DRUG
Placebo to Romosozumab
Administered by subcutaneous injection QM or Q3M.
Romosozumab (AMG 785) in Postmenopausal Women With Low Bone Mineral Density
Status
Completed
Phase
Phase 2
Enrollment
419
Locations
0
Results
Posted
Publications
8
Study summary
What the protocol is testing.
The primary objective was to determine the effect of treatment with romosozumab versus placebo at month 12 on the percent change from baseline in bone mineral density (BMD) at the lumbar spine in postmenopausal women with low bone density.
Full detailed description
This study included a 24-month treatment phase followed by rerandomization to a 12-month extension phase with denosumab or placebo, followed by a 12-month retreatment phase with romosozumab, followed by a 24-month follow-on phase with zoledronic acid or no intervention. * 24-month Romosozumab Treatment Phase (months 1 to 24): Participants were randomized in a 1:1:1:1:1:1:1:1 ratio to receive 1 of 5 double-blind dosing regimens of romosozumab or placebo or open-label alendronate (ALN) or open-label teriparatide (TPTD) for the first 12 months of the study. At month 12, participants in the romosozumab and placebo groups continued their assigned treatment for an additional 12 months, participants in the TPTD group ended study participation, and participants in the ALN group transitioned to receive romosozumab 140 mg subcutaneously (SC) every month (QM) for an additional 12 months (months 12 to 24). * 12-month Denosumab Extension Phase (months 24 to 36): At the end of the 24-month romosozumab treatment phase, eligible participants were randomized 1:1 within their original treatment group to receive either denosumab or placebo every 6 months (Q6M) for 12 months. * 12-month Romosozumab Retreatment Phase (months 36 to 48): From months 36 to 48, participants initially randomized to romosozumab or placebo received romosozumab 210 mg SC QM. Participants who initially received ALN ended their participation at month 36 and were not retreated with romosozumab. * 24-month Follow-on Phase (months 48 to 72): At month 48, participants received 1 dose of zoledronic acid 5 mg intravenously or no intervention for an additional 24 months.
Interventions
Treatment arms and agents.
DRUG
Alendronate
Administered orally once a week
DRUG
Teriparatide
Teriparatide 20 μg administered by subcutaneous injection once a day
DRUG
Romosozumab
Administered by subcutaneous injection
DRUG
Denosumab
Denosumab 60 mg administered by subcutaneous injection Q6M
DRUG
Placebo to Denosumab
Administered by subcutaneous injection Q6M
DRUG
Zoledronic acid
Zoledronic acid 5 mg administered intravenously
Timeline
From registration to results.
First posted
May 11, 2009
Study start
Jun 3, 2009
Primary completion
Feb 21, 2011
Study completion
Feb 18, 2016
Results posted
Dec 14, 2018
Registry updated
Sep 22, 2022
Outcomes
What the study measures.
Primary outcomes
Percent Change From Baseline at Month 12 in BMD at the Lumbar Spine
Time frame · Baseline to 12 months
Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader.
Secondary outcomes
Percent Change From Baseline at Month 6 in BMD at the Lumbar Spine
Time frame · Baseline to 6 months
Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader. Percent change from baseline to month 6 was analyzed using a linear mixed effects model with the percent change from baseline to month 6 in DXA BMD as dependent variable, and baseline BMD value, machine type, geographic region, interaction of baseline BMD and machine type, visit, treatment (categorical) and interaction of treatment and visit as the independent variables.
Percent Change From Baseline at Month 6 in BMD of the Total Hip
Time frame · Baseline to 6 months
Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader. Percent change from baseline to month 6 was analyzed using a linear mixed effects model with the percent change from baseline to month 6 in DXA BMD as dependent variable, and baseline BMD value, machine type, geographic region, interaction of baseline BMD and machine type, visit, treatment (categorical) and interaction of treatment and visit as the independent variables.
Percent Change From Baseline at Month 6 in BMD of the Femoral Neck
Time frame · Baseline to 6 months
Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader. Percent change from baseline to month 6 was analyzed using a linear mixed effects model with the percent change from baseline to month 6 in DXA BMD as dependent variable, and baseline BMD value, machine type, geographic region, interaction of baseline BMD and machine type, visit, treatment (categorical) and interaction of treatment and visit as the independent variables.
Percent Change From Baseline at Month 12 in BMD of the Total Hip
Time frame · Baseline to 12 months
Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader. Percent change from baseline to 12 months in BMD was analyzed using a linear mixed effects model with the percent change from baseline to month 12 in DXA BMD as dependent variable, and baseline BMD value, machine type, geographic region, interaction of baseline BMD and machine type, visit, treatment (categorical) and interaction of treatment and visit as the independent variables.
Percent Change From Baseline at Month 12 in BMD of the Femoral Neck
Time frame · Baseline to 12 months
Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader. Percent change from baseline to 12 months in BMD was analyzed using a linear mixed effects model with the percent change from baseline to month 12 in DXA BMD as dependent variable, and baseline BMD value, machine type, geographic region, interaction of baseline BMD and machine type, visit, treatment (categorical) and interaction of treatment and visit as the independent variables.
Percent Change From Baseline at Month 12 in BMD of the Distal Radius
Time frame · Baseline to 12 months
Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader. Percent change from baseline in distal radius BMD was analyzed using an analysis of covariance (ANCOVA) model with the percent change from baseline to Month 12 in DXA BMD as dependent variable, baseline BMD value, machine type, interaction of baseline BMD and machine type, treatment (categorical) and geographic region as the independent class variables.
Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP)
Time frame · Baseline and months 1, 3, 6, 9, and 12
Percent change from baseline in the bone turnover marker (BTM) P1NP was analyzed using a linear mixed effects model with the natural logarithm of the ratio of BTM (follow-up versus baseline) as the dependent variables, and visit, treatment (categorical), interaction of treatment and visit and the natural logarithm of the baseline BTM as the independent variables; outcomes were then transformed back to percent change from baseline.
Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX)
Time frame · Baseline and months 1, 3, 6, 9, and 12
Percent change from baseline in the bone turnover marker (BTM) CTX was analyzed using a linear mixed effects model with the natural logarithm of the ratio of BTM (follow-up versus baseline) as the dependent variables, and visit, treatment (categorical), interaction of treatment and visit and the natural logarithm of the baseline BTM as the independent variables; outcomes were then transformed back to percent change from baseline.
Percent Change From Baseline in Osteocalcin
Time frame · Baseline and months 1, 3, 6, 9, and 12
Percent change from baseline in the bone turnover marker (BTM) osteocalcin was analyzed using a linear mixed effects model with the natural logarithm of the ratio of BTM (follow-up versus baseline) as the dependent variables, and visit, treatment (categorical), interaction of treatment and visit and the natural logarithm of the baseline BTM as the independent variables; outcomes were then transformed back to percent change from baseline.
Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP)
Time frame · Baseline and months 1, 3, 6, 9, and 12
Percent change from baseline in the bone turnover marker (BTM) BSAP was analyzed using a linear mixed effects model with the natural logarithm of the ratio of BTM (follow-up versus baseline) as the dependent variables, and visit, treatment (categorical), interaction of treatment and visit and the natural logarithm of the baseline BTM as the independent variables; outcomes were then transformed back to percent change from baseline.
Eligibility
Who can take part.
- Minimum age
- 55 Years
- Maximum age
- 85 Years
- Sex
- FEMALE
- Healthy volunteers
- No
Inclusion Criteria: * Ambulatory, postmenopausal women, aged ≥ 55 to ≤ 85 * Low BMD measured by dual energy X-ray absorptiometry (DXA) and assessed by the central imaging vendor (equivalent to T-scores between -2.0 and -3.5) Exclusion Criteria: * History of vertebral fracture, or fragility fracture of the wrist, humerus, hip or pelvis after age 50 * Untreated hyper- or hypothyroidism * Current hyper- or hypoparathyroidism, hypo- or hypercalcemia * Elevated transaminases * Significantly impaired renal function * Positive for: human immunodeficiency virus (HIV), hepatitis-C or hepatitis-B surface antigen * Malignancy * History of solid organ or bone marrow transplants * Use of agents affecting bone metabolism * Contraindicated or intolerant of alendronate therapy * Contraindicated or intolerant of teriparatide therapy Inclusion Criteria for the 12 month extension phase (Month 24 to 36): \- Normocalcemia at or after the Month 21 visit but before the Month 24 study visit Exclusion Criteria for the 12 month extension phase (Month 24 to 36) * Incidence of a clinical vertebral fracture or fragility fracture of the wrist, humerus, hip or pelvis during the initial 24 month treatment phase of the study * A BMD loss of ≥ 7.0% from baseline at any time up to the Month 18 visit of the initial 24-month treatment phase * Malignancy * History of osteonecrosis of the jaw * Use of proscribed medication during the initial 24 month treatment phase * Contraindicated or intolerant of denosumab therapy Inclusion Criteria for the 12 month re-treatment phase (Month 36 to 48) * Albumin adjusted serum calcium of the most recent blood draw at or after the Month 30 visit but before the Month 36 study visit. Calcium repletion is permitted and central laboratory analysis of albumin adjusted serum calcium may be repeated before the Month 36 study visit * Participation in Group A or B during initial 24 month treatment phase * Subject has reached M36 of the study * Appropriate written informed consent must be obtained Exclusion Criteria for the 12 month re-treatment phase (Month 36 to 48) * New malignancy * Use of proscribed medication during the 12 month extension phase Inclusion Criteria for the 24 month follow-on phase (Month 48 to 72) General inclusion criteria for participation * Subject has reached month 48 of the study * Appropriate written informed consent must be obtained Inclusion criteria for assignment to the no intervention group * During the 24 month AMG 785 treatment phase, subject was assigned to any AMG 785 treatment group * During the 12 month denosumab extension phase, subject was assigned to the denosumab treatment group Exclusion for the 24 month follow-on phase (Month 48 to 72) * New malignancy * Use of proscribed meds during the 12 month re-treatment phase * Partial informed consent withdrawal and discontinuation of investigational product at any time up to month 48 visit * Incidence of a clinical vertebral fracture or fragility fracture of the wrist, humerus, hip or pelvis during the initial 24 month treatment phase of the study * BMD T-score of ≤ -2.5 at the lumbar spine, total hip, or femoral neck based on local read of the DXA scans at month 48 * Intolerance to zoledronic acid
Study locations
0 registered sites.
No country data reported. Showing up to 24 locations stored in the fast local snapshot.
No study locations reported.
Publications
Results and literature.
PMID 27487526 ↗Genant HK, Engelke K, Bolognese MA, Mautalen C, Brown JP, Recknor C, Goemaere S, Fuerst T, Yang YC, Grauer A, Libanati C. Effects of Romosozumab Compared With Teriparatide on Bone Density and Mass at the Spine and Hip in Postmenopausal Women With Low Bone Mass. J Bone Miner Res. 2017 Jan;32(1):181-187. doi: 10.1002/jbmr.2932. Epub 2016 Sep 20.PMID 28543940 ↗Keaveny TM, Crittenden DB, Bolognese MA, Genant HK, Engelke K, Oliveri B, Brown JP, Langdahl BL, Yan C, Grauer A, Libanati C. Greater Gains in Spine and Hip Strength for Romosozumab Compared With Teriparatide in Postmenopausal Women With Low Bone Mass. J Bone Miner Res. 2017 Sep;32(9):1956-1962. doi: 10.1002/jbmr.3176. Epub 2017 Jun 26.PMID 31628490 ↗Kendler DL, Bone HG, Massari F, Gielen E, Palacios S, Maddox J, Yan C, Yue S, Dinavahi RV, Libanati C, Grauer A. Bone mineral density gains with a second 12-month course of romosozumab therapy following placebo or denosumab. Osteoporos Int. 2019 Dec;30(12):2437-2448. doi: 10.1007/s00198-019-05146-9. Epub 2019 Oct 18.PMID 29694685 ↗McClung MR, Brown JP, Diez-Perez A, Resch H, Caminis J, Meisner P, Bolognese MA, Goemaere S, Bone HG, Zanchetta JR, Maddox J, Bray S, Grauer A. Effects of 24 Months of Treatment With Romosozumab Followed by 12 Months of Denosumab or Placebo in Postmenopausal Women With Low Bone Mineral Density: A Randomized, Double-Blind, Phase 2, Parallel Group Study. J Bone Miner Res. 2018 Aug;33(8):1397-1406. doi: 10.1002/jbmr.3452. Epub 2018 May 22.PMID 32623487 ↗McClung MR, Bolognese MA, Brown JP, Reginster JY, Langdahl BL, Maddox J, Shi Y, Rojeski M, Meisner PD, Grauer A. A single dose of zoledronate preserves bone mineral density for up to 2 years after a second course of romosozumab. Osteoporos Int. 2020 Nov;31(11):2231-2241. doi: 10.1007/s00198-020-05502-0. Epub 2020 Jul 4.PMID 34258507 ↗McClung MR, Bolognese MA, Brown JP, Reginster JY, Langdahl BL, Shi Y, Timoshanko J, Libanati C, Chines A, Oates MK. Skeletal responses to romosozumab after 12 months of denosumab. JBMR Plus. 2021 Jun 3;5(7):e10512. doi: 10.1002/jbm4.10512. eCollection 2021 Jul.PMID 34738660 ↗Poole KE, Treece GM, Pearson RA, Gee AH, Bolognese MA, Brown JP, Goemaere S, Grauer A, Hanley DA, Mautalen C, Recknor C, Yang YC, Rojeski M, Libanati C, Whitmarsh T. Romosozumab Enhances Vertebral Bone Structure in Women With Low Bone Density. J Bone Miner Res. 2022 Feb;37(2):256-264. doi: 10.1002/jbmr.4465. Epub 2021 Dec 16.PMID 24382002 ↗McClung MR, Grauer A, Boonen S, Bolognese MA, Brown JP, Diez-Perez A, Langdahl BL, Reginster JY, Zanchetta JR, Wasserman SM, Katz L, Maddox J, Yang YC, Libanati C, Bone HG. Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med. 2014 Jan 30;370(5):412-20. doi: 10.1056/NEJMoa1305224. Epub 2014 Jan 1.
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