Low Bone Mineral DensityPhase 2NCT00896532

Romosozumab (AMG 785) in Postmenopausal Women With Low Bone Mineral Density

A Phase 2 study testing Alendronate, Teriparatide and Romosozumab in people with Low Bone Mineral Density and Postmenopausal Osteoporosis, run by Amgen.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 55 to 85 years, women only
Conditions the study is for: Low Bone Mineral Density, Postmenopausal Osteoporosis
What is being tested?: Alendronate, Teriparatide and Romosozumab
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 419 participants
Where: No sites listed yet
Study dates: 3 Jun 2009to 18 Feb 2016
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 55 to 85 years
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

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)

Who cannot join

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

Show all 39Show fewer

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

About this study

Official title: A Randomised, Placebo-controlled, Multi-dose Phase 2 Study to Determine the Efficacy, Safety and Tolerability of AMG 785 in the Treatment of Postmenopausal Women With Low Bone Mineral Density

Read the 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.

Conditions: Low Bone Mineral Density, Postmenopausal Osteoporosis
Being tested: Placebo to Romosozumab, Alendronate, Teriparatide, Romosozumab, Denosumab
Medical subject headings: Bone Diseases, Metabolic, Osteoporosis, Postmenopausal

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Placebo to RomosozumabDrug
Administered by subcutaneous injection QM or Q3M.
AlendronateDrug
Also called Fosamax
Administered orally once a week
TeriparatideDrug
Also called Forsteo
Teriparatide 20 μg administered by subcutaneous injection once a day
RomosozumabDrug
Also called AMG 785, EVENITY™
Administered by subcutaneous injection
DenosumabDrug
Also called Prolia®
Denosumab 60 mg administered by subcutaneous injection Q6M
Placebo to DenosumabDrug
Administered by subcutaneous injection Q6M
Zoledronic acidDrug
Also called Aclasta
Zoledronic acid 5 mg administered intravenously

Study groups in NCT00896532
Study group	Role	What they receive
Placebo	Placebo comparator	Participants received placebo matching to romosozumab once a month (QM) or once every 3 months (Q3M) administered subcutaneously (SC) for up to 24 months. Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. From months 36 to 48 participants received romosozumab 210 mg SC QM. At month 48 eligible participants received a single dose of open-label zoledronic acid 5 mg intravenously, or no intervention. Receives: Drug: Placebo to Romosozumab; Drug: Denosumab; Drug: Placebo to Denosumab; Drug: Zoledronic acid
Alendronate	Active comparator	Participants received open-label alendronate (ALN) 70 mg orally (PO) every week (QW) for 12 months. At month 12 participants transitioned to receive romosozumab 140 mg subcutaneously every month for an additional 12 months (months 12 to 24). Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. At month 36 participants ended study participation. Receives: Drug: Alendronate; Drug: Romosozumab; Drug: Denosumab; Drug: Placebo to Denosumab
Teriparatide	Active comparator	Participants received open-label teriparatide 20 μg subcutaneously every day (QD) for 12 months. At month 12 participants ended study participation. Receives: Drug: Teriparatide
Romosozumab 70 mg QM	Experimental	Participants received double-blind romosozumab 70 mg subcutaneously every month for 24 months. Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. From months 36 to 48 participants received romosozumab 210 mg SC QM. At month 48 eligible participants received a single dose of open-label zoledronic acid 5 mg intravenously, or no intervention. Receives: Drug: Romosozumab; Drug: Denosumab; Drug: Placebo to Denosumab; Drug: Zoledronic acid
Romosozumab 140 mg Q3M	Experimental	Participants received double-blind romosozumab 140 mg subcutaneously once every 3 months for 24 months. Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. From months 36 to 48 participants received romosozumab 210 mg SC QM. At month 48 eligible participants received a single dose of open-label zoledronic acid 5 mg intravenously, or no intervention. Receives: Drug: Romosozumab; Drug: Denosumab; Drug: Placebo to Denosumab; Drug: Zoledronic acid
Romosozumab 140 mg QM	Experimental	Participants received double-blind romosozumab 140 mg QM subcutaneously for 24 months. Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. From months 36 to 48 participants received romosozumab 210 mg SC QM. At month 48 eligible participants received a single dose of open-label zoledronic acid 5 mg intravenously, or no intervention. Receives: Drug: Romosozumab; Drug: Denosumab; Drug: Placebo to Denosumab; Drug: Zoledronic acid
Romosozumab 210 mg Q3M	Experimental	Participants received double-blind romosozumab 210 mg Q3M subcutaneously for 24 months. Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. From months 36 to 48 participants received romosozumab 210 mg SC QM. At month 48 eligible participants received a single dose of open-label zoledronic acid 5 mg intravenously, or no intervention. Receives: Drug: Romosozumab; Drug: Denosumab; Drug: Placebo to Denosumab; Drug: Zoledronic acid
Romosozumab 210 mg QM	Experimental	Participants received double-blind romosozumab 210 mg QM subcutaneously for 24 months. Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. From months 36 to 48 participants received romosozumab 210 mg SC QM. At month 48 eligible participants received a single dose of open-label zoledronic acid 5 mg intravenously, or no intervention. Receives: Drug: Romosozumab; Drug: Denosumab; Drug: Placebo to Denosumab; Drug: Zoledronic acid

What is being measured

The primary outcome is the main question the study is designed to answer.

Percent Change From Baseline at Month 12 in BMD at the Lumbar Spine
Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader.
Measured: Baseline to 12 months

Secondary outcomes (10)

Percent Change From Baseline at Month 6 in BMD at the Lumbar Spine
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.
Measured: Baseline to 6 months
Percent Change From Baseline at Month 6 in BMD of the Total Hip
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.
Measured: Baseline to 6 months
Percent Change From Baseline at Month 6 in BMD of the Femoral Neck
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.
Measured: Baseline to 6 months
Percent Change From Baseline at Month 12 in BMD of the Total Hip
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.
Measured: Baseline to 12 months
Percent Change From Baseline at Month 12 in BMD of the Femoral Neck
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.
Measured: Baseline to 12 months
Percent Change From Baseline at Month 12 in BMD of the Distal Radius
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.
Measured: Baseline to 12 months
Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP)
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.
Measured: Baseline and months 1, 3, 6, 9, and 12
Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX)
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.
Measured: Baseline and months 1, 3, 6, 9, and 12
Percent Change From Baseline in Osteocalcin
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.
Measured: Baseline and months 1, 3, 6, 9, and 12
Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP)
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.
Measured: Baseline and months 1, 3, 6, 9, and 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

3 Jun 200918 Feb 2016

First posted11 May 2009 (estimated)
Study start3 Jun 2009
Primary completion21 Feb 2011
Study completion18 Feb 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (8)Papers the sponsor has linked to this study.
Other trials for Low Bone Mineral DensityStudies of the same condition, open and under way.
More trials run by AmgenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 419 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00896532
Sponsor's protocol ID: 20060326
Other IDs: 2008-005991-28, 2008
Status last verified: Sep 2022
First submitted: 7 May 2009
Last updated: 22 Sep 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 27487526
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.
PubMed 28543940
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.
PubMed 31628490
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.
PubMed 29694685
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.
PubMed 32623487
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.
PubMed 34258507
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.
PubMed 34738660
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.
PubMed 24382002

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 22 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomised, Placebo-controlled, Multi-dose Phase 2 Study to Determine the Efficacy, Safety and Tolerability of AMG 785 in the Treatment of Postmenopausal Women With Low Bone Mineral Density
ClinicalTrials.gov ID: NCT00896532
Acronym / sponsor ID: 20060326
Conditions: Low Bone Mineral Density, Postmenopausal Osteoporosis
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 419 participants (actual)
Lead sponsor: AmgenIndustry (pharma, biotech, devices)
Study start: 3 Jun 2009 (actual)
Primary completion: 21 Feb 2011 (actual)
Study completion: 18 Feb 2016 (actual)
First posted: 11 May 2009 (estimated)
Results: Posted 14 Dec 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 8

Arm	Type	Receives
Placebo	Placebo comparator	Drug: Placebo to Romosozumab, Drug: Denosumab, Drug: Placebo to Denosumab, Drug: Zoledronic acidParticipants received placebo matching to romosozumab once a month (QM) or once every 3 months (Q3M) administered subcutaneously (SC) for up to 24 months. Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. From months 36 to 48 participants received romosozumab 210 mg SC QM. At month 48 eligible participants received a single dose of open-label zoledronic acid 5 mg intravenously, or no intervention.
Alendronate	Active comparator	Drug: Alendronate, Drug: Romosozumab, Drug: Denosumab, Drug: Placebo to DenosumabParticipants received open-label alendronate (ALN) 70 mg orally (PO) every week (QW) for 12 months. At month 12 participants transitioned to receive romosozumab 140 mg subcutaneously every month for an additional 12 months (months 12 to 24). Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. At month 36 participants ended study participation.
Teriparatide	Active comparator	Drug: TeriparatideParticipants received open-label teriparatide 20 μg subcutaneously every day (QD) for 12 months. At month 12 participants ended study participation.
Romosozumab 70 mg QM	Experimental	Drug: Romosozumab, Drug: Denosumab, Drug: Placebo to Denosumab, Drug: Zoledronic acidParticipants received double-blind romosozumab 70 mg subcutaneously every month for 24 months. Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. From months 36 to 48 participants received romosozumab 210 mg SC QM. At month 48 eligible participants received a single dose of open-label zoledronic acid 5 mg intravenously, or no intervention.
Romosozumab 140 mg Q3M	Experimental	Drug: Romosozumab, Drug: Denosumab, Drug: Placebo to Denosumab, Drug: Zoledronic acidParticipants received double-blind romosozumab 140 mg subcutaneously once every 3 months for 24 months. Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. From months 36 to 48 participants received romosozumab 210 mg SC QM. At month 48 eligible participants received a single dose of open-label zoledronic acid 5 mg intravenously, or no intervention.
Romosozumab 140 mg QM	Experimental	Drug: Romosozumab, Drug: Denosumab, Drug: Placebo to Denosumab, Drug: Zoledronic acidParticipants received double-blind romosozumab 140 mg QM subcutaneously for 24 months. Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. From months 36 to 48 participants received romosozumab 210 mg SC QM. At month 48 eligible participants received a single dose of open-label zoledronic acid 5 mg intravenously, or no intervention.
Romosozumab 210 mg Q3M	Experimental	Drug: Romosozumab, Drug: Denosumab, Drug: Placebo to Denosumab, Drug: Zoledronic acidParticipants received double-blind romosozumab 210 mg Q3M subcutaneously for 24 months. Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. From months 36 to 48 participants received romosozumab 210 mg SC QM. At month 48 eligible participants received a single dose of open-label zoledronic acid 5 mg intravenously, or no intervention.
Romosozumab 210 mg QM	Experimental	Drug: Romosozumab, Drug: Denosumab, Drug: Placebo to Denosumab, Drug: Zoledronic acidParticipants received double-blind romosozumab 210 mg QM subcutaneously for 24 months. Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. From months 36 to 48 participants received romosozumab 210 mg SC QM. At month 48 eligible participants received a single dose of open-label zoledronic acid 5 mg intravenously, or no intervention.

Who may qualify

Ages: 55 to 85 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

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)

Key exclusion criteria (39 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Placebo to RomosozumabAdministered by subcutaneous injection QM or Q3M.	Drug	Placebo
AlendronateAlso: FosamaxAdministered orally once a week	Drug	Alendronate
TeriparatideAlso: ForsteoTeriparatide 20 μg administered by subcutaneous injection once a day	Drug	Teriparatide
RomosozumabAlso: AMG 785, EVENITY™Administered by subcutaneous injection	Drug	Alendronate, Romosozumab 140 mg Q3M, Romosozumab 140 mg QM, Romosozumab 210 mg Q3M, Romosozumab 210 mg QM, Romosozumab 70 mg QM
DenosumabAlso: Prolia®Denosumab 60 mg administered by subcutaneous injection Q6M	Drug	Alendronate, Placebo, Romosozumab 140 mg Q3M, Romosozumab 140 mg QM, Romosozumab 210 mg Q3M, Romosozumab 210 mg QM, Romosozumab 70 mg QM
Placebo to DenosumabAdministered by subcutaneous injection Q6M	Drug	Alendronate, Placebo, Romosozumab 140 mg Q3M, Romosozumab 140 mg QM, Romosozumab 210 mg Q3M, Romosozumab 210 mg QM, Romosozumab 70 mg QM
Zoledronic acidAlso: AclastaZoledronic acid 5 mg administered intravenously	Drug	Placebo, Romosozumab 140 mg Q3M, Romosozumab 140 mg QM, Romosozumab 210 mg Q3M, Romosozumab 210 mg QM, Romosozumab 70 mg QM

Primary outcome

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.

10 secondary outcomes

Percent Change From Baseline at Month 6 in BMD at the Lumbar Spine
Time frame: Baseline to 6 months
Percent Change From Baseline at Month 6 in BMD of the Total Hip
Time frame: Baseline to 6 months
Percent Change From Baseline at Month 6 in BMD of the Femoral Neck
Time frame: Baseline to 6 months
Percent Change From Baseline at Month 12 in BMD of the Total Hip
Time frame: Baseline to 12 months
Percent Change From Baseline at Month 12 in BMD of the Femoral Neck
Time frame: Baseline to 12 months
Percent Change From Baseline at Month 12 in BMD of the Distal Radius
Time frame: Baseline to 12 months
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 Type 1 Collagen C-telopeptide (CTX)
Time frame: Baseline and months 1, 3, 6, 9, and 12
Percent Change From Baseline in Osteocalcin
Time frame: Baseline and months 1, 3, 6, 9, and 12
Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP)
Time frame: Baseline and months 1, 3, 6, 9, and 12

Results and safety

Results posted to the registry on 14 Dec 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	52	46
Alendronate	51	45
Teriparatide	55	46
Romosozumab 70 mg QM	51	39
Romosozumab 140 mg Q3M	54	46
Romosozumab 140 mg QM	51	43
Romosozumab 210 mg Q3M	53	48
Romosozumab 210 mg QM	52	48
Month 24-36: Placebo/Placebo	0	0
Month 24-36: Placebo/Denosumab	0	0
Month 24-36: Alendronate/Romosozumab/Placebo	0	0
Month 24-36: Alendronate/Romosozumab/Denosumab	0	0
Month 24-36: Romosozumab/Placebo	0	0
Month 24-36: Romosozumab/Denosumab	0	0
Month 36-48: Placebo/Placebo/Romosozumab	0	0
Month 36-48: Placebo/Denosumab/Romosozumab	0	0
Month 36-48: Romosozumab/Placebo/Romosozumab	0	0
Month 36-48: Romosozumab/Denosumab/Romosozumab	0	0
Month 48-72: Romosozumab/Denosumab/Romosozumab/No Intervention	0	0
Month 48-72: Placebo/Placebo/Romosozumab/Zoledronic Acid	0	0
Month 48-72: Placebo/Denosumab/Romosozumab/Zoledronic Acid	0	0
Month 48-72: Romosozumab/Placebo/Romosozumab/Zoledronic Acid	0	0
Month 48-72: Romosozumab/Denosumab/Romosozumab/Zoledronic Acid	0	0

Primary outcome: Percent Change From Baseline at Month 12 in BMD at the Lumbar Spine

Time frame: Baseline to 12 months. Least squares mean (95% Confidence Interval). Unit: percent change

Measure	Placebo n = 47	Alendronate n = 47	Teriparatide n = 46	Romosozumab 70 mg QM n = 44	Romosozumab 140 mg Q3M n = 49	Romosozumab 140 mg QM n = 46	Romosozumab 210 mg Q3M n = 51	Romosozumab 210 mg QM n = 49	Romosozumab Monthly n = 139	Romosozumab Every 3 Months n = 100	Romosozumab 140 mg n = 95	Romosozumab 210 mg n = 100
Value	-0.1 (-1.2 to 0.9)	4.1 (3.0 to 5.1)	7.1 (6.1 to 8.2)	5.4 (4.3 to 6.4)	5.4 (4.4 to 6.5)	9.1 (8.0 to 10.2)	5.5 (4.4 to 6.6)	11.3 (10.3 to 12.4)	8.6 (7.9 to 9.3)	5.5 (4.7 to 6.3)	7.3 (6.4 to 8.1)	8.4 (7.6 to 9.2)

Placebo vs Romosozumab Monthly: LS Mean Difference from Placebo: 8.7 (95% CI 7.5 to 9.9), p < 0.0001, Linear Mixed Effects Model
Placebo vs Romosozumab Every 3 Months: LS Mean Difference from placebo: 5.6 (95% CI 4.3 to 6.9), p < 0.0001, Linear Mixed Effects Model
Placebo vs Romosozumab 140 mg: LS Mean Difference from Placebo: 7.4 (95% CI 6.1 to 8.7), p < 0.0001, Linear Mixed Effects Model

Population analysed: All randomized participants who had non-missing baseline and month 12 measurements.

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events are reported by treatment phase: Romosozumab treatment phase (Baseline [BL] to month 12 and 24); Denosumab extension phase (months 24 to 36); Romosozumab retreatment phase (months 36 to 48); Follow-on phase (months 48 to 72).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
BL-Month 12: Placebo QM	3 of 30 (10%)	25 of 30 (83.3%)	Not reported
BL-Month 12: Placebo Q3M	4 of 20 (20%)	19 of 20 (95%)	Not reported
BL-Month 12: Alendronate	4 of 51 (7.8%)	38 of 51 (74.5%)	Not reported
BL-Month12: Teriparatide	5 of 54 (9.3%)	36 of 54 (66.7%)	Not reported
BL-Month 12: Romosozumab 70 mg QM	5 of 50 (10%)	46 of 50 (92%)	Not reported
BL-Month 12: Romosozumab 140 mg Q3M	3 of 52 (5.8%)	40 of 52 (76.9%)	Not reported
BL-Month 12: Romosozumab 140 mg QM	2 of 49 (4.1%)	41 of 49 (83.7%)	Not reported
BL-Month 12: Romosozumab 210 mg Q3M	3 of 53 (5.7%)	45 of 53 (84.9%)	Not reported
BL-Month 12: Romosozumab 210 mg QM	6 of 51 (11.8%)	40 of 51 (78.4%)	Not reported
BL-Month 24: Placebo QM	5 of 30 (16.7%)	28 of 30 (93.3%)	Not reported
BL-Month 24: Placebo Q3M	4 of 20 (20%)	20 of 20 (100%)	Not reported
BL-Month 24: ALN/Romosozumab 140 mg QM	8 of 51 (15.7%)	49 of 51 (96.1%)	Not reported
BL-Month 24: Romosozumab 70 mg QM	9 of 50 (18%)	48 of 50 (96%)	Not reported
BL-Month 24: Romosozumab 140 mg Q3M	8 of 52 (15.4%)	47 of 52 (90.4%)	Not reported
BL-Month 24: Romosozumab 140 mg QM	8 of 49 (16.3%)	46 of 49 (93.9%)	Not reported
BL-Month 24: Romosozumab 210 mg Q3M	6 of 53 (11.3%)	51 of 53 (96.2%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 27487526Genant 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.
Background: PubMed 28543940Keaveny 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.
Background: PubMed 31628490Kendler 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.
Background: PubMed 29694685McClung 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.
Background: PubMed 32623487McClung 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.
Background: PubMed 34258507McClung 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.
Background: PubMed 34738660Poole 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.
Derived from this study: PubMed 24382002McClung 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.
AmgenTrials clinical trials websiteLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

MD study director

Amgen

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Alendronate, Teriparatide and Romosozumab in people with Low Bone Mineral Density and Postmenopausal Osteoporosis, run by Amgen.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline at Month 12 in BMD at the Lumbar Spine (time frame: Baseline to 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00896532, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2022.