A Multicenter, Randomized, Operationally Seamless Phase 2/3 Study to Evaluate the Efficacy and Safety of BMN 333 Versus Vosoritide in Children With Achondroplasia
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 160
- 试验地点
- 27
- 主要终点
- Phase 3: Annualized Growth Velocity (AGV) at Week 52
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Phase 3: BMN 333 at selected dose after Phase 2
干预措施: BMN 333 (Drug)
Phase 2: Low Dose
Participants will be randomized to receive different dose levels of BMN 333
干预措施: BMN 333 (Drug)
Phase 3: Vosoritide
weight band dosing, Modified recombinant human C-type natriuretic peptide Vosoritide
干预措施: Vosoritide Injection [Voxzogo] (Drug)
Phase 2: Medium Dose
Participants will be randomized to receive different dose levels of BMN 333
干预措施: BMN 333 (Drug)
Phase 2: High Dose
Participants will be randomized to receive different dose levels of BMN 333
干预措施: BMN 333 (Drug)
Phase 2: Vosoritide
weight band dosing, Modified recombinant human C-type natriuretic peptide Vosoritide
干预措施: Vosoritide Injection [Voxzogo] (Drug)
结局指标
主要结局
Phase 3: Annualized Growth Velocity (AGV) at Week 52
时间窗: 52 weeks
Phase 2: Predicted Annualized Growth Velocity (AGV) at Week 52 (based on AGV at Weeks 26, 39, and 52 [available cumulative data]
时间窗: 52 weeks
次要结局
- Phase 2: AGV at Weeks 26 and 52(26 and 52 weeks)
- Phase 2: Maximum concentration (Cmax) of released vosoritide in plasma(52 weeks)
- Phase 2: Time to reach maximum concentration (Tmax) for BMN 333(52 weeks)
- Phase 2: Time to reach maximum concentration (Tmax) for released vosoritide(52 weeks)
- Phase 2: Change from Baseline in standing height(26 and 52 weeks)
- Phase 2: Change from Baseline in height Z-score(26 and 52 weeks)
- Phase 2: Change from Baseline in upper to lower body segment ratio(26 and 52 weeks)
- Phase 2: Incidence of adverse events (AEs)(52 weeks)
- Phase 2: Incidence of serious adverse events (SAEs)(52 weeks)
- Phase 2: Incidence of events of interest (EOIs)(52 weeks)
- Phase 2: Maximum concentration (Cmax) of BMN 333 in plasma(52 weeks)
- Phase 2: Lowest concentration (C trough) of BMN 333 in plasma(52 weeks)
- Phase 2: Lowest concentration (C trough) of released vosoritide in plasma(52 weeks)
- Phase 3: Change from Baseline in standing height(52 weeks)
- Phase 3: Change from Baseline in height Z-score(52 weeks)
- Phase 3: Change from Baseline in upper to lower body segment ratio(52 weeks)