NCT00896532

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.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
419

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jun 2009

Longer than P75 for phase_2

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 7, 2009

Completed
4 days until next milestone

First Posted

Study publicly available on registry

May 11, 2009

Completed
23 days until next milestone

Study Start

First participant enrolled

June 3, 2009

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 21, 2011

Completed
5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 18, 2016

Completed
2.8 years until next milestone

Results Posted

Study results publicly available

December 14, 2018

Completed
Last Updated

September 22, 2022

Status Verified

September 1, 2022

Enrollment Period

1.7 years

First QC Date

May 7, 2009

Results QC Date

November 20, 2018

Last Update Submit

September 9, 2022

Conditions

Low Bone Mineral DensityPostmenopausal Osteoporosis

Outcome Measures

Primary Outcomes (1)

  • 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.

    Baseline to 12 months

Secondary Outcomes (10)

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

    Baseline to 6 months

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

    Baseline to 6 months

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

    Baseline to 6 months

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

    Baseline to 12 months

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

    Baseline to 12 months

  • +5 more secondary outcomes

Study Arms (8)

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.

Drug: Placebo to RomosozumabDrug: DenosumabDrug: Placebo to DenosumabDrug: 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.

Drug: AlendronateDrug: RomosozumabDrug: DenosumabDrug: 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.

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.

Drug: RomosozumabDrug: DenosumabDrug: Placebo to DenosumabDrug: 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.

Drug: RomosozumabDrug: DenosumabDrug: Placebo to DenosumabDrug: 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.

Drug: RomosozumabDrug: DenosumabDrug: Placebo to DenosumabDrug: 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.

Drug: RomosozumabDrug: DenosumabDrug: Placebo to DenosumabDrug: 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.

Drug: RomosozumabDrug: DenosumabDrug: Placebo to DenosumabDrug: Zoledronic acid

Interventions

Placebo to RomosozumabDRUG

Administered by subcutaneous injection QM or Q3M.

Placebo
AlendronateDRUG

Administered orally once a week

Also known as: Fosamax
Alendronate
TeriparatideDRUG

Teriparatide 20 μg administered by subcutaneous injection once a day

Also known as: Forsteo
Teriparatide
RomosozumabDRUG

Administered by subcutaneous injection

Also known as: AMG 785, EVENITY™
AlendronateRomosozumab 140 mg Q3MRomosozumab 140 mg QMRomosozumab 210 mg Q3MRomosozumab 210 mg QMRomosozumab 70 mg QM
DenosumabDRUG

Denosumab 60 mg administered by subcutaneous injection Q6M

Also known as: Prolia®
AlendronatePlaceboRomosozumab 140 mg Q3MRomosozumab 140 mg QMRomosozumab 210 mg Q3MRomosozumab 210 mg QMRomosozumab 70 mg QM
Placebo to DenosumabDRUG

Administered by subcutaneous injection Q6M

AlendronatePlaceboRomosozumab 140 mg Q3MRomosozumab 140 mg QMRomosozumab 210 mg Q3MRomosozumab 210 mg QMRomosozumab 70 mg QM
Zoledronic acidDRUG

Zoledronic acid 5 mg administered intravenously

Also known as: Aclasta
PlaceboRomosozumab 140 mg Q3MRomosozumab 140 mg QMRomosozumab 210 mg Q3MRomosozumab 210 mg QMRomosozumab 70 mg QM

Eligibility Criteria

Age55 Years - 85 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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
  • \- Normocalcemia at or after the Month 21 visit but before the Month 24 study 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
  • 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
  • +17 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (8)

  • 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: 27487526BACKGROUND

  • 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: 28543940BACKGROUND

  • 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: 31628490BACKGROUND

  • 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: 29694685BACKGROUND

  • 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: 32623487BACKGROUND

  • 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: 34258507BACKGROUND

  • 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: 34738660BACKGROUND

  • 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.

    PMID: 24382002DERIVED

Related Links

MeSH Terms

Conditions

Bone Diseases, MetabolicOsteoporosis, Postmenopausal

Interventions

AlendronateTeriparatideromosozumabDenosumabZoledronic Acid

Condition Hierarchy (Ancestors)

Bone DiseasesMusculoskeletal DiseasesMetabolic DiseasesNutritional and Metabolic DiseasesOsteoporosis

Intervention Hierarchy (Ancestors)

DiphosphonatesOrganophosphonatesOrganophosphorus CompoundsOrganic ChemicalsParathyroid HormonePeptide HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsPeptidesAmino Acids, Peptides, and ProteinsAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsSerum GlobulinsGlobulinsImidazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Results Point of Contact

Title
Study Director
Organization
Amgen Inc.
866-572-6436

Study Officials

  • MD

    Amgen

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 7, 2009

First Posted

May 11, 2009

Study Start

June 3, 2009

Primary Completion

February 21, 2011

Study Completion

February 18, 2016

Last Updated

September 22, 2022

Results First Posted

December 14, 2018

Record last verified: 2022-09