A Study of Vosoritide in Children With Noonan Syndrome With Inadequate Growth During or After Human Growth Hormone Treatment

Официальное название

A Phase 2, Randomized, Multicenter, Study of Vosoritide in Children With Noonan Syndrome With Inadequate Growth During or After Human Growth Hormone Treatment

Обзор

The purpose of this study in children with Noonan syndrome is to evaluate the effect of 3 doses of vosoritide 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.

Подробное описание

This is a Phase 2, randomized, multicenter, study of vosoritide in children with Noonan syndrome who have inadequate growth during or after human growth hormone (hGH) treatment. The study is intended to characterize the short-term efficacy and safety of 3 dosing regimens of vosoritide. The efficacy and safety of the vosoritide therapeutic dose will be further evaluated, and an analysis of the impact of vosoritide on final adult height (FAH).

Вмешательства

• Препарат Vosoritide Injection
  Modified recombinant human C-type natriuretic peptide Vosoritide

Первичные конечные точки

• Change from baseline in Annualized Growth Velocity (AGV) [Срок оценки: At 6 months]

Вторичные конечные точки (12)

• Incidence of treatment-emergent adverse events [Срок оценки: Until the end of the study, up to 15 years]
• Incidence of new diagnosis of hypertrophic cardiomyopathy in children with Noonan syndrome [Срок оценки: Every 12 months through the end of the study, up to 15 years]
• Incidence of cardiac conditions requiring discontinuation of study treatment [Срок оценки: Every 12 months through the end of the study, up to 15 years]
• Change from baseline in height [Срок оценки: Every 6 months through the end of the study, up to 15 years]
• Change from baseline in height Z-score [Срок оценки: Every 6 months through the end of the study, up to 15 years]
• Change from baseline in 12-month interval AGV [Срок оценки: Until the end of the study, up to 15 years]
• Change from baseline in upper to lower body segment ratio [Срок оценки: Until the end of the study, up to 15 years]
• Change from baseline in arm span to height ratio [Срок оценки: Until the end of the study, up to 15 years]
• Change from baseline in height up to Final Adult Height (FAH) [Срок оценки: Every 6 months through the end of the study, up to 15 years]
• Change from baseline in height Z-score up to FAH [Срок оценки: Every 6 months through the end of the study, up to 15 years]
• 12-month interval AGV summarized by age and sex up to FAH [Срок оценки: Every 12 months through the end of the study, up to 15 years]
• Tanner stage over the course of the study [Срок оценки: Every 6 months through the end of the study, up to 15 years]

Критерии участия

Критерии включения

• Participants must be ≥ 3 years old, and < 11 years old (females) or < 12 years old (males), at the time of signing the informed consent form
• A genetically confirmed diagnosis of Turner syndrome, SHOX deficiency or Noonan syndrome.
• A height assessment corresponding to a height Z-score of ≤ -1.28 SDs (below the 10th percentile for height) in reference to the general population of the same age and sex.
• Tanner Stage 1, at time of signing the ICF.
• Previous or current hGH treatment for short stature associated with their condition.
• Inadequate growth confirmed with an AGV that is less than age- and sex-matched average stature AGV determined using median heights from CDC growth charts

Критерии исключения

• Participants with Turner syndrome known to have Y-chromosome material unless they have undergone gonadectomy and have fully external female genitalia.
• 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.
• Bone age advanced beyond chronological age by more than 2 years.
• Uncorrected congenital heart disease which places the participant at increased risk of an adverse cardiac outcome in the setting of hypotension,
• Have an unstable condition likely to require surgical intervention during the study.
• 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.
• Previous limb-lengthening surgery, or planned or expected to have limb lengthening surgery during the study period.
• Planned or expected bone-related surgery (ie, surgery involving disruption of bone cortex, excluding tooth extraction), during the study period.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 22 центра

• Childrens Hospital Los Angeles — Los Angeles
• Children's Hospital of Orange County Main Campus - Orange — Orange
• Children's Hospital Colorado — Aurora
• Nemours Children's Hospital, Delaware (Alfred I. Dupont Hospital for Children) — Wilmington
• Children's National Medical Center — Washington D.C.
• Nicklaus Children's Hospital — Miami
• Emory University School of Medicine — Atlanta
• St. Luke's Children's Endocrinology and Diabetes — Boise
• … и ещё 14 центров

Франция · 5 центров

• Hôpital de la Timone — Marseille
• Angers University Hospital Center — Angers
• CHU de Toulouse - Hôpital des Enfants — Toulouse
• South Paris University Hospitals - Bicetre Hospital — Le Kremlin-Bicêtre
• Hôpital Robert-Debré — Paris

Австралия · 3 центра

• Royal North Shore Hospital — Saint Leonards
• Childrens Health Queensland Hospital and Health Service — South Brisbane
• Murdoch Children's Research Institute — Parkville

Италия · 3 центра

• Azienda Ospedaliero Universitaria - Ospedale Pediatrico Meyer — Florence
• IRCCS Istituto Giannina Gaslini — Genova
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Roma

Канада · 1 центр

• M.A.G.I.C. Clinic — Calgary

Германия · 1 центр

• Universitätsklinikum des Saarlandes — Homburg

Испания · 1 центр

• Central University Hospital of Asturias — Oviedo

Идентификаторы

NCT: NCT06668805 · 111-211

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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