This is a randomized, double-blind, international multicentre, parallel-controlled phase III clinical study. The study plans to enroll 478 postmenopausal women with osteoporosis at high risk of fracture, whom will be randomized at 1:1 to either the experiment group (HLX14) or the control group (Prolia®) based on stratification factors (BMI (\< 25, 25-30, \> 30) and geographic region (Asian or non-Asian)). The study includes screening period (28 days), treatment period (total 546 days, contain treatment period 1: D1-D364, treatment period 2: D365-D546), and an end-of-study visit (D547).
* Screening period: From Day -28 to -1, all female with postmenopausal osteoporosis subjects at high risk of fracture sign the informed consent form (ICF) and undergo relevant tests. Those who meet the inclusion criteria and do not meet the exclusion criteria will be randomly assigned into either experiment group (HLX14) or control group (Prolia®) at 1:1 and then enter the treatment period. Vitamin D and calcium supplementation is allowed during the screening period. * Treatment period: Subjects will receive a total of 3 doses of subcutaneous injection of HLX14 or Prolia® (once every 6 months (Q6M)). Treatment period 1: D1-D364, subjects will receive subcutaneous injection of HLX14 or Prolia® 60mg on D1 and D183. Treatment period 2: D365-D546, on D365, subjects in the Prolia® arm will be re-randomized 1:1 to either continue with a third dose of Prolia® or transition to HLX14 and receive a single dose of HLX14. Subjects in the HLX14 arm will be continue with a third dose of HLX14. * During the treatment period, subjects should taking at least 1000 mg of calcium daily and at least 400 IU of vitamin D daily until the end of study. (Dose will be adjusted by the investigator based on serum calcium) * End-of-study visit: The end-of-study visit will be conducted on D547 of the study or premature withdrawal. Only serious adverse events related to the investigational product will be recorded thereafter.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
514
Subjects will receive a total of 3 doses of subcutaneous injection of HLX14 (once every 6 months (Q6M)). Treatment period 1: D1-D364, subjects will receive subcutaneous injection of HLX14 60mg on D1 and D183. Treatment period 2: D365-D546, on D365, subjects will be continue with a third dose of HLX14.
Subjects will receive a total of 3 doses of subcutaneous injection of HLX14 or Prolia® (once every 6 months (Q6M)). Treatment period 1: D1-D364, subjects will receive subcutaneous injection of Prolia® 60mg on D1 and D183. Treatment period 2: D365-D546, on D365, subjects in the Prolia® arm will be re-randomized 1:1 to either continue with a third dose of Prolia® or transition to HLX14 and receive a single dose of HLX14.
The First Hospital of Hebei Medical University
Shijiazhuang, Hebei, China
The Fourth Affiliated Hospital of Harbin Medical University
Harbin, Heilongjiang, China
Inner Mongolia Baogang hospital
Baotou, Inner Mongolia, China
Huai'an First People's Hospital
Huai'an, Jiangsu, China
The Second Affiliated Hospital of Nanjing Medical University
Nanjing, Jiangsu, China
Primary efficacy endpoint
Percent change from baseline in BMD at the lumbar spine to Week 52 (D365) (assessed by the central imaging). Note: The percent change in BMD is calculated as: (Test value - Baseline value) / (Baseline Value) × 100%
Time frame: 52 Weeks
Primary pharmacodynamic endpoint
Area under the effect-time curve for percent change from baseline of serum type I collagen C-telopeptide (s-CTX) from 0 to Week 26 (D183) (AUEC0-26W)
Time frame: 26 Weeks
Secondary efficacy endpoint
1. Percent change from baseline in BMD at the lumbar spine to Week 26 (D183), Week 52 (D365),Week78 (D547) (assessed by investigator). 2. Fracture rate from baseline to Week 52 (D365), Week 78 (D547). 3. Percent change in BMD at lumbar spine from baseline to Week 26 (D183), Week 78 (D547) (assessed by the central imaging). 4. Percent change in BMD at total hip from baseline to Week 26 (D183), Week 52 (D365) and Week 78 (D547) (assessed by the central imaging and investigator). 5. Percent change in BMD at the femoral neck from baseline to Week 26 (D183), Week 52 (D365) and Week 78 (D547) (assessed by the central imaging and investigator). Note: Fracture rate=(number of patients with new fractures/total number of patients)\*100% The percent change in BMD is calculated as (test value - baseline value) ÷ (baseline value) × 100%
Time frame: 78 Weeks
Secondary pharmacodynamic endpoint
1. Relative percent change in serum type I collagen C-telopeptide (s-CTX) from baseline to D15, D29, D57, D92, D106, D134, D162, D183 (within 7 days prior to the second dose), D274, D365 (within 7 days prior to the third dose), and D547 (at the end-of-study visit). 2. Relative percent changes in serum procollagen type I N propeptide (s-P1NP) from baseline to D15, D29, D57, D92, D106, D134, D162, D183 (within 7 days prior to the second dose), D274, D365 (within 7 days prior to the third dose) and D547 (at the end-of-study visit). The relative percent change is calculated as: (Test value at timepoints evaluated - Baseline value) / (Baseline value) × 100%
Time frame: 78 Weeks
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Affiliated Hospital of Xuzhou Medical University
Xuzhou, Jiangsu, China
Ruian People's Hospital
Rui'an, Jiangxi, China
People's Hospital of Ningxia Hui Autonomous Region
Yinchuan, Ningxia, China
Zhejiang Provincial People's Hospital
Hangzhou, Zhejiang, China
Beijing BOAI Hospital
Beijing, China
...and 28 more locations