A Randomised, Double-blind, Parallel, Multinational Study to Compare the Efficacy, Pharmacokinetics, Pharmacodynamics, Safety and Immunogenicity of MB09 (Proposed Denosumab Biosimilar) vs. Prolia® (EU-sourced) in Postmenopausal Osteoporosis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 558
- 试验地点
- 64
- 主要终点
- Efficacy: Percentage Change From Baseline (%CfB) in Lumbar Spine Bone Mineral Density (LS-BMD) at 52 Weeks - Modified Full Analysis Set (mFAS)
研究概览
简要总结
This was a randomized, double-blind, parallel, multicenter, multinational study to compare the efficacy, pharmacokinetics, pharmacodynamics, safety and immunogenicity of MB09 versus Prolia® in postmenopausal women with osteoporosis
详细描述
The study was planning to randomise approximately 528 postmenopausal women with osteoporosis aged ≥55 and ≤80 years old with a Bone Mineral Density (BMD) consistent with T-score of ≤ -2.5 and ≥ -4 at the lumbar spine or total hip as measured by DXA during the Screening Period. Screening evaluations were to be completed within 28 days prior to randomisation.
On Day 1, 528 eligible postmenopausal women with osteoporosis were to be randomised in a 2:1:1 ratio to receive MB09-MB09 (Arm 1), Prolia-MB09 (Arm 2), or Prolia-Prolia (Arm 3) using an Interactive Response Sys-tem (IRT).
During the Main Treatment Period, subjects received one subcutaneous injection (60 mg/mL) of study drug on Day 1 and at Month 6. At Month 12, after all efficacy and safety assessments have been performed, the subject were to be enter the Transition/Safety Follow Up Period and were to receive the third dose of study drug. Subjects assigned to the MB09 MB09 arm (Arm 1) received MB09 on Day 1, at Month 6 and at Month 12. Subjects assigned to the Prolia MB09 arm (Arm 2) received EU-Prolia on Day 1 and at Month 6, and MB09 at Month 12. Subjects assigned to the Prolia-Prolia arm (Arm 3) received EU-Prolia on Day 1, at Month 6, and at Month 12. All subjects were to be followed up to Transition Period Month 6.
All subjects received daily supplementation of calcium and vitamin D.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 55 Years 至 80 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Postmenopausal women, diagnosed with osteoporosis.
- •Aged ≥ 55 and ≤ 80 years at screening.
- •Body weight ≥ 50 kg and ≤ 99.9 kg, and a body mass index of ≤30 kg/m2 at screening.
- •Absolute bone mineral density consistent with T-score ≤ -2.5 and ≥ -4.0 at the lumbar spine or total hip as measured by Dual-energy X-ray Absorptiometry (DXA).
- •At least two intact, nonfractured vertebrae in the L1-L4 region and at least one hip joint evaluable by DXA.
- •Adequate organ function.
排除标准
- •Previous exposure to denosumab (Prolia®, Xgeva®, or denosumab biosimilar) or other monoclonal antibody.
- •History and/or presence of one severe or more than two moderate vertebral fractures or hip fracture.
- •Recent long bone fracture (within 6 months).
- •History and/or presence of bone metastases, bone disease or other metabolic disease.
- •Intravenous bisphosphonate administered within 5 years of screening.
- •Oral bisphosphonates ≥12 months cumulative use prior to screening. If used <12 months cumulatively and the last dose was ≥12 months before screening, the subject could be enrolled.
- •Ongoing use of any osteoporosis treatment or use of prohibited treatment.
- •Other bone active drugs.
- •History and/or current hypoparathyroidism or hyperparathyroidism, hypocalcemia or hypercalcemia.
- •Other Inclusion/exclusion criteria may apply.
研究组 & 干预措施
MB09-MB09
Subjects randomised into MB09-MB09 group were administered MB09 (60 mg in 1 mL) SC injection every 6 months.
干预措施: MB09 (denosumab biosimilar) (Drug)
MB09-MB09
Subjects randomised into MB09-MB09 group were administered MB09 (60 mg in 1 mL) SC injection every 6 months.
干预措施: Elemental Calcium (Dietary Supplement)
MB09-MB09
Subjects randomised into MB09-MB09 group were administered MB09 (60 mg in 1 mL) SC injection every 6 months.
干预措施: Vitamin D (Dietary Supplement)
Prolia-MB09
Subjects randomised into Prolia- MB09 group were administered Prolia® (60 mg in 1 mL) SC injection every 6 months.
干预措施: MB09 (denosumab biosimilar) (Drug)
Prolia-MB09
Subjects randomised into Prolia- MB09 group were administered Prolia® (60 mg in 1 mL) SC injection every 6 months.
干预措施: EU-Prolia (Drug)
Prolia-MB09
Subjects randomised into Prolia- MB09 group were administered Prolia® (60 mg in 1 mL) SC injection every 6 months.
干预措施: Elemental Calcium (Dietary Supplement)
Prolia-MB09
Subjects randomised into Prolia- MB09 group were administered Prolia® (60 mg in 1 mL) SC injection every 6 months.
干预措施: Vitamin D (Dietary Supplement)
Prolia-Prolia
Subjects randomised into Prolia-Prolia group were administered Prolia® (60 mg in 1 mL) SC injection every 6 months.
干预措施: EU-Prolia (Drug)
Prolia-Prolia
Subjects randomised into Prolia-Prolia group were administered Prolia® (60 mg in 1 mL) SC injection every 6 months.
干预措施: Elemental Calcium (Dietary Supplement)
Prolia-Prolia
Subjects randomised into Prolia-Prolia group were administered Prolia® (60 mg in 1 mL) SC injection every 6 months.
干预措施: Vitamin D (Dietary Supplement)
结局指标
主要结局
Efficacy: Percentage Change From Baseline (%CfB) in Lumbar Spine Bone Mineral Density (LS-BMD) at 52 Weeks - Modified Full Analysis Set (mFAS)
时间窗: Baseline (Screening), up to Week 52
To demonstrate equivalent efficacy of MB09 to EU Prolia in postmenopausal women with osteoporosis in terms of lumbar spine BMD at Week 52 (Month 12). The main analysis method was on the mFAS using a mixed model for repeated measures (MMRM) fitted to the composite %CfB lumbar spine BMD at Month 6 and Month 12, without any imputation of missing data. Bone mineral density was assessed by dual-energy X-ray absorptiometry (DXA) and assessments of the lumbar spine (L1 to L4) were performed at a central imaging vendor.
次要结局
- Efficacy: Percent Change From Baseline in Lumbar Spine Bone Mineral Density (LS-BMD) at Week 52 - Full Analysis Set (FAS)(Baseline (screening), up to Week 52)
- Efficacy: Percentage Change From Baseline (%CfB) in Lumbar Spine at Month 6 and Total Hip and Femur Neck BMD at Month 6 and Month12 - MMRM on mFAS(Baseline (screening), Month 6 and Month 12.)
- Efficacy: Percentage Change From Baseline (%CfB) in Lumbar Spine BMD at Month 6 and Total Hip and Femur Neck BMD at Month 6 and 12 - ANCOVA on FAS(Baseline (screening), Month 6, Month 12.)
- Pharmacodynamics: Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (sCTX) Area Under the Effect Curve From Zero to 6 Months (AUEC0-6 Months) After First Dose - Modified Full Analysis Set (mFAS)(Baseline (pre-dose Day 1), up to Month 6.)
- Pharmacodynamics: %CfB Area Under the Percent Inhibition Curve From Time Zero to 6 Months (AUIC0-6 Months) in sCTX - on mFAS(Baseline (pre-dose Day 1), up to Month 6.)
- Pharmacokinetics: Maximum Observed Serum Concentration (Cmax) of Denosumab After First Dose Study Treatment (Pharmacokinetic Parameter Analysis Set)(Baseline (pre-dose Day 1), up to Month 6)
- Pharmacokinetics: To Assess the PK Profile of MB09 Compared With EU Prolia (AUC0-6 Months) Following the First Dose(Baseline (pre-dose Day 1), up to Month 6.)
- Safety: Overall Summary of Adverse Events - Main Treatment Period - Safety Analysis Set (SAF) and Safety Analysis Set for Transition Period (SAF-TP)(From first administration of study treatment on Day 1 until Month 18)
- Safety: New Clinical Bone Fractures - TEAEs (Throughout the Study - From Day 1 Untill Month 18)(All participants in the Main Treatment Period and Transition Period (From Day 1 untill Month 18))
- Overall Incidence of Antidrug Antibodies (ADA) - Safety Analysis Set (SAF) and Safety Analysis Set for Transition Period (SAF-TP)(From baseline (pre-dose) up to and including Month 18.)