A Phase 2 Multi-center, Randomized, Open-Label, Dose Regimen-Finding Study of AGA2115 in Chinese Adults and Adolescents With Type I, III, or IV Osteogenesis Imperfecta
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 48
- 试验地点
- 4
- 主要终点
- Occurrence of Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
This study is to evaluate the safety and efficacy of AGA2115 at three different dose regimens in Chinese adults and adolescents with Type I, III, or IV Osteogenesis imperfecta (OI).
详细描述
This Phase 2 study will evaluate the safety and efficacy of AGA2115 in three different dosing regimens in Chinese adults and adolescents with Type I, III, or IV OI. Participants will be in the study for 24 or 27 months depending on their assigned cohort. During the first 12 months of the study, adult and adolescent participants will be randomized separately in a 1:1:1:1 ratio to one of three AGA2115 dosing regimens or control cohort. During months 12 to 24 or 27, all participants will receive AGA2115 and attend visits for the evaluation of safety and efficacy parameters.
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
- None
入排标准
- 年龄范围
- 12 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults (18-75 years) or adolescents (12-17 years) with a confirmed diagnosis of Osteogenesis Imperfecta (OI) Type I, III, or IV with genetic confirmation of pathogenic variants in COL1A1 or COL1A2 genes
- •BMD T-score of ≤-1.0 at the lumbar spine, total hip, or femoral neck (adults) or BMD Z-score of ≤-1.0 at the lumbar spine, total hip, or femoral neck (adolescents)
- •Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol
排除标准
- •Vitamin D deficiency
- •Concomitant uncontrolled diseases or conditions that could affect bone metabolism such as hypo-/hyperparathyroidism, hypo-/hyperthyroidism, abnormal thyroid function or thyroid disease, or other endocrine disorders.
- •Current hyper- or hypocalcemia.
- •History of rickets, osteomalacia, or other significant skeletal disorders (excluding OI) leading to long-bone deformities and/or increased risk of fractures.
- •Use of bisphosphonates within the past 6 months.
- •Use of teriparatide, abaloparatide, strontium ranelate, or hormone replacement therapy within the past 12 months.
- •Use of denosumab (or denosumab biosimilars) within the past 2 years.
- •Use of anti-sclerostin antibody medications (romosozumab, setrusumab, blosozumab) at any time.
- •History of myocardial infarction or stroke (or other cardiovascular associated event deemed significant) within the past 12 months.
- •Malignancy within the last 5 years.
- •Pregnant or breastfeeding women, or women planning to become pregnant during the study or within 4 months after the last dose of IP.
研究组 & 干预措施
Cohort 1
Adult participants will receive AGA2115 Dose Regimen 1.
干预措施: AGA2115 (Drug)
Cohort 2
Adult participants will receive AGA2115 Dose Regimen 2.
干预措施: AGA2115 (Drug)
Cohort 3
Adult participants will receive AGA2115 Dose Regimen 3.
干预措施: AGA2115 (Drug)
Cohort 5
Adolescent participants will receive AGA2115 Dose Regimen 1.
干预措施: AGA2115 (Drug)
Cohort 4
Adult participants will only receive AGA2115 Dose Regimen 2 in the second year.
Cohort 8
Adolescent participants will only receive AGA2115 Dose Regimen 2 in the second year.
Cohort 7
Adolescent participants will receive AGA2115 Dose Regimen 3.
干预措施: AGA2115 (Drug)
Cohort 6
Adolescent participants will receive AGA2115 Dose Regimen 2.
干预措施: AGA2115 (Drug)
结局指标
主要结局
Occurrence of Treatment-Emergent Adverse Events (TEAEs)
时间窗: Baseline to Month 27 (Cohorts 1 and 5); Baseline to Month 24 (Cohorts 2, 3, 4, 6, 7 and 8)
次要结局
- Change from Baseline at Month 3, 6, 9, and 12 in BMD Z-score at lumbar spine, total hip, femoral neck, one-third distal radius, and total body (minus head) for adolescents.(Month 3, 6, 9, and 12)
- Percent change from Baseline at Month 3, 6, 9 and 12 in Bone Mineral Density (BMD) at lumbar spine, total hip, femoral neck, one-third distal radius, and total body (minus head) for adults and adolescents.(Months 3, 6, 9, and 12)
- Percent Change from Baseline at Week 1 and Month 1, 3, 6, 9, and 12 in bone turnover markers CTX-1 and P1NP(Week 1, Month 1, 3, 6, 9, and 12)
- Percentage of participants with fractures between Baseline and Month 12(Baseline to Month 12)
- Annualized fracture rate for incident fractures occurring between Baseline and Month 12(Baseline to Month 12)
- AGA2115 observed concentration for the treatment groups(Day 1 to Month 27 (Cohorts 1 and 5); Day 1 to Month 24 (Cohorts 2, 3, 4, 6, 7 and 8).)
- Serum anti-AGA2115 antibodies(Day 1 to Month 27 (Cohorts 1 and 5); Day 1 to Month 24 (Cohorts 2, 3, 4, 6, 7 and 8).)