Hideaki Ishibashi1, Daria B Crittenden2, Akimitsu Miyauchi3, Cesar Libanati4, Judy Maddox5, Michelle Fan6, Li Chen7, Andreas Grauer8. 1. INA Hospital, Saitama, Japan. Electronic address: hbashi@jcom.home.ne.jp. 2. Amgen Inc., Thousand Oaks, CA, USA. Electronic address: dcritten@amgen.com. 3. Miyauchi Medical Center, Osaka, Japan. 4. UCB Pharma, Brussels, Belgium. Electronic address: Cesar.Libanati@ucb.com. 5. Amgen Inc., Thousand Oaks, CA, USA. Electronic address: jmaddox@amgen.com. 6. Amgen Inc., Thousand Oaks, CA, USA. Electronic address: mfan@amgen.com. 7. Amgen Inc., Thousand Oaks, CA, USA. Electronic address: lic@amgen.com. 8. Amgen Inc., Thousand Oaks, CA, USA. Electronic address: agrauer@amgen.com.
Abstract
BACKGROUND:Romosozumab is a monoclonal antibody that inhibits sclerostin and rapidly increases bone mineral density (BMD) through a dual effect on bone by increasing bone formation and decreasing bone resorption, as shown in a global phase 2 study in postmenopausal women with low bone mass. Here, we report the key results of a phase 2, double-blind, placebo-controlled, dose-ranging study to assess the efficacy and safety of romosozumab in postmenopausal Japanese women with osteoporosis. METHODS:Participants were postmenopausal Japanese women with osteoporosisaged 55-85years with a lumbar spine, total hip, or femoral neck dual-energy X-ray absorptiometry T-score≤-2.5. Women were randomized to receive placebo or romosozumab (70, 140, or 210mg) subcutaneously once monthly (QM) for 12months. The primary efficacy endpoint was the percentage change from baseline in lumbar spine BMD at month 12. Secondary efficacy endpoints included the percentage change from baseline in lumbar spine BMD at month 6, total hip and femoral neck BMD at months 6 and 12, and serum bone turnover markers procollagen type 1N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX) at multiple visits. RESULTS: This study enrolled 252 women who had a mean age of 67.7years and mean T-scores of -2.7, -1.9, and -2.3 at the lumbar spine, total hip, and femoral neck, respectively. All romosozumab doses significantly increased BMD at month 12 compared with placebo (p<0.01), with the largest mean gains from baseline observed with romosozumab 210mg QM (lumbar spine=16.9%, total hip=4.7%, and femoral neck=3.8%). All doses of romosozumab significantly increased the levels of bone-formation marker P1NP and reduced the levels of bone-resorption marker CTX by week 1 (p<0.001 vs placebo). In the 210mg QM group, P1NP levels peaked at month 1 and fell below placebo levels by month 12; CTX levels were lowest at week 1 and remained below placebo through month 12. The patient incidences of adverse events and serious adverse events were generally comparable between treatment groups. CONCLUSIONS: In postmenopausal Japanese women with osteoporosis, romosozumab treatment resulted in large and significant gains in BMD from baseline and compared with placebo. Romosozumab 210mg QM showed the largest gains in BMD and was generally well tolerated. The efficacy and safety of romosozumab 210mg QM in this phase 2 study of postmenopausal women with osteoporosis were similar to those in an international phase 2 study.
RCT Entities:
BACKGROUND:Romosozumab is a monoclonal antibody that inhibits sclerostin and rapidly increases bone mineral density (BMD) through a dual effect on bone by increasing bone formation and decreasing bone resorption, as shown in a global phase 2 study in postmenopausal women with low bone mass. Here, we report the key results of a phase 2, double-blind, placebo-controlled, dose-ranging study to assess the efficacy and safety of romosozumab in postmenopausal Japanese women with osteoporosis. METHODS:Participants were postmenopausal Japanese women with osteoporosis aged 55-85years with a lumbar spine, total hip, or femoral neck dual-energy X-ray absorptiometry T-score≤-2.5. Women were randomized to receive placebo or romosozumab (70, 140, or 210mg) subcutaneously once monthly (QM) for 12months. The primary efficacy endpoint was the percentage change from baseline in lumbar spine BMD at month 12. Secondary efficacy endpoints included the percentage change from baseline in lumbar spine BMD at month 6, total hip and femoral neck BMD at months 6 and 12, and serum bone turnover markers procollagen type 1N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX) at multiple visits. RESULTS: This study enrolled 252 women who had a mean age of 67.7years and mean T-scores of -2.7, -1.9, and -2.3 at the lumbar spine, total hip, and femoral neck, respectively. All romosozumab doses significantly increased BMD at month 12 compared with placebo (p<0.01), with the largest mean gains from baseline observed with romosozumab 210mg QM (lumbar spine=16.9%, total hip=4.7%, and femoral neck=3.8%). All doses of romosozumab significantly increased the levels of bone-formation marker P1NP and reduced the levels of bone-resorption marker CTX by week 1 (p<0.001 vs placebo). In the 210mg QM group, P1NP levels peaked at month 1 and fell below placebo levels by month 12; CTX levels were lowest at week 1 and remained below placebo through month 12. The patient incidences of adverse events and serious adverse events were generally comparable between treatment groups. CONCLUSIONS: In postmenopausal Japanese women with osteoporosis, romosozumab treatment resulted in large and significant gains in BMD from baseline and compared with placebo. Romosozumab 210mg QM showed the largest gains in BMD and was generally well tolerated. The efficacy and safety of romosozumab 210mg QM in this phase 2 study of postmenopausal women with osteoporosis were similar to those in an international phase 2 study.
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