A Phase 2, Multi-center, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study to Evaluate the Safety and Efficacy of AGA2115 in Adults With Type I, III, or IV Osteogenesis Imperfecta (OI)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 30
- 主要终点
- Percent change from Baseline at Month 12 in lumbar spine BMD
研究概览
简要总结
This study will determine the effect of treatment of AGA2115 in adults with Type I, III, or IV osteogenesis imperfecta versus placebo.
详细描述
This Phase 2 dose-ranging study will evaluate the safety and efficacy of AGA2115 at a range of doses in adults with Type I, III, or IV osteogenesis imperfecta. The study will last 27 months with a 24-month treatment period and a 3-month follow-up period. During the first 12 months of the study, participants will be randomized 1:1:1:1 to receive either placebo or one of three dose levels of AGA2115 doses; treatment assignment will be double-blind. Months 12 to 24 will be open-label, and all participants will receive AGA2115. Participants will attend visits where safety and efficacy parameters will be evaluated.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female adults (aged 18 to 75 years inclusive) with a clinical diagnosis of osteogenesis imperfecta Type I, III, or IV with documented genetic testing confirmation of genetic variations in the COL1A1 or COL1A2 genes
- •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
- •BMD T-score of ≤ -1.0 at the lumbar spine, total hip, or femoral neck
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 or osteomalacia or any skeletal condition (other than OI) leading to long-bone deformities and/or increased risk of fractures
- •Treatment with bisphosphonates within the past 6 months
- •Treatment with teriparatide, abaloparatide, strontium ranelate, or hormone replacement therapy within the past 12 months
- •Treatment with denosumab (or denosumab biosimilars) within the past 2 years
- •Treatment with 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
- •Participation in any clinical study within the past 12 months during which the participant was administered any IP (participant must also agree not to enroll in any other clinical study concurrently in which IP is administered)
研究组 & 干预措施
AGA2115 Dose Regimen 1
Participants that complete the double-blind period receiving AGA2115 Dose 1 from study start to Month 12 will continue to a 12-month open-label period. Participants will then receive AGA2115 Dose 2 for Months 12 to 24.
干预措施: AGA2115 (Drug)
Placebo
Participants that complete the double-blind period receiving placebo from study start to Month 12 will continue to a 12-month open-label period. Participants will receive AGA2115 Dose 3 for Months 12 to 24.
干预措施: Placebo (Other)
AGA2115 Dose Regimen 3
Participants that complete the double-blind period receiving AGA2115 Dose 3 from study start to Month 12 will continue to a 12-month open-label period. Participants will receive the same AGA2115 dose for Months 12 to 24.
干预措施: AGA2115 (Drug)
AGA2115 Dose Regimen 2
Participants that complete the double-blind period receiving AGA2115 Dose 2 from study start to Month 12 will continue to a 12-month open-label period. Participants will be kept on the same AGA2115 dose for Months 12 to 24.
干预措施: AGA2115 (Drug)
结局指标
主要结局
Percent change from Baseline at Month 12 in lumbar spine BMD
时间窗: 12 months
Percent change from Baseline at Month 12 in lumbar spine BMD
时间窗: 12 months
次要结局
- Percent change from Baseline at Month 3 and 6 in lumbar spine, total hip, femoral neck, one-third distal radius, and total body (minus head) BMD(3 and 6 months)
- Percent change from Baseline at Month 12 in total hip, femoral neck, one-third distal radius, and total body (minus head) BMD(12 months)
- Percent change from Baseline at Week 1 and Month 1, 3, 6, 9, and 12 in P1NP and CTX-1(Week 1, Month 1, 3, 6, 9, and 12)
- Percentage of participants with fractures during the double-blind treatment period(up to 12 months)
- Annualized fracture rate for incident fractures occurring during the double-blind treatment period (total, long-bone, vertebral, peripheral)(up to 12 months)