Efficacy and Safety of Denosumab Compared With Risedronate in Individuals Taking Glucocorticoids (GIOP)

A Randomized, Double-blind, Active-controlled Study to Evaluate the Efficacy and Safety of Denosumab Compared With Risedronate in Glucocorticoid-treated Individuals

This is a 2-year study to evaluate the effect of denosumab versus risedronate in adults with glucocorticoid-induced osteoporosis.

Study Overview

• Status: Completed
• Conditions: Steroid-induced Osteopor, Glucocorticoid-induced Ostepor
• Intervention / Treatment: Drug: Denosumab; Drug: Placebo for risendronate; Drug: Risendronate; Drug: Placebo for denosumab

• Study Type: Interventional
• Enrollment (Actual): 795
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1431FBO
    • Research Site
  • Buenos Aires
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1128AAF
      • Research Site
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, 1114
      • Research Site
• Belgium
  • Bruxelles, Belgium, 1200
    • Research Site
  • Genk, Belgium, 3600
    • Research Site
  • Gent, Belgium, 9000
    • Research Site
  • Liege, Belgium, 4000
    • Research Site
  • Wilrijk, Belgium, 2610
    • Research Site
• Canada
  • Quebec, Canada, G1V 3M7
    • Research Site
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E1
      • Research Site
  • Ontario
    • Barrie, Ontario, Canada, L4M 6L2
      • Research Site
    • Hamilton, Ontario, Canada, L8N 1Y2
      • Research Site
    • Waterloo, Ontario, Canada, N2J 1C4
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H2L 1S6
      • Research Site
    • Montreal, Quebec, Canada, H3Z 2Z3
      • Research Site
    • Trois-Rivieres, Quebec, Canada, G8Z 1Y2
      • Research Site
    • Westmout, Quebec, Canada, H3Z 1E5
      • Research Site
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7K 0H6
      • Research Site
• Colombia
  • Atlántico
    • Barranquilla, Atlántico, Colombia, 08001000
      • Research Site
• Czechia
  • Brno, Czechia, 602 00
    • Research Site
  • Pardubice, Czechia, 530 02
    • Research Site
  • Plzen, Czechia, 305 99
    • Research Site
  • Praha 11 - Chodov, Czechia, 148 00
    • Research Site
  • Praha 2, Czechia, 128 50
    • Research Site
  • Praha 3, Czechia, 130 00
    • Research Site
  • Uherske Hradiste, Czechia, 686 01
    • Research Site
• Denmark
  • Aalborg, Denmark, 9000
    • Research Site
  • Ballerup, Denmark, 2750
    • Research Site
  • Vejle, Denmark, 7100
    • Research Site
  • Århus C, Denmark, 8000
    • Research Site
• France
  • Lyon Cédex 3, France, 69437
    • Research Site
  • Orleans Cedex, France, 45067
    • Research Site
  • Vandoeuvre les Nancy, France, 54511
    • Research Site
• Germany
  • Bad Nauheim, Germany, 61231
    • Research Site
  • Bad Reichenhall, Germany, 83435
    • Research Site
  • Berlin, Germany, 10117
    • Research Site
  • Hildesheim, Germany, 31134
    • Research Site
  • Köln, Germany, 50937
    • Research Site
  • Vogelsang-Gommern, Germany, 39245
    • Research Site
• Hungary
  • Budapest, Hungary, 1036
    • Research Site
  • Budapest, Hungary, 1023
    • Research Site
  • Debrecen, Hungary, 4032
    • Research Site
  • Gyula, Hungary, 5700
    • Research Site
  • Szeged, Hungary, 6720
    • Research Site
  • Szikszo, Hungary, 3800
    • Research Site
• Korea, Republic of
  • Daegu, Korea, Republic of, 700-712
    • Research Site
  • Daejeon, Korea, Republic of, 301-721
    • Research Site
  • Gwangju, Korea, Republic of, 501-757
    • Research Site
  • Jinju-si, Korea, Republic of, 660-702
    • Research Site
  • Seoul, Korea, Republic of, 150-713
    • Research Site
  • Seoul, Korea, Republic of, 120-752
    • Research Site
  • Seoul, Korea, Republic of, 137-701
    • Research Site
• Mexico
  • Distrito Federal
    • Mexico, Distrito Federal, Mexico, 06100
      • Research Site
  • Guanajuato
    • Leon, Guanajuato, Mexico, 37000
      • Research Site
  • Michoacán
    • Morelia, Michoacán, Mexico, 58070
      • Research Site
  • San Luis Potosí
    • San Luis Potosi, San Luis Potosí, Mexico, 78200
      • Research Site
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Research Site
  • Helmond, Netherlands, 5707 HA
    • Research Site
  • Utrecht, Netherlands, 3584 XC
    • Research Site
• Poland
  • Bialystok, Poland, 15-879
    • Research Site
  • Kraków, Poland, 31-501
    • Research Site
  • Lodz, Poland, 90-368
    • Research Site
  • Poznan, Poland, 60-356
    • Research Site
  • Poznan, Poland, 60-218
    • Research Site
  • Stalowa Wola, Poland, 37-450
    • Research Site
  • Torun, Poland, 87-100
    • Research Site
  • Warszawa, Poland, 01-192
    • Research Site
  • Warszawa, Poland, 04-730
    • Research Site
  • Wroclaw, Poland, 51-124
    • Research Site
• Russian Federation
  • Ekaterinburg, Russian Federation, 620102
    • Research Site
  • Moscow, Russian Federation, 115522
    • Research Site
  • Moscow, Russian Federation, 105077
    • Research Site
  • Nizhniy Novgorod, Russian Federation, 603155
    • Research Site
  • Saint Petersburg, Russian Federation, 194291
    • Research Site
  • Saint Petersburg, Russian Federation, 190103
    • Research Site
  • Saint-Petersburg, Russian Federation, 190068
    • Research Site
  • Yaroslavl, Russian Federation, 150003
    • Research Site
• Spain
  • Madrid, Spain, 28046
    • Research Site
  • Madrid, Spain, 28006
    • Research Site
  • Cataluña
    • Barcelona, Cataluña, Spain, 08041
      • Research Site
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46026
      • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Research Site
  • California
    • Sacramento, California, United States, 95817
      • Research Site
  • Colorado
    • Lakewood, Colorado, United States, 80227
      • Research Site
  • Florida
    • Pembroke Pines, Florida, United States, 33029
      • Research Site
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Research Site
    • Evanston, Illinois, United States, 60201
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Research Site
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Research Site
    • Cumberland, Maryland, United States, 21502
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Research Site
  • Michigan
    • Detroit, Michigan, United States, 48236
      • Research Site
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Research Site
    • Fargo, North Dakota, United States, 58103
      • Research Site
  • Ohio
    • Mayfield, Ohio, United States, 44143
      • Research Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Research Site
    • Wyomissing, Pennsylvania, United States, 19610
      • Research Site
  • West Virginia
    • Beckley, West Virginia, United States, 25801
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Men and women 18 years of age or older who have been taking glucocorticoid treatment. Men and women who are less than 50 years of age must have had a fracture as an adult to be eligible. Men and women who are 50 years of age or older who have been taking glucocorticoids must meet protocol-specific BMD criteria.

Exclusion Criteria:

Use of agents affecting bone metabolism, use of more than one biologic agent for inflammatory disease, history of bone disease (except osteoporosis), low vitamin D level (one can enter the trial after vitamin D levels are corrected), abnormalities of blood calcium, an underactive or overactive thyroid condition that is not treated and stable, Addison's disease, any abnormality of the parathyroid glands (the glands that control blood calcium), currently pregnant or planning a pregnancy, currently breast feeding, and other criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Denosumab; Participants received 60 mg denosumab by subcutaneous injection on day 1 and at months 6, 12, and 18. Participants also received placebo to risedronate orally once a day for 24 months.	Drug: Denosumab; Administered by subcutaneous injection once every 6 months; Other Names: Prolia®; Drug: Placebo for risendronate; Administered orally once a day
Experimental: Risendronate; Participants received 5 mg risedronate orally once a day for 24 months and placebo to densumab by subcutaneous injection on day 1 and at months 6, 12, and 18.	Drug: Risendronate; Administered orally once a day; Other Names: Actonel, Atelvia; Drug: Placebo for denosumab; Administered by subcutaneous injection once every 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 (Non-inferiority Analysis)	Bone mineral density at the lumbar spine was measured by dual-energy x-ray absorptiometry (DXA).	Baseline and month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 (Superiority Analysis)	Bone mineral density at the lumbar spine was measured by dual-energy x-ray absorptiometry (DXA).	Baseline and month 12
Percent Change From Baseline in Total Hip Bone Mineral Density at Month 12	Bone mineral density at the total hip was measured by dual-energy x-ray absorptiometry (DXA).	Baseline and month 12
Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 24	Bone mineral density at the lumbar spine was measured by dual-energy x-ray absorptiometry (DXA).	Baseline and month 24
Percent Change From Baseline in Total Hip Bone Mineral Density at Month 24	Bone mineral density at the total hip was measured by dual-energy x-ray absorptiometry (DXA).	Baseline and month 24

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Saag KG, Wagman RB, Geusens P, Adachi JD, Messina OD, Emkey R, Chapurlat R, Wang A, Pannacciulli N, Lems WF. Denosumab versus risedronate in glucocorticoid-induced osteoporosis: a multicentre, randomised, double-blind, active-controlled, double-dummy, non-inferiority study. Lancet Diabetes Endocrinol. 2018 Jun;6(6):445-454. doi: 10.1016/S2213-8587(18)30075-5. Epub 2018 Apr 6.
• Saag KG, Pannacciulli N, Geusens P, Adachi JD, Messina OD, Morales-Torres J, Emkey R, Butler PW, Yin X, Lems WF. Denosumab Versus Risedronate in Glucocorticoid-Induced Osteoporosis: Final Results of a Twenty-Four-Month Randomized, Double-Blind, Double-Dummy Trial. Arthritis Rheumatol. 2019 Jul;71(7):1174-1184. doi: 10.1002/art.40874. Epub 2019 May 25.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2012
• Primary Completion (Actual): June 21, 2016
• Study Completion (Actual): June 29, 2017

Study Registration Dates

• First Submitted: April 10, 2012
• First Submitted That Met QC Criteria: April 11, 2012
• First Posted (Estimate): April 12, 2012

Study Record Updates

• Last Update Posted (Actual): July 27, 2018
• Last Update Submitted That Met QC Criteria: July 2, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: GIOP, Glucocorticoid, osteporosis, denosumab, BMD, Bone Mineral Density
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: 20101217; 2010-024393-19 (EudraCT Number)