a phase 2 basket study of vosoritide in children with turner syndrome, shox deficiency and noonan syndrome with an inadequate response to human growth hormone

Conditions: Short Stature Homeobox- Containing Gene SHOX Deficiency; Noonan Syndrome; Turner Syndrome

Summary: the purpose of this basket study in children with turner syndrome, shox deficiency, and noonan syndrome is to evaluate the effect of 3 doses of vosoritide versus hgh on growth as measured by agv after 6 months of treatment. the long-term efficacy and safety of vosoritide at the therapeutic dose will be evaluated up to fah.

this is a phase 2, randomized, active-controlled, multicenter, basket study of vosoritide in children with turner syndrome, short stature homeobox-containing gene (shox) deficiency, or noonan syndrome who have an inadequate response to human growth hormone (hgh) treatment. the study is intended to characterize the short-term efficacy and safety of 3 dosing regimens of vosoritide versus hgh. the efficacy and safety of the vosoritide therapeutic dose will be further evaluated, with a comparison to hgh after 2 years of treatment, and an analysis of the impact of vosoritide on final adult height (fah).

Eligibility criteria:
inclusion criteria: 1. participants must be ≥ 3 years old, and \< 10 years old (females) or \< 11 years old (males),at the time of signing the informed consent form 2. a genetically confirmed diagnosis of turner syndrome, shox deficiency or noonan syndrome. 3. a height assessment corresponding to a height z score of ≤ -2.00 sds in reference to the general population of the same age and sex. 4. tanner stage 1, at time of signing the icf. 5. have been receiving continuous hgh for the treatment of short stature associated with their condition for a minimum of 1 year immediately prior to enrollment. 6. are willing to continue on hgh for the baseline growth phase, and for 2 years post randomization if randomized to the hgh arm. 7. inadequate response to prior hgh treatment. exclusion criteria: 1. participants with turner syndrome known to have y-chromosome material unless they have undergone gonadectomy and have fully external female genitalia. 2. diagnosis of systemic disease or condition that may cause short stature other than turner syndrome, shox deficiency, or noonan syndrome, eg, renal, neoplastic, pulmonary, cardiac, gastrointestinal, immunologic and metabolic disease. 3. bone age advanced beyond chronological age by more than 2 years. 4. congenital heart disease which places the participant at increased risk of an adverse cardiac outcome in the setting of hypotension, 5. have an unstable condition likely to require surgical intervention during the study. 6. evidence of decreased growth velocity (agv \< 1.5 cm/year) as assessed over a period of at least 6 months and growth plate closure assessed using bilateral lower extremity x-rays. 7. previous limb-lengthening surgery, or planned or expected to have limb lengthening surgery during the study period. 8. planned or expected bone-related surgery (ie, surgery involving disruption of bone cortex, excluding tooth extraction), during the study period.

Keywords: short stature musculoskeletal diseases bone diseases developmental endocrine system diseases natriuretic peptide, c-type