临床试验/NCT05067335

NCT05067335已完成3 期

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety and Tolerability of Romosozumab Treatment in Postmenopausal Chinese Women With Osteoporosis

UCB Biopharma SRL31 个研究点分布在 1 个国家实际入组 327 人开始时间: 2021年10月21日最近更新: 2026年9月28日

适应症

干预措施

试验速览

阶段: 3 期
状态: 已完成
发起方: UCB Biopharma SRL
入组人数: 327
试验地点: 31
主要终点: Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine to the End of Double-Blind Period

研究概览研究设计入排标准研究组 & 干预措施方案终点试验结果相关文献研究者研究点记录与标识符相似试验

研究概览

简要总结

The purpose of the study is to evaluate the effect of treatment with romosozumab for 6 months compared with placebo on the percent changes in bone mineral density (BMD) at the lumbar spine, at the total hip and femoral neck in postmenopausal Chinese women with osteoporosis.

研究设计

研究类型: 干预性
分配方式: 随机
干预模型: 平行分组
主要目的: 治疗
盲法: 四盲 (受试者、医护人员、研究者、结局评估者)

入排标准

年龄范围: 55 Years 至 90 Years（Adult, Older Adult）
性别: Female
接受健康志愿者: 否

入选标准

Subject is considered reliable and capable of adhering to the protocol, visit schedule, and medication intake according to the judgment of the investigator
Subject is an ambulatory postmenopausal Chinese women, 55 to 90 years of age (inclusive) at the time of Screening. Postmenopause is defined as no spontaneous vaginal bleeding or spotting for 12 or more consecutive months prior to Screening
Subject has a bone mineral density (BMD) T-score ≤-2.50 at the lumbar spine, total hip, or femoral neck, as assessed by the central imaging vendor at the time of Screening based on DXA scans, and using data for Caucasian women from the National Health and Nutritional Examination Survey (NHANES, 1998)
•
Subject must have at least 1 of following independent risk factors for fracture:
- History of fragility fracture (except hip fracture, a severe vertebral fracture or more than 2 moderate vertebral fractures)
- Parental history of hip fracture
- Low body weight (body mass index ≤19kg/m2)
- Elderly (age ≥ 65 years)
- Current smoker
Subject has at least 2 vertebrae in the L1 to L4 region and at least 1 hip that are evaluable by dual-energy x-ray absorptiometry (DXA), as assessed by the central imaging vendor

排除标准

Subject has a BMD T-score of ≤-3.50 at the total hip or femoral neck, as assessed by the central imaging vendor at the time of Screening based on DXA scans, and using data for Caucasian women from NHANES 1998
Subject has a known history of hip fracture
Subject has any severe (SQ3) or more than 2 moderate (SQ2) vertebral fractures, as assessed by the central imaging vendor based on the lateral spine x-ray at Screening
Subject has a history of myocardial infarction (MI)
Subject has a history of stroke
Subject has a vitamin D insufficiency, defined as 25 (OH) vitamin D levels <20 ng/mL, as assessed by the central laboratory at Screening. Vitamin D repletion will be permitted and the subject may be retested once within the Screening Period
•
Subject has used oral bisphosphonates:
- Any doses received within 3 months prior to randomization
- More than 1 month of cumulative use between 3 and 12 months prior to randomization
- More than 3 years of cumulative use, unless the last dose was received ≥5 years prior to randomization
•
Subject has used intravenous (iv) bisphosphonates:
- zoledronic acid
  - Any doses received within 3 years prior to randomization
  - More than 1 dose received within 5 years prior to randomization
- iv ibandronate, iv pamidronate, or iv alendronate (ALN)
  - Any doses received within 12 months prior to randomization
  - More than 3 years of cumulative use, unless the last dose was received ≥5 years prior to randomization
•
Subject has used denosumab or any cathepsin K inhibitor:
- Any doses received within 18 months prior to randomization
•
Subject has used tibolone, cinacalcet, or calcitonin:
- Any doses received within 3 months prior to randomization
•
Subject has used teriparatide (TPTD) or any parathyroid hormone (PTH) derivative:
- Any doses received within 3 months prior to randomization
- More than 1 month of cumulative use between 3 and 12 months prior to randomization
•
Subject has used systemic oral or transdermal estrogen or selective estrogen receptor modulators (SERMs):
- More than 1 month of cumulative use within 6 months prior to randomization
•
Subject has used strontium ranelate or fluoride:
- More than 1 month of cumulative use within 5 years prior to randomization
•
Subject has used hormonal ablation therapy:
- More than 1 month of cumulative use within 6 months prior to randomization
•
Subject has used systemic glucocorticosteroids:
- ≥5mg prednisone equivalent per day for more than 14 days within 3 months prior to randomization
Subject has a history of osteonecrosis of the jaw (ONJ) or atypical femoral fracture (AFF)
•
Subject has evidence of any of the following:
- Current, uncontrolled hyper- or hypothyroidism. Uncontrolled hyperthyroidism is defined as thyroid-stimulating hormone (TSH) and thyroxine (T4) outside of the normal range. Uncontrolled hypothyroidism is defined as TSH >10
- Current, uncontrolled hyperparathyroidism or history of hypoparathyroidism. Uncontrolled hyperparathyroidism is defined as PTH outside the normal range in subjects with concurrent hypercalcemia or PTH values >20 % above upper limit of normal (ULN) in normocalcemic subjects
- Current hypercalcemia or hypocalcemia, defined as albumin-adjusted serum calcium outside the normal range, as assessed by the central laboratory at the time of Screening. Albumin-adjusted serum calcium levels may be retested once in case of an elevated albumin-adjusted serum calcium level within 1.1xULN of the laboratory's reference ranges
- Subject has ≥3xULN of any of the following: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or >ULN total bilirubin (≥1.5xULN total bilirubin if known Gilbert's syndrome). If subject has elevations only in total bilirubin that are >ULN and <1.5xULN, fractionate bilirubin to identify possible undiagnosed Gilbert's syndrome (ie, direct bilirubin <35 %)

研究组 & 干预措施

Placebo

Placebo Comparator

Subjects randomized to this arm will receive placebo during the Double-Blind-Placebo controlled Period and romosozumab during the Open-Label treatment Period

干预措施: Romosozumab (Drug)

Placebo

Placebo Comparator

Subjects randomized to this arm will receive placebo during the Double-Blind-Placebo controlled Period and romosozumab during the Open-Label treatment Period

干预措施: Placebo (Drug)

Romosozumab

Experimental

Subjects randomized to this arm will receive romosozumab during all treatment Periods.

干预措施: Romosozumab (Drug)

方案终点

主要结局

Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine to the End of Double-Blind Period

时间窗: From Baseline (Day 1) to the end of the Double-blind Period (Month 6)

Percent change from baseline in BMD at the lumbar spine was assessed by dual-energy x-ray absorptiometry (DXA) at 6 months. Missing postbaseline BMD other than due to COVID-19 were imputed using the last observation carried forward (LOCF) approach. Missing or out of window (exceed 70 days since previous IMP) post-baseline DXA BMD due to COVID-19 were set to missing and imputed by multiple imputation under missing at random approach. LSM = least square mean.

Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) During the Double-Blind Period

时间窗: From Baseline to the end of the Double-blind Period (Month 6)

An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a IMP, whether or not related to the IMP. TEAEs are defined as all AEs started on or worsened in severity on or after the date of receiving first dose of IMP and before or on the end of study (EOS) date.

Percentage of Participants With Treatment-emergent Adverse Events for Romosozumab During Overall Period

时间窗: From Month 7 up to Month 12 (Placebo/Romo) and From Day 1 up to Month 12 (Romo/Romo) + 3-month SFU (up to Month 15)

An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with use of a IMP, whether or not related to IMP. TEAEs are defined as all AEs started on or worsened in severity on or after date of receiving first dose of IMP and before or on EOS date except lipid-type AEs starting on date of first dose of IMP and not worsening (and not deemed IMP related by the investigator). As pre-specified in Protocol and SAP, TEAEs were assessed and reported for 6 months for participants in placebo/romosozumab arm (Open-label Period) and for a total of 12 months for participants in romosozumab/romosozumab arm (Double-blind Period + Open-label Period combined) + 3 months of Safety follow-up for both arms (Up to Month 15) during overall period.

次要结局

Percent Change From Baseline in Bone Mineral Density at the Total Hip to the End of Double-Blind Period(From Baseline to the end of the Double-blind Period (Month 6))
Percent Change From Baseline in Bone Mineral Density at the Femoral Neck to the End of the Double-Blind Period(From Baseline to the end of the Double-blind Period (Month 6))
Percent Change From Baseline in Bone Mineral Density at the Lumbar Spine at Month 12(Baseline, Month 12)
Percent Change From Baseline in Bone Mineral Density at the Total Hip at Month 12(Baseline, Month 12)
Percent Change From Baseline in Bone Mineral Density at the Femoral Neck at Month 12(Baseline, Month 12)

试验结果

结果已于 2024-12-05 在 ClinicalTrials.gov 公示。在 ClinicalTrials.gov 查看

受试者流程

入组 327 人 · 完成 292 人

主要终点

Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine to the End of Double-Blind Period

percent change · Standard Error · 时间窗: From Baseline (Day 1) to the end of the Double-blind Period (Month 6)

Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine to the End of Double-Blind Period
Placebo （n=104）	Romosozumab （n=214）
0.44 (0.442)	9.81 (0.323)

The Full Analysis Set (FAS) consisted of all randomized study participants who received at least 1 dose of investigational medicinal product (IMP) and provided at least 1 Baseline and post-Baseline BMD measurement.

Difference in LSM(Romosozumab - Placebo) 9.37 · 95% 置信区间 8.34–10.39 · p = <0.001 · ANCOVA

Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) During the Double-Blind Period

percentage of participants · 时间窗: From Baseline to the end of the Double-blind Period (Month 6)

Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) During the Double-Blind Period
Placebo （n=109）	Romosozumab （n=218）
70.6	72.9

The Safety Set (SS) consisted of all randomized study participants who received at least 1 dose of IMP.

Percentage of Participants With Treatment-emergent Adverse Events for Romosozumab During Overall Period

percentage of participants · 时间窗: From Month 7 up to Month 12 (Placebo/Romo) and From Day 1 up to Month 12 (Romo/Romo) + 3-month SFU (up to Month 15)

Percentage of Participants With Treatment-emergent Adverse Events for Romosozumab During Overall Period
Placebo/Romosozumab （n=98）	Romosozumab/Romosozumab Overall （n=218）
80.6	88.1

The SS consisted of all randomized study participants who received at least 1 dose of IMP. The SS for open label period consisted of all randomized study participants who received at least 1 dose of IMP during open label period.

其他终点（5）

Percent Change From Baseline in Bone Mineral Density at the Total Hip to the End of Double-Blind Period

percent change · Standard Error · 时间窗: From Baseline to the end of the Double-blind Period (Month 6)

Percent Change From Baseline in Bone Mineral Density at the Total Hip to the End of Double-Blind Period
Placebo （n=104）	Romosozumab （n=214）
0.07 (0.285)	2.93 (0.206)