A Study of Vosoritide Versus Placebo in Children With Hypochondroplasia Aged 0 to < 36 Months

Официальное название

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Vosoritide in Infants and Young Children With Hypochondroplasia, Aged 0 to < 36 Months

Обзор

The purpose of this study is to evaluate the safety and efficacy of daily administration of vosoritide in participants with HCH aged 0 to \< 36 months over a 52-week period.

Подробное описание

Study 111-212 is a Phase 2, randomized, double-blind, placebo-controlled, multicenter study to assess the safety and efficacy of vosoritide versus placebo in infants and young children with HCH.

Eligible participants with documented HCH confirmed by genetic testing will be randomized in a 1:1 ratio to receive vosoritide or placebo. Participants will receive study treatment daily for 52 weeks by subcutaneous (SC) injection, followed by a 2-week safety follow-up visit. Vosoritide dosing will follow a weight-band regimen.

Вмешательства

• Препарат Vosoritide
  The vosoritide dose administered will be based on the participant's weight and will follow the weight-band dosing regimen approved for ACH
• Препарат Placebo
  Subcutaneous injection of recommended dose of placebo

Первичные конечные точки

• Incidence of treatment-emergent adverse events [Срок оценки: From baseline to end of treatment at 52 weeks]
• Incidence of serious adverse events versus placebo over the course of the study [Срок оценки: From baseline to end of treatment at 52 weeks]
• Changes from baseline in standard clinical laboratory values (hematology, urinalysis, and chemistry) [Срок оценки: At week 26, at week 52]
• Changes from baseline in heart rate [Срок оценки: At week 13, at week 26, at week 39, at week 52]
• Change from baseline in height Z-score [Срок оценки: At week 52]
• Changes from baseline in respiratory rate [Срок оценки: At week 13, at week 26, at week 39, at week 52]
• Changes from baseline in temperature [Срок оценки: At week 13, at week 26, at week 39, at week 52]
• Changes from baseline in blood pressure [Срок оценки: At week 13, at week 26, at week 39, at week 52]

Вторичные конечные точки (12)

• Change in height [Срок оценки: At week 52]
• Cumulative annualized growth velocity (AGV) [Срок оценки: At week 52]
• 6-month interval AGV [Срок оценки: At week 26, at week 52]
• Change from baseline in upper to lower body segment ratio [Срок оценки: At week 52]
• Change from baseline in arm span [Срок оценки: At week 52]
• Change from baseline in total body (less head) bone mineral density (BMD) Z-score [Срок оценки: At week 52]
• Change from baseline in lumbar spine BMD Z-score [Срок оценки: At week 52]
• Change from baseline in total body (less head) bone mineral content (BMC) as measured by DXA [Срок оценки: At week 52]
• Change from baseline in lumbar spine BMC as measured by DXA [Срок оценки: At week 52]
• Area under the plasma vosoritide concentration time-curve from time 0 to infinity (AUC0-∞) [Срок оценки: At week 26, at week 52]
• Area under the plasma vosoritide concentration time-curve from time 0 to the last measurable concentration (AUC0-t) [Срок оценки: At week 26, at week 52]
• Elimination half-life of vosoritide (t½) [Срок оценки: At week 26, at week 52]

Критерии участия

Критерии включения

• Participants must be 0 to < 36 months of age at randomization.
• Participants must have a confirmed genetic diagnosis of HCH (obtained via whole genome sequencing; presence of a FGFR3 pathogenic variant associated with HCH).
• Participants aged 0 to < 12 months must have a height Z-score of ≤ -1.0 SDS andparticipants aged ≥ 12 to < 36 months must have a height Z-score of ≤ -2.0 SDS in reference to the average stature of the same sex and age, as calculated using the Center for Disease Control and Prevention (CDC) growth charts.
• Participant's weight at the Day 1 visit (pre-treatment) must be ≥ 3 kg.

Критерии исключения

• Short stature condition other than HCH (eg, ACH, trisomy 21, pseudoachondroplasia).
• Have an unstable medical condition likely to require surgical intervention during the study period.
• Taking any of the prohibited medications.
• Have been treated with growth hormone, insulin-like growth factor 1 (IGF-1), or anabolic steroids in the 6 months prior to Screening, or long-term treatment (> 3 months) at any time.
• Require any investigational agent prior to completion of study period.
• Have received another investigational product or investigational medical device within 30 days prior to the Screening visit.
• Have used any other investigational product or investigational medical device for the treatment of HCH or short stature at any time.
• Have current malignancy, history of malignancy, or currently under work-up for suspected malignancy.
• Have known hypersensitivity to vosoritide or its excipients.
• Have a condition or circumstance that, in the view of the investigator, places the participant at high risk for poor treatment compliance or for not completing the study.
• Have any concurrent disease or condition that, in the view of the investigator, will interfere with study participation or safety evaluations, for any reason.

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

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 10 центров

• Phoenix Children's Hospital - Thomas Campus (Main) — Phoenix
• Cedars-Sinai Medical Center — Los Angeles
• Benioff Children's Hospital - Oakland — Oakland
• Children's National Medical Center — Washington D.C.
• Ann & Robert H. Lurie Children's Hospital of Chicago — Chicago
• The Johns Hopkins University School of Medicine — Baltimore
• University of Minneasota Masonic Children's Hospital — Minneapolis
• University of Missouri — Columbia
• … и ещё 2 центра

Япония · 5 центров

• Kumamoto University Hospital — Kumamoto
• Osaka Women's and Children's Hospital — Osaka
• Institute of Science Tokyo Hospital — Tokyo
• Nihon University Itabashi Hospital — Tokyo
• Tottori University Hospital — Tottori

Германия · 3 центра

• Uniklinik Köln — Cologne
• Universitätsklinikum des Saarlandes — Homburg
• Universitätskinderklinik Magdeburg — Magdeburg

Австралия · 2 центра

• Children's Health Queensland Hospital and Health Service — South Brisbane
• Royal Children's Hospital Melbourne — Parkville

Франция · 2 центра

• Hôpital Bicêtre — Le Kremlin-Bicêtre
• Hospices Civils de Lyon - Hôpital Femme Mère Enfant — Bron

Италия · 2 центра

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Roma
• IRCCS Istituto Giannina Gaslini — Genova

Великобритания · 2 центра

• Myriad Trials — London
• Great Ormond Street Hospital — London

Идентификаторы

NCT: NCT07126262 · 111-212

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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