Study to Determine the Efficacy and Safety of Romosozumab in the Treatment of Postmenopausal Women With Osteoporosis

NCT ID: NCT01631214

Last Updated: 2025-02-21

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

4093 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-05-04

Study Completion Date

2017-06-29

Brief Summary

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The purpose of this study is to determine if treatment is effective in preventing fractures in women with postmenopausal osteoporosis.

Detailed Description

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In this trial, women were randomly assigned in a 1:1 ratio to receive monthly subcutaneous romosozumab or weekly oral alendronate for 12 months. Randomization was stratified according to age (\<75 vs. ≥75 years). After completion of the double-blind treatment period, all the participants were to receive open-label weekly oral alendronate until the end of the trial, with blinding to the initial treatment assignment maintained.

The primary analysis was performed when clinical fracture events had been confirmed in at least 330 participants and all the participants had completed the month 24 visit. The study was to continue in an event-driven manner until at least 440 participants experienced a nonvertebral fracture or if the superiority of romosozumab was proven for nonvertebral fractures at the primary analysis.

Conditions

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Postmenopausal Women With Osteoporosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Alendronate/Alendronate

Participants received 70 mg alendronate once a week and placebo to romosozumab subcutaneously once a month for the first 12 months. After completion of the 12-month double-blind treatment period participants continued to receive 70 mg alendronate once a week until the end of the study.

Group Type ACTIVE_COMPARATOR

Alendronate

Intervention Type DRUG

Alendronate 70 mg tablet taken once a week

Placebo to Romosozumab

Intervention Type DRUG

Administered by subcutaneous injection once a month during the double-blind treatment phase.

Romosozumab/Alendronate

Participants received 210 mg romosozumab subcutaneously once a month and placebo to alendronate orally once a week for the first 12 months. After completion of the 12-month double-blind treatment period participants received 70 mg alendronate once a week until the end of the study.

Group Type EXPERIMENTAL

Romosozumab

Intervention Type BIOLOGICAL

Romosozumab 210 mg administered by subcutaneous injection once a month during the double-blind treatment phase.

Alendronate

Intervention Type DRUG

Alendronate 70 mg tablet taken once a week

Placebo to Alendronate

Intervention Type DRUG

Matching placebo tablet taken once a week during the double-blind treatment phase.

Interventions

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Romosozumab

Romosozumab 210 mg administered by subcutaneous injection once a month during the double-blind treatment phase.

Intervention Type BIOLOGICAL

Alendronate

Alendronate 70 mg tablet taken once a week

Intervention Type DRUG

Placebo to Romosozumab

Administered by subcutaneous injection once a month during the double-blind treatment phase.

Intervention Type DRUG

Placebo to Alendronate

Matching placebo tablet taken once a week during the double-blind treatment phase.

Intervention Type DRUG

Other Intervention Names

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AMG 785 Evenity Fosamax

Eligibility Criteria

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Inclusion Criteria

Postmenopausal women who meet at least one of the following bone mineral density (BMD) and fracture criteria:

* BMD T-score at the total hip or femoral neck of ≤ -2.50 and EITHER:

* at least 1 moderate (semiquantitative grade \[SQ\]2) or severe (SQ3) vertebral fracture OR
* at least 2 mild (SQ1) vertebral fractures OR
* BMD T-score at the total hip or femoral neck of ≤ -2.00 and EITHER:

* at least 2 moderate (SQ2) or severe (SQ3) vertebral fractures OR
* a fracture of the proximal femur that occurred within 3 to 24 months prior to randomization.

Exclusion Criteria

* History of metabolic or bone disease (except osteoporosis)
* Use of agents affecting bone metabolism
* Vitamin D insufficiency
* History of solid organ or bone marrow transplants
* Hyper- or hypocalcemia
* Hyper- or hypothyroidism
* Hyper- or hypoparathyroidism
* Possible signs of intolerance to alendronate
Minimum Eligible Age

55 Years

Maximum Eligible Age

90 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

Locations

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Hamburg, , Germany

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Hanover, , Germany

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Heinsberg, , Germany

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Birmingham, Alabama, United States

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Peoria, Arizona, United States

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Phoenix, Arizona, United States

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Scottsdale, Arizona, United States

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Downey, California, United States

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Greenbrae, California, United States

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Los Angeles, California, United States

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South Lake Tahoe, California, United States

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Tustin, California, United States

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Walnut Creek, California, United States

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Lakewood, Colorado, United States

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Fort Lauderdale, Florida, United States

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Miami, Florida, United States

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Stuart, Florida, United States

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West Palm Beach, Florida, United States

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Gainesville, Georgia, United States

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Maywood, Illinois, United States

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Quincy, Illinois, United States

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Indianapolis, Indiana, United States

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Bethesda, Maryland, United States

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Boston, Massachusetts, United States

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Detroit, Michigan, United States

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St Louis, Missouri, United States

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Las Vegas, Nevada, United States

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Las Cruces, New Mexico, United States

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Great Neck, New York, United States

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Bismarck, North Dakota, United States

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Pittsburgh, Pennsylvania, United States

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Wyomissing, Pennsylvania, United States

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Richmond, Virginia, United States

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Port Angeles, Washington, United States

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Madison, Wisconsin, United States

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Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

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Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

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Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

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Mar del Plata, Buenos Aires, Argentina

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Quilmes, Buenos Aires, Argentina

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Córdoba, Córdoba Province, Argentina

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Buenos Aires, , Argentina

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Darlinghurst, New South Wales, Australia

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Kogarah, New South Wales, Australia

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Randwick, New South Wales, Australia

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Box Hill, Victoria, Australia

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Geelong, Victoria, Australia

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Heidelberg West, Victoria, Australia

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Parkville, Victoria, Australia

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Graz, , Austria

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Linz, , Austria

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Vienna, , Austria

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Bruges, , Belgium

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Brussels, , Belgium

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Genk, , Belgium

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Ghent, , Belgium

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Leuven, , Belgium

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Liège, , Belgium

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Fortaleza, Ceará, Brazil

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Vitória, Espírito Santo, Brazil

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Brasília, Federal District, Brazil

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Goiânia, Goiás, Brazil

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Curitiba, Paraná, Brazil

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Recife, Pernambuco, Brazil

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Rio de Janeiro, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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Plovdiv, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Vancouver, British Columbia, Canada

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Winnipeg, Manitoba, Canada

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St. John's, Newfoundland and Labrador, Canada

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Halifax, Nova Scotia, Canada

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Kitchener, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Trois-Rivières, Quebec, Canada

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Westmout, Quebec, Canada

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Santiago, , Chile

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Medellín, Antioquia, Colombia

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Barranquilla, Atlántico, Colombia

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Bogota, Cundinamarca, Colombia

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Bogota, Cundinamarca, Colombia

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Bogota, Cundinamarca, Colombia

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Bogotá, , Colombia

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Bucaramanga, , Colombia

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Brno, , Czechia

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Hradec Králové, , Czechia

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Klatovy, , Czechia

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Opava, , Czechia

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Ostrava-Trebovice, , Czechia

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Pardubice, , Czechia

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Pilsen, , Czechia

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Prague, , Czechia

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Prague, , Czechia

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Uherské Hradiště, , Czechia

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Zlín, , Czechia

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Aalborg, , Denmark

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Århus C, , Denmark

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Ballerup Municipality, , Denmark

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Glostrup Municipality, , Denmark

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Hvidovre, , Denmark

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Køge, , Denmark

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Odense, , Denmark

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Vejle, , Denmark

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Santo Domingo, Nacional, Dominican Republic

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Santo Domingo, Nacional, Dominican Republic

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Santiago de los Caballeros, Santiago Province, Dominican Republic

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Santo Domingo, , Dominican Republic

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Tallinn, , Estonia

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Tartu, , Estonia

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Helsinki, , Finland

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Jyväskylä, , Finland

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Kuopio, , Finland

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Turku, , Finland

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Bordeaux, , France

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Cahors, , France

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Lille, , France

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Lyon Cédex 3, , France

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Orléans, , France

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Saint-Priest-en-Jarez, , France

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Toulouse, , France

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Vandœuvre-lès-Nancy, , France

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Berlin, , Germany

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Bonn, , Germany

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Dresden, , Germany

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Frankfurt am Main, , Germany

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Frankfurt am Main, , Germany

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Freiburg im Breisgau, , Germany

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Hellersdorf, , Germany

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Leipzig, , Germany

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Magdeburg, , Germany

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Marburg, , Germany

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München, , Germany

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Würzburg, , Germany

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Athens, , Greece

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Athens, , Greece

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Athens, , Greece

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Athens, , Greece

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Athens, , Greece

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Larissa, , Greece

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Thessaloniki, , Greece

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Thessaloniki, , Greece

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Thessaloniki, , Greece

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Antigua Guatemala, Departamento de Sacatepéquez, Guatemala

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Guatemala City, , Guatemala

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Guatemala City, , Guatemala

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Guatemala City, , Guatemala

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Guatemala City, , Guatemala

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Guatemala City, , Guatemala

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Guatemala City, , Guatemala

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Guatemala City, , Guatemala

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Guatemala City, , Guatemala

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Hong Kong, , Hong Kong

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New Territories, , Hong Kong

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Balatonfüred, , Hungary

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Békéscsaba, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Debrecen, , Hungary

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Győr, , Hungary

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Kaposvár, , Hungary

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Kiskunhalas, , Hungary

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Kistarcsa, , Hungary

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Veszprém, , Hungary

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Zalaegerszeg, , Hungary

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Cork, , Ireland

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Dublin, , Ireland

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Galway, , Ireland

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Bnei Brak, , Israel

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Haifa, , Israel

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Jerusalem, , Israel

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Jerusalem, , Israel

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Tel Aviv, , Israel

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Arenzano GE, , Italy

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Bologna, , Italy

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Catania, , Italy

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Florence, , Italy

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Milan, , Italy

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Pisa, , Italy

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Pisa, , Italy

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Roma, , Italy

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Siena, , Italy

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Torino, , Italy

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Verona, , Italy

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Verona, , Italy

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Liepāja, , Latvia

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Riga, , Latvia

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Riga, , Latvia

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Vilnius, , Lithuania

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Vilnius, , Lithuania

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Mexicali, Baja California Norte, Mexico

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Mexicalli, Baja California Norte, Mexico

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León, Guanajuato, Mexico

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León, Guanajuato, Mexico

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Mexico City, Mexico City, Mexico

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Mexico City, Mexico City, Mexico

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Monterrey, Nuevo León, Mexico

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Querétaro City, Querétaro, Mexico

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Ciudad Obregón, Sonora, Mexico

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Leiden, , Netherlands

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Rotterdam, , Netherlands

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Venlo, , Netherlands

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Christchurch, , New Zealand

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Grafton, Auckland, , New Zealand

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Elverum, , Norway

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Hamar, , Norway

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Oslo, , Norway

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Stavanger, , Norway

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Bialystok, , Poland

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Bialystok, , Poland

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Dabrowka Dopiewo, , Poland

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Elblag, , Poland

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Gdynia, , Poland

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Gliwice, , Poland

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Katowice, , Poland

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Kielce, , Poland

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Krakow, , Poland

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Krakow, , Poland

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Lodz, , Poland

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Lodz, , Poland

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Poznan, , Poland

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Poznan, , Poland

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Świdnik, , Poland

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Torun, , Poland

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Warsaw, , Poland

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Warsaw, , Poland

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Warsaw, , Poland

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Wroclaw, , Poland

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Wroclaw, , Poland

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Wroclaw, , Poland

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Bucharest, , Romania

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Bucharest, , Romania

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Bucharest, , Romania

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Bucharest, , Romania

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Oradea, , Romania

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Târgu Mureş, , Romania

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Arkhangelsk, , Russia

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Ivanovo, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Nizhny Novgorod, , Russia

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Petrozavodsk, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Yaroslavl, , Russia

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Yekaterinburg, , Russia

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Banská Bystrica, , Slovakia

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Bratislava, , Slovakia

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Bratislava, , Slovakia

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Kosice-Saca, , Slovakia

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Lučenec, , Slovakia

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Piešťany, , Slovakia

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Trenčín, , Slovakia

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Johannesburg, Gauteng, South Africa

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Pretoria, Gauteng, South Africa

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Pretoria, Gauteng, South Africa

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Parow, Western Cape, South Africa

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Somerset West, Western Cape, South Africa

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Tygerberg, , South Africa

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Daegu, , South Korea

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Guri-si, , South Korea

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Gwangju, , South Korea

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Incheon, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Suwon-si, Gyeonggi-do, , South Korea

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Granada, Andalusia, Spain

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Seville, Andalusia, Spain

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Santander, Cantabria, Spain

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Barcelona, Catalonia, Spain

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Sant Joan Despí, Catalonia, Spain

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A Coruña, Galicia, Spain

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Madrid, , Spain

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Madrid, , Spain

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Linköping, , Sweden

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Mölndal, , Sweden

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Stockholm, , Sweden

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Umeå, , Sweden

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Tainan City, , Taiwan

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Taipei, , Taiwan

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Adana, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Birmingham, , United Kingdom

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Cambridge, , United Kingdom

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Cardiff, , United Kingdom

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Chorley, , United Kingdom

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Edinburgh, , United Kingdom

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Glasgow, , United Kingdom

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Liverpool, , United Kingdom

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Manchester, , United Kingdom

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Northwood, , United Kingdom

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Norwich, , United Kingdom

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Reading, , United Kingdom

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Sheffield, , United Kingdom

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Sidcup, , United Kingdom

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Staffordshire, , United Kingdom

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Warwick, , United Kingdom

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Countries

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United States Argentina Australia Austria Belgium Brazil Bulgaria Canada Chile Colombia Czechia Denmark Dominican Republic Estonia Finland France Germany Greece Guatemala Hong Kong Hungary Ireland Israel Italy Latvia Lithuania Mexico Netherlands New Zealand Norway Peru Poland Romania Russia Slovakia South Africa South Korea Spain Sweden Taiwan Turkey (Türkiye) United Kingdom

References

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Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, Maddox J, Fan M, Meisner PD, Grauer A. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. N Engl J Med. 2017 Oct 12;377(15):1417-1427. doi: 10.1056/NEJMoa1708322. Epub 2017 Sep 11.

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Cosman F, Lewiecki EM, Ebeling PR, Hesse E, Napoli N, Matsumoto T, Crittenden DB, Rojeski M, Yang W, Libanati C, Ferrari S. T-Score as an Indicator of Fracture Risk During Treatment With Romosozumab or Alendronate in the ARCH Trial. J Bone Miner Res. 2020 Jul;35(7):1333-1342. doi: 10.1002/jbmr.3996. Epub 2020 May 22.

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Lau EMC, Dinavahi R, Woo YC, Wu CH, Guan J, Maddox J, Tolman C, Yang W, Shin CS. Romosozumab or alendronate for fracture prevention in East Asian patients: a subanalysis of the phase III, randomized ARCH study. Osteoporos Int. 2020 Apr;31(4):677-685. doi: 10.1007/s00198-020-05324-0. Epub 2020 Feb 11.

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Miller PD, Adachi JD, Albergaria BH, Cheung AM, Chines AA, Gielen E, Langdahl BL, Miyauchi A, Oates M, Reid IR, Santiago NR, Vanderkelen M, Wang Z, Yu Z. Efficacy and Safety of Romosozumab Among Postmenopausal Women With Osteoporosis and Mild-to-Moderate Chronic Kidney Disease. J Bone Miner Res. 2022 Aug;37(8):1437-1445. doi: 10.1002/jbmr.4563. Epub 2022 May 20.

Reference Type BACKGROUND
PMID: 35466448 (View on PubMed)

Brown JP, Engelke K, Keaveny TM, Chines A, Chapurlat R, Foldes AJ, Nogues X, Civitelli R, De Villiers T, Massari F, Zerbini CAF, Wang Z, Oates MK, Recknor C, Libanati C. Romosozumab improves lumbar spine bone mass and bone strength parameters relative to alendronate in postmenopausal women: results from the Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH) trial. J Bone Miner Res. 2021 Nov;36(11):2139-2152. doi: 10.1002/jbmr.4409. Epub 2021 Aug 10.

Reference Type BACKGROUND
PMID: 34190361 (View on PubMed)

McClung MR, Betah D, Leder BZ, Kendler DL, Oates M, Timoshanko J, Wang Z. Romosozumab improves microarchitecture as assessed by tissue thickness-adjusted trabecular bone score in postmenopausal women with osteoporosis. J Bone Miner Res. 2025 Feb 2;40(2):193-200. doi: 10.1093/jbmr/zjae194.

Reference Type BACKGROUND
PMID: 39656908 (View on PubMed)

Ferrari S, Betah D, Feldman RG, Langdahl BL, Oates M, Timoshanko J, Wang Z, Dhaliwal R. Romosozumab Improves Tissue Thickness-Adjusted Trabecular Bone Score in Women With Osteoporosis and Diabetes. J Clin Endocrinol Metab. 2025 Sep 16;110(10):2861-2868. doi: 10.1210/clinem/dgae862.

Reference Type BACKGROUND
PMID: 39854280 (View on PubMed)

Lane J, Langdahl B, Stone M, Kurth A, Oates M, Timoshanko J, Wang Z, Libanati C, Cosman F. Romosozumab in patients who experienced an on-study fracture: post hoc analyses of the FRAME and ARCH phase 3 trials. Osteoporos Int. 2024 Jul;35(7):1195-1204. doi: 10.1007/s00198-024-07049-w. Epub 2024 Apr 4.

Reference Type DERIVED
PMID: 38573517 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

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2011-003142-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20110142

Identifier Type: -

Identifier Source: org_study_id

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