥ 6.5%; d. Impaired glucose tolerance judged by the investigator as unsuitable for participation in this study.
• Presence of chronic infectious diseases judged by the investigator to interfere with study participation, such as chronic hepatitis B.
• Subjects with systemic chronic diseases, such as chronic kidney disease, severe cardiovascular diseases (e.g., aortic dissection, uncontrolled hypertension), psychiatric and psychological disorders.
• Subjects with severe congenital skeletal dysplasia; or those with scoliosis > 20°, significant kyphosis, claudication, or a prior diagnosis of slipped capital femoral epiphysis.
• Subjects with a prior history of intracranial hypertension.
• Subjects with a history of malignant tumor or current active malignant tumor, including intracranial tumors.
• Known hypersensitivity to growth hormone or its excipients.
• Subjects with celiac disease who have not maintained a gluten-free diet within 12 months prior to screening.
• Any other conditions deemed inappropriate for enrollment in this clinical trial by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 51 centers

• Anyang Maternal and Child Health Hospital — Anyang
• Beijing Children's Hospital, Capital Medical University — Beijing
• Capital Institute of Pediatrics, Capital Medical University — Beijing
• Peking Union Medical College Hospital, Chinese Academy of Medical Sciences — Beijing
• Peking University First Hospital — Beijing
• The Second Xiangya Hospital of Central South University — Changsha
• Chengdu Women's and Children's Central Hospital — Chengdu
• Children's Hospital of Chongqing Medical University — Chongqing
• … and 43 more centers

Identifiers

NCT: NCT07614152 · PEGPESEN-4-2-004

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗