A Pivotal, Parallel-Arm, Phase 3, Open-Label, Active-controlled, Global, Multicenter, Randomized Basket Trial Investigating the Efficacy and Safety of Once-weekly Lonapegsomatropin Compared to Daily Somatropin in Prepubertal Children and Adolescents With Growth Failure or Short Stature Due to Growth Hormone Sufficient Disorders - Turner Syndrome, SHOX Deficiency, Small for Gestational Age, and Idiopathic Short Stature
This basket trial will enroll prepubertal children and adolescents with clinically diagnosed and genetically confirmed (if applicable) TS, SHOX-D, SGA, or ISS between ages of ≥2 and \<18 years with open growth plates. The purpose of the study is to see how well treatment with once-weekly lonapegsomatropin works compared to treatment with daily somatropin. Approximately 186 participants will be distributed equally (1:1), to receive either lonapegsomatropin for 2 years or somatropin for 1 year followed by lonapegsomatropin for 1 year. This trial will be conducted in the United States, France, Germany, Italy, Romania, Spain and South Korea.
• Chronological age between ≥2 and \<18 years, at start of screening.
• Naïve to growth hormone and growth hormone promoting therapies.
• Prepubertal.
• Able to stand without assistance.
• Diagnosis of TS, SHOX-D, SGA, or ISS with impaired growth or short stature, according to the following disease-specific criteria:
• TS or SHOX-D (Léri-Weill dyschondrosteosis):
⁃ Diagnosis confirmed by a genetic test. NOTE: Historical test results are acceptable for proof of diagnosis. For karyotypes, a minimum of 20 cells must be counted.
⁃ Impaired growth or short stature defined as:
• (i.) AHV \<25th percentile over a time span of 6-16 months prior to screening utilizing a historical height properly documented in a health care setting (self-measurement record is not accepted) OR (ii.) Height \<5th percentile for sex and age according to the Centers for Disease Control Growth Charts for the United States
• SGA without catch-up growth:
• c. Birth weight and/or birth length \< -2.0 SDS for gestational age according to the 2006 World Health Organization Child Growth Standards. For infants born premature, the Fenton Preterm Infant Growth Chart (Fenton 2013) should be used.
• d. Impaired growth or short stature defined as: (i.) AHV \<25th percentile over a time span of 6-16 months prior to screening properly documented in a health care setting (self-measurement record is not accepted) OR (ii.) Height \< -2.0 SDS for age and sex according to the 2000 Centers for Disease Control Growth Charts for the United States for children ≥ 3 years or height \< -2.5 SDS for age and sex according to the for children ≥ 2 years and \< 3 years
• ISS:
• e. Height \< -2.25 SDS for sex and age according to the Centers for Disease Control Growth Charts for the United States with no identifiable cause for short stature.
• f. Documented normal GH-IGF-1 axis, defined as either: (i.)IGF-1 SDS \>0 at screening based on central laboratory OR (ii.)Historical documentation of normal peak GH upon stimulation test (as defined by local institution) g. 46,XX chromosome as determined by karyotype or microarray if female. For karyotypes, a minimum of 30 cells must be counted.
• 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.
• Written, signed informed consent provided by parent(s) or legal guardian(s) of the participant. Assent should be signed by participant as required by IRB/HREC/IEC.