A Randomised, Double Blind, Multicentre Phase III Study to Assess the Efficacy and Safety of RGB-14-P Compared to Prolia® in Women With Postmenopausal Osteoporosis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 473
- 试验地点
- 58
- 主要终点
- Percentage Change From Baseline (%CfB) in Lumbar Spine Bone Mineral Density (BMD)
研究概览
简要总结
This study will be conducted to assess the efficacy, pharmacodynamic (PD), safety, tolerability, and immunogenicity of RGB -14- P compared to US-licensed Prolia® in participants with postmenopausal osteoporosis, in a comparative manner.
详细描述
This is a randomized, double-blind, multicentre, multiple fixed-dose, 2-arm parallel-group study that includes 2 periods as:
- Main period (52 weeks), consists of Treatment Period 1 (26 weeks) and Treatment Period 2 (26 weeks). On Day 1 of Treatment Period 1, prior to dosing, participants will be randomized in a 1:1 ratio to receive either RGB-14-P or Prolia®.
- Transition Period: consists of Treatment Period 3 (26 weeks). On Day 1 of Treatment Period 3 (Week 52), a subset of participants who received Prolia® during the Main Period will be re-randomized 1:1 to receive either a dose RGB-14-P or Prolia® in a double-blinded manner. A subset of participants continuing in the Transition Period who received RGB-14-P during the Main Period will continue to receive a dose of RGB-14- P but will also follow the randomization procedure to maintain blinding.
All participants will receive the study drugs on 2 occasions (Weeks 0 and 26), on Day 1 of Treatment Periods 1 and 2. Participants continuing to the Transition Period will receive the study drugs on a third-occasion (Week 52), Day 1 of Treatment Period 3. One Treatment Period will take 6 months (26 weeks, 183 days).
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, Care Provider)
盲法说明
A double-blind design will be used during the main and transition periods.
入排标准
- 年龄范围
- 60 Years 至 90 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Participant is an ambulatory postmenopausal woman, diagnosed with osteoporosis, able to walk, and not bedridden
- •Participant has an absolute BMD consistent with T score ≤ 2.5 and ≥ 4.0 at the lumbar spine as measured by dual-energy X-ray absorptiometry (DXA) during the Screening Period and at least 2 lumbar vertebrae (from L1 to L4) must be evaluable by DXA
- •Participant has body weight ≥ 50 and ≤ 90 kg at the Screening Period
- •Participants must meet the following criteria to be enrolled in the Transition Period:
- •Have been enrolled, received both doses of the test drug, and completed the scheduled Main Period (up to Week 52) of the RGB-14-101 study
排除标准
- •Participant has a history and/or presence of a severe or more than two moderate vertebral fractures as determined by central reading of lateral spine X-ray during the Screening Period
- •Participant has a history and/or presence of hip fracture
- •Participant has a history and/or presence of atypical femur fracture
- •Participant presents with an active healing fracture
- •Participant has a bilateral hip replacement (unilateral is allowed if the other hip is evaluable with DXA)
- •Participant has a vitamin D deficiency
- •Participant has hypocalcaemia or hypercalcemia at the Screening Period
- •Participant has a history and/or presence of bone metastases, renal osteodystrophy, osteomyelitis, any metabolic, endocrine or traumatic bone disease
- •Participant has a current uncontrolled status of hypothyroidism or hyperthyroidism
- •Participant has a history (within 5 years prior to Screening) and/or current hypoparathyroidism or hyperparathyroidism
- •Participant has malignancy within 5 years before Screening
- •Participant has a history and/or presence of significant cardiac disease
- •Participant has a known intolerance or malabsorption of calcium or vitamin D supplements
- •Participant shows contraindications to denosumab therapy (e.g., hypocalcaemia), or calcium or vitamin D supplementation before starting test drug administration
- •Participant has a latex allergy
- •Participant has a history and/or presence of osteonecrosis of the jaw (ONJ) or risk factors for ONJ such as invasive dental procedures
- •Participant has history and/or presence of osteonecrosis of the external auditory canal
- •Participant requiring ongoing use of any osteoporosis treatment
- •Participant has previously received denosumab or biosimilar denosumab
- •Participant has weight or girth measurements which may preclude accurate DXA measurements
- •Participant has an active infection, including, but not limited to severe acute respiratory syndrome coronavirus-2, hepatis B, hepatitis C and human immunodeficiency virus infections during the Screening Period
研究组 & 干预措施
RGB-14-P (Main period)
Randomized participants will receive subcutaneous (SC) injection of RGB-14-P, on Day 1 of Treatment periods 1 and 2.
干预措施: RGB-14-P (Drug)
Prolia® (Main period)
Randomized participants will receive SC injection of Prolia®, on Day 1 of Treatment periods 1 and 2.
干预措施: Prolia® (Drug)
RGB-14-P (Transition period)
Re-randomized participants will receive SC injection of RGB-14-P, on Day 1 of Treatment period 3.
干预措施: RGB-14-P (Drug)
Prolia® (Transition period)
Re-randomized participants will receive SC injection of Prolia®, on Day 1 of Treatment period 3.
干预措施: Prolia® (Drug)
RGB-14-P (Continued till transition period)
Randomized participants will continue to receive SC injection of RGB-14-P from the main period till Day 1 of Treatment period 3.
干预措施: RGB-14-P (Drug)
结局指标
主要结局
Percentage Change From Baseline (%CfB) in Lumbar Spine Bone Mineral Density (BMD)
时间窗: Week 52
Percentage change from baseline in lumbar bone BMD was assessed. BMD at the lumbar spine was measured by dual-energy x-ray absorptiometry (DXA). This outcome measure was assessed for main period.
Area Under the Effective Curve (AUEC) After the First Dose Until Day 183 of %CfB in Serum Type I Collagen C-telopeptide (sCTX)
时间窗: Week 26
The AUEC of %CfB in sCTX of RGB-14-P was assessed as part of pharmacodynamics parameter with US-licensed Prolia® in female participants was demonstrated with postmenopausal osteoporosis. This outcome measure was assessed for main period only.
次要结局
- %CfB in Total Hip BMD(Weeks 26, 52 and 78)
- %CfB in Lumbar Spine BMD(Weeks 26 and 78)
- %CfB in Femoral Neck BMD(Weeks 26, 52 and 78)
- Number of Participants With Vertebral Fragility Fracture(Weeks 52 and 78)
- Number of Participants With Non-vertebral Fragility Fracture(Weeks 52 and 78)
- %CfB in Serum Procollagen Type 1 N Terminal Propeptide (P1NP)(Weeks 4, 26, 52 and 78)
- %CfB in Serum Type I Collagen C-telopeptide (sCTX)(Weeks 4, 26, 52 and 78)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Main Period: From screening (Weeks -5 to 0) to Week 52; Transition Period: From Week 52 to Week 78)
- Number of Participants With Anti-drug Antibodies (ADAs)(Weeks 0, 2, 4, 26, 28, 30, 52, 54, 56 and 78)
- Number of Participants With Neutralizing Antibodies(Weeks 0, 2, 4, 26, 28, 30, 52, 54, 56 and 78)
- Titre of ADAs(Weeks 0, 2, 4, 26, 28, 30, 52, 54, 56 and 78)