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

Primary Purpose

Low Bone Mineral Density, Postmenopausal Osteoporosis

Status

Completed

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Placebo to Romosozumab

Alendronate

Teriparatide

Romosozumab

Denosumab

Placebo to Denosumab

Zoledronic acid

About this trial

This is an interventional treatment trial for Low Bone Mineral Density

Eligibility Criteria

55 Years - 85 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Placebo Comparator

Active Comparator

Experimental

Arm Label

Placebo

Alendronate

Teriparatide

Romosozumab 70 mg QM

Romosozumab 140 mg Q3M

Romosozumab 140 mg QM

Romosozumab 210 mg Q3M

Romosozumab 210 mg QM

Arm Description

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.

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.

Participants received open-label teriparatide 20 μg subcutaneously every day (QD) for 12 months. At month 12 participants ended study participation.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Percent Change From Baseline at Month 6 in BMD of the Total Hip

Percent Change From Baseline at Month 6 in BMD of the Femoral Neck

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.

Percent Change From Baseline at Month 12 in BMD of the Femoral Neck

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT00896532

First Posted

May 7, 2009

Last Updated

September 9, 2022

Sponsor

Amgen

1. Study Identification

Unique Protocol Identification Number

NCT00896532

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Completed

Study Start Date

June 3, 2009 (Actual)

Primary Completion Date

February 21, 2011 (Actual)

Study Completion Date

February 18, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Amgen

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Low Bone Mineral Density, Postmenopausal Osteoporosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

419 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Arm Title

Alendronate

Arm Type

Active Comparator

Arm Description

Arm Title

Teriparatide

Arm Type

Active Comparator

Arm Description

Participants received open-label teriparatide 20 μg subcutaneously every day (QD) for 12 months. At month 12 participants ended study participation.

Arm Title

Romosozumab 70 mg QM

Arm Type

Experimental

Arm Description

Arm Title

Romosozumab 140 mg Q3M

Arm Type

Experimental

Arm Description

Arm Title

Romosozumab 140 mg QM

Arm Type

Experimental

Arm Description

Arm Title

Romosozumab 210 mg Q3M

Arm Type

Experimental

Arm Description

Arm Title

Romosozumab 210 mg QM

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Placebo to Romosozumab

Intervention Description

Administered by subcutaneous injection QM or Q3M.

Intervention Type

Drug

Intervention Name(s)

Alendronate

Other Intervention Name(s)

Fosamax

Intervention Description

Administered orally once a week

Intervention Type

Drug

Intervention Name(s)

Teriparatide

Other Intervention Name(s)

Forsteo

Intervention Description

Teriparatide 20 μg administered by subcutaneous injection once a day

Intervention Type

Drug

Intervention Name(s)

Romosozumab

Other Intervention Name(s)

AMG 785, EVENITY™

Intervention Description

Administered by subcutaneous injection

Intervention Type

Drug

Intervention Name(s)

Denosumab

Other Intervention Name(s)

Prolia®

Intervention Description

Denosumab 60 mg administered by subcutaneous injection Q6M

Intervention Type

Drug

Intervention Name(s)

Placebo to Denosumab

Intervention Description

Administered by subcutaneous injection Q6M

Intervention Type

Drug

Intervention Name(s)

Zoledronic acid

Other Intervention Name(s)

Aclasta

Intervention Description

Zoledronic acid 5 mg administered intravenously

Primary Outcome Measure Information:

Title

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

Description

Bone mineral density was measured using dual energy x-ray absorptiometry (DXA). Images were analyzed by a central imaging reader.

Time Frame

Baseline to 12 months

Secondary Outcome Measure Information:

Title

Percent Change From Baseline at Month 6 in BMD at the Lumbar Spine

Description

Time Frame

Baseline to 6 months

Title

Percent Change From Baseline at Month 6 in BMD of the Total Hip

Description

Time Frame

Baseline to 6 months

Title

Percent Change From Baseline at Month 6 in BMD of the Femoral Neck

Description

Time Frame

Baseline to 6 months

Title

Percent Change From Baseline at Month 12 in BMD of the Total Hip

Description

Time Frame

Baseline to 12 months

Title

Percent Change From Baseline at Month 12 in BMD of the Femoral Neck

Description

Time Frame

Baseline to 12 months

Title

Percent Change From Baseline at Month 12 in BMD of the Distal Radius

Description

Time Frame

Baseline to 12 months

Title

Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP)

Description

Time Frame

Baseline and months 1, 3, 6, 9, and 12

Title

Percent Change From Baseline in Type 1 Collagen C-telopeptide (CTX)

Description

Time Frame

Baseline and months 1, 3, 6, 9, and 12

Title

Percent Change From Baseline in Osteocalcin

Description

Time Frame

Baseline and months 1, 3, 6, 9, and 12

Title

Percent Change From Baseline in Bone-specific Alkaline Phosphatase (BSAP)

Description

Time Frame

Baseline and months 1, 3, 6, 9, and 12

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

55 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Organizational Affiliation

Amgen

Official's Role

Study Director

12. IPD Sharing Statement

Citations:

PubMed Identifier

27487526

Citation

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.

Results Reference

background

PubMed Identifier

28543940

Citation

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.

Results Reference

background

PubMed Identifier

31628490

Citation

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.

Results Reference

background

PubMed Identifier

29694685

Citation

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.

Results Reference

background

PubMed Identifier

32623487

Citation

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.

Results Reference

background

PubMed Identifier

34258507

Citation

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.

Results Reference

background

PubMed Identifier

34738660

Citation

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.

Results Reference

background

PubMed Identifier

24382002

Citation

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.

Results Reference

derived

Links:

URL

http://www.amgentrials.com

Description

AmgenTrials clinical trials website

Learn more about this trial

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

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