Study to Evaluate the Efficacy and Safety of BMN 333 Versus Vosoritide in Children With Achondroplasia

Официальное название

A Multicenter, Randomized, Operationally Seamless Phase 2/3 Study to Evaluate the Efficacy and Safety of BMN 333 Versus Vosoritide in Children With Achondroplasia

Обзор

This is a multicenter, multinational, randomized, active-controlled, operationally seamless Phase 2/3 study of BMN 333 in treatment-naïve pediatric participants with achondroplasia (ACH). The study consists of a Phase 2 part and a Phase 3 part.

Подробное описание

The main purpose of this study is to evaluate the effects of BMN 333 on growth compared with vosoritide in participants with achondroplasia who have not received any growth-promoting treatments. The study includes 2 parts: the Phase 2 part will select the optimal BMN 333 dose to be used in Phase 3 and determine study continuation into Phase 3; the Phase 3 part will compare the effects of the selected dose of BMN 333 with vosoritide. Study details for either Phase 2 or Phase 3 include the following:

* Study duration: up to 61 weeks (from screening to Safety Follow-up visit) * Treatment duration: 52 weeks. Treatment frequency: BMN 333, once weekly; vosoritide, once daily

Вмешательства

• Препарат BMN 333
  Administration: Weekly subcutaneous injection
• Препарат Vosoritide Injection [Voxzogo]
  Administration: Daily subcutaneous injection

Первичные конечные точки

• Phase 2: Predicted Annualized Growth Velocity (AGV) at Week 52 (based on AGV at Weeks 26, 39, and 52 [available cumulative data] [Срок оценки: 52 weeks]
• Phase 3: Annualized Growth Velocity (AGV) at Week 52 [Срок оценки: 52 weeks]

Вторичные конечные точки (12)

• Phase 2: AGV at Weeks 26 and 52 [Срок оценки: 26 and 52 weeks]
• Phase 2: Change from Baseline in standing height [Срок оценки: 26 and 52 weeks]
• Phase 2: Change from Baseline in height Z-score [Срок оценки: 26 and 52 weeks]
• Phase 2: Change from Baseline in upper to lower body segment ratio [Срок оценки: 26 and 52 weeks]
• Phase 2: Incidence of adverse events (AEs) [Срок оценки: 52 weeks]
• Phase 2: Incidence of serious adverse events (SAEs) [Срок оценки: 52 weeks]
• Phase 2: Incidence of events of interest (EOIs) [Срок оценки: 52 weeks]
• Phase 2: Maximum concentration (Cmax) of BMN 333 in plasma [Срок оценки: 52 weeks]
• Phase 2: Maximum concentration (Cmax) of released vosoritide in plasma [Срок оценки: 52 weeks]
• Phase 2: Time to reach maximum concentration (Tmax) for BMN 333 [Срок оценки: 52 weeks]
• Phase 2: Time to reach maximum concentration (Tmax) for released vosoritide [Срок оценки: 52 weeks]
• Phase 2: Lowest concentration (C trough) of BMN 333 in plasma [Срок оценки: 52 weeks]

Критерии участия

Критерии включения

• Participants must be aged ≥ 2 to < 11 years (Phase 2) or ≥ 2 to < 18 years (Phase 3), at the time of signing the informed consent
• Participants must have ACH (confirmed by documented genetic testing) and open epiphyses
• Are Tanner Stage I (Phase 2) or any Tanner stage (Phase 3)
• Are ambulatory and able to stand without assistance

Критерии исключения

• Have any short stature condition other than ACH (eg, hypochondroplasia, trisomy 21, pseudoachondroplasia, GH deficiency)
• Have any of the following disorders: Hypothyroidism or hyperthyroidism, unless treated with evidence of normalized thyroid-stimulating hormone (TSH) levels, diabetes mellitus, unless considered well-controlled, autoimmune inflammatory disease, inflammatory bowel disease, autonomic neuropathy, anemia defined as hemoglobin < 10 g/dL, vitamin D deficiency, significant hip pathology.
• Have history of any renal insufficiency or cardiac/ cardiovascular disease that places the participant at increased risk of an adverse cardiac outcome in the setting of hypotension.
• Have had bone fractures of the long bones or spine within 6 months prior to screening.
• Have used vosoritide, any other approved product (except GH, as detailed below), investigational product, or investigational medical device for the treatment of ACH or short stature at any time
• Have been treated with GH, insulin-like growth factor 1, or anabolic steroids in the 6 months prior to treatment start

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

Простое слепое

Основная цель

Лечение

Центры проведения

США · 9 центров

• UCSF Benioff Children's Hospital Oakland — Oakland
• Nemours Children's Health — Wilmington
• Ann & Robert H. Lurie Children's Hospital of Chicago — Chicago
• Johns Hopkins Medicine — Baltimore
• Cincinnati Children's Hospital Medical Center — Cincinnati
• Children's Hospital of Philadelphia — Philadelphia
• University of Texas Southwestern Medical Center — Dallas
• Texas Children Hospital, Baylor College of Medicine — Houston
• … и ещё 1 центр

Румыния · 2 центра

• Institutul National de Endocrinologie C.I.Parhon — Bucharest
• Craiova Emergency Clinical County — Craiova

South Korea · 2 центра

• Seoul National University Hospital — Seoul
• Pusan National University Yangsan Hospital — Yangsan

Австралия · 1 центр

• Murdoch Children's Research Institute — Parkville

Канада · 1 центр

• Universite de Montreal - Centre Hospitalier Universitaire Sainte-Justine — Montreal

Италия · 1 центр

• Irccs Ospedale Gaslini Di Genova — Genova

Япония · 1 центр

• Osaka City General Hospital — Osaka

Польша · 1 центр

• Uniwersytecki Szpital Kliniczny im. J. Mikulicza-Radeckiego we Wroclawiu Klinika Pediatrii — Wroclaw

Великобритания · 1 центр

• University Hospitals Bristol NHS Foundation Trust - Bristol Royal Hospital for Children — Bristol

Идентификаторы

NCT: NCT07441876 · 333-301

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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