A Phase 2b, Multicentre, Multinational, Double-blind, Dose-finding Study, Incorporating an Open Label Substudy, in Adult Patients With Type I, III or IV Osteogenesis Imperfecta Treated With Setrusumab (BPS804)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 112
- 试验地点
- 1
- 主要终点
- Change From Baseline in Radial Trabecular Volumetric Bone Mineral Density (Tr vBMD) at Month 12
研究概览
简要总结
The purpose of this study is to select a suitable dose of BPS804 by measuring the strength/quality of bone using a special type of CT scanner. Participants will be treated for 12 months and followed up for a further 12 months.
详细描述
This study was previously posted by Mereo Biopharma and was transferred to Ultragenyx in February 2021.
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)
盲法说明
Sponsor will be masked until the primary analysis of the study except for open-label substudy treatment arm. The study site pharmacist will be unmasked to treatment allocation throughout. Study treatment will be monitored by a separate unmasked monitoring team.
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
- •Patients with a clinical diagnosis of OI Type I, III or IV with a confirmed defect in the COL1A1/COL1A2 genes, as confirmed by genetic testing
- •One or more fractures in the past 5 years
- •Capable of giving signed consent
排除标准
- •History of skeletal malignancies or other bone diseases (other than OI)
- •History of neural foraminal stenosis (except if due to scoliosis)
- •History of myocardial infarction, angina pectoris, ischaemic stroke or transient ischaemic attack
- •History of endocrine or thyroid/parathyroid conditions that could affect bone metabolism
- •Treatment with bisphosphonates within 3 months of randomisation
- •Treatment with teraparatide, denosumab or other anabolic/anti-reabsorptive medications within 6 months of randomisation
研究组 & 干预措施
Setrusumab 20 mg/kg (Open-Label)
Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules.
干预措施: Vitamin D (Dietary Supplement)
Setrusumab 20 mg/kg (Open-Label)
Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules.
干预措施: zoledronic acid (optional) (Drug)
Setrusumab 2 mg/kg (Blinded)
Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules.
干预措施: zoledronic acid (optional) (Drug)
Setrusumab 8 mg/kg (Blinded)
Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules.
干预措施: zoledronic acid (optional) (Drug)
Setrusumab 20 mg/kg (Blinded)
Setrusumab 20 mg/kg intravenous (IV) infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules.
干预措施: zoledronic acid (optional) (Drug)
Setrusumab 20 mg/kg (Blinded)
Setrusumab 20 mg/kg intravenous (IV) infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules.
干预措施: setrusumab (Drug)
Setrusumab 8 mg/kg (Blinded)
Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules.
干预措施: setrusumab (Drug)
Setrusumab 2 mg/kg (Blinded)
Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules.
干预措施: setrusumab (Drug)
Placebo
Placebo IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules.
干预措施: Vitamin D (Dietary Supplement)
Placebo
Placebo IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules.
干预措施: Calcium (Dietary Supplement)
Setrusumab 20 mg/kg (Open-Label)
Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules.
干预措施: Calcium (Dietary Supplement)
Setrusumab 20 mg/kg (Open-Label)
Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules.
干预措施: setrusumab (Drug)
Setrusumab 2 mg/kg (Blinded)
Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules.
干预措施: Vitamin D (Dietary Supplement)
Setrusumab 2 mg/kg (Blinded)
Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules.
干预措施: Calcium (Dietary Supplement)
Setrusumab 8 mg/kg (Blinded)
Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules.
干预措施: Vitamin D (Dietary Supplement)
Setrusumab 8 mg/kg (Blinded)
Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules.
干预措施: Calcium (Dietary Supplement)
Setrusumab 20 mg/kg (Blinded)
Setrusumab 20 mg/kg intravenous (IV) infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules.
干预措施: Vitamin D (Dietary Supplement)
Setrusumab 20 mg/kg (Blinded)
Setrusumab 20 mg/kg intravenous (IV) infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules.
干预措施: Calcium (Dietary Supplement)
结局指标
主要结局
Change From Baseline in Radial Trabecular Volumetric Bone Mineral Density (Tr vBMD) at Month 12
时间窗: Baseline, Month 12 (end of treatment [EOT])
Assessed by high resolution peripheral quantitative computed tomography (HRpQCT). HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presents the ratio of the means between the visit and Baseline from analysis of covariance (ANCOVA).
Change From Baseline in Radial Bone Strength (Failure Load) at Month 12
时间窗: Baseline, Month 12 (EOT)
Assessed by finite element analysis (FEA) of models generated from HRpQCT images of the distal radius.
Change From Baseline in Radial Bone Strength (Stiffness) at Month 12
时间窗: Baseline, Month 12 (EOT)
Assessed by FEA of models generated from HRpQCT images of the distal radius.
次要结局
- Change From Baseline in OIQoL-A Activity Subscale Score at Months 6 and 12(Baseline, Months 6, 12 (EOT))
- Changes From Baseline in Radial and Tibial Tr VBMD at Months 6 and 12: Open-Label Arm(Baseline, Months 6, 12 (EOT))
- Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set(Baseline, Months 6, 12 (EOT), 18, 24)
- Percentage of Participants With at Least 1 New Fracture (Peripheral, Vertebral, Long-Bone, Any) at Month 12(Month 12 (EOT))
- Change From Baseline in Lumbar, Total Body, and Femoral Neck Bone Mineral Density (BMD) T-score at Month 6(Baseline, Month 6)
- Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time(Baseline, Months 6, 12 (EOT), 18, and 24)
- Change From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12(Baseline, Months 1, 3, 6, 9, 12 (EOT))
- Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set(Baseline, Months 6, 12 (EOT), 18, 24)
- Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) at Months 6 and 12: Open-Label Arm(Baseline, Months 6, 12 (EOT))
- Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD T-score at Month 12(Baseline, Month 12 (EOT))
- Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 12(Baseline, Month 12 (EOT))
- Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set(Baseline, Months 6, 12 (EOT), 18, 24)
- Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) at Months 6 and 12: Open-Label Arm(Baseline, Months 6, 12 (EOT))
- Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set(Baseline, Month 6, Month 12 (EOT))
- Percentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14(up to Month 14)
- Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 6(Baseline, Month 6)
- Change From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12(Baseline, Months 1, 3, 6, 9, 12 (EOT))
- Change From Baseline in SF-12 Mental Component Summary Score at Months 6 and 12(Baseline, Months 6, 12 (EOT))
- Change From Baseline in Osteogenesis Imperfecta Specific Quality of Life Questionnaire for Adults (OIQoL-A) Total Score at Months 6 and 12(Baseline, Months 6, 12 (EOT))
- Change From Baseline in Total vBMD (Radial and Tibial) Over Time(Baseline, Months 6, 12 (EOT), 18, and 24)
- Change From Baseline in Lean and Fat Body Mass From Whole Body at Months 6 and 12(Baseline, Months 6, 12 (EOT))
- Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death(Non-serious AEs: up to Month 14; Serious AEs: up to Month 24. (Average duration of exposure to placebo was 5 months and for setrusumab was 11 month plus follow-up to 24 months.))
- Change From Baseline in Short Form 12 Health Survey (SF-12) Physical Component Summary Score at Months 6 and 12(Baseline, Months 6, 12 (EOT))
- Change From Baseline in Index (Utility) Score on EuroQol 5-Dimension 5-Level Descriptive System (EQ-5D-5L) Score at Months 6 and 12(Baseline, Months 6 and 12 (EOT))
- Change From Baseline in OIQoL-A Pain Subscale Score at Months 6 and 12(Baseline, Months 6, 12 (EOT))