A Study to Evaluate Denosumab in the Treatment of Postmenopausal Osteoporosis

NCT00089791 | Completed Phase 3 Results DMC

• 1 other identifier: 20030216
• Study Type: interventional
• Target: 7,808
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will evaluate the effectiveness and safety of denosumab in treating women with Postmenopausal Osteoporosis.

Conditions

Osteoporosis

Keywords

Postmenopausal Osteoporosis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With New Vertebral Fractures

  A new vertebral fracture, assessed by lateral spine X-ray using Genant semiquantitative scoring method, was identified as an ≥ 1 grade increase from the Baseline grade of 0 in any vertebra from T4 to L4. New vertebral fractures included morphometric vertebral fractures (assessed at scheduled visits and not associated with signs or symptoms \[or both\] indicative of a fracture) and clinical vertebral fractures (assessed at either a scheduled or unscheduled visit and associated with any signs and/or symptoms indicative of a fracture, excluding any fracture associated with high trauma severity or a pathologic fracture).

  36 months

Secondary Outcomes (2)

• Number of Participants With Nonvertebral Fractures

  36 months

• Number of Participants With a Hip Fracture

  36 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo administered subcutaneously once every 6 months for 3 years.

Drug: placebo

Denosumab 60 mg Q6M

EXPERIMENTAL

Denosumab 60 mg administered subcutaneously once every 6 months (Q6M) for 3 years.

Drug: Denosumab

Interventions

placebo DRUG

Placebo administered by subcutaneous injection

Placebo

Denosumab DRUG

Denosumab 60 mg administered by subcutaneous injection

Also known as: AMG 162, Prolia®

Denosumab 60 mg Q6M

Eligibility Criteria

• Age: 60 Years - 90 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women who are 60 to 90 years of age may be eligible to participate
• Bone mineral density (BMD) T-Score at hip or spine must be less than -2.5

You may not qualify if:

• BMD T-Score at the hip or the spine of less than -4.0
• Patients with any severe or more than two moderate vertebral fractures on spinal x-ray at entry

Sponsors & Collaborators

• Amgen: lead

Related Publications (33)

• Adami S, Libanati C, Boonen S, Cummings SR, Ho PR, Wang A, Siris E, Lane J; FREEDOM Fracture-Healing Writing Group; Adachi JD, Bhandari M, de Gregorio L, Gilchrist N, Lyritis G, Moller G, Palacios S, Pavelka K, Heinrich R, Roux C, Uebelhart D. Denosumab treatment in postmenopausal women with osteoporosis does not interfere with fracture-healing: results from the FREEDOM trial. J Bone Joint Surg Am. 2012 Dec 5;94(23):2113-9. doi: 10.2106/JBJS.K.00774.

  PMID: 23097066 BACKGROUND

• Austin M, Yang YC, Vittinghoff E, Adami S, Boonen S, Bauer DC, Bianchi G, Bolognese MA, Christiansen C, Eastell R, Grauer A, Hawkins F, Kendler DL, Oliveri B, McClung MR, Reid IR, Siris ES, Zanchetta J, Zerbini CA, Libanati C, Cummings SR; FREEDOM Trial. Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fractures. J Bone Miner Res. 2012 Mar;27(3):687-93. doi: 10.1002/jbmr.1472.

  PMID: 22095631 BACKGROUND

• Bolognese MA, Teglbjaerg CS, Zanchetta JR, Lippuner K, McClung MR, Brandi ML, Hoiseth A, Lakatos P, Moffett AH, Lorenc RS, Wang A, Libanati C. Denosumab significantly increases DXA BMD at both trabecular and cortical sites: results from the FREEDOM study. J Clin Densitom. 2013 Apr-Jun;16(2):147-53. doi: 10.1016/j.jocd.2012.02.006. Epub 2012 Apr 20.

  PMID: 22521543 BACKGROUND

• Boonen S, Adachi JD, Man Z, Cummings SR, Lippuner K, Torring O, Gallagher JC, Farrerons J, Wang A, Franchimont N, San Martin J, Grauer A, McClung M. Treatment with denosumab reduces the incidence of new vertebral and hip fractures in postmenopausal women at high risk. J Clin Endocrinol Metab. 2011 Jun;96(6):1727-36. doi: 10.1210/jc.2010-2784. Epub 2011 Mar 16.

  PMID: 21411557 BACKGROUND

• Brown JP, Roux C, Torring O, Ho PR, Beck Jensen JE, Gilchrist N, Recknor C, Austin M, Wang A, Grauer A, Wagman RB. Discontinuation of denosumab and associated fracture incidence: analysis from the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial. J Bone Miner Res. 2013 Apr;28(4):746-52. doi: 10.1002/jbmr.1808.

  PMID: 23109251 BACKGROUND

• Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C; FREEDOM Trial. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009 Aug 20;361(8):756-65. doi: 10.1056/NEJMoa0809493. Epub 2009 Aug 11.

  PMID: 19671655 BACKGROUND

• Eastell R, Christiansen C, Grauer A, Kutilek S, Libanati C, McClung MR, Reid IR, Resch H, Siris E, Uebelhart D, Wang A, Weryha G, Cummings SR. Effects of denosumab on bone turnover markers in postmenopausal osteoporosis. J Bone Miner Res. 2011 Mar;26(3):530-7. doi: 10.1002/jbmr.251.

  PMID: 20839290 BACKGROUND

• Freemantle N, Cooper C, Diez-Perez A, Gitlin M, Radcliffe H, Shepherd S, Roux C. Results of indirect and mixed treatment comparison of fracture efficacy for osteoporosis treatments: a meta-analysis. Osteoporos Int. 2013 Jan;24(1):209-17. doi: 10.1007/s00198-012-2068-9. Epub 2012 Jul 26.

  PMID: 22832638 BACKGROUND

• Genant HK, Libanati C, Engelke K, Zanchetta JR, Hoiseth A, Yuen CK, Stonkus S, Bolognese MA, Franek E, Fuerst T, Radcliffe HS, McClung MR. Improvements in hip trabecular, subcortical, and cortical density and mass in postmenopausal women with osteoporosis treated with denosumab. Bone. 2013 Oct;56(2):482-8. doi: 10.1016/j.bone.2013.07.011. Epub 2013 Jul 17.

  PMID: 23871852 BACKGROUND

• Hadji P, Bock O, Resch H, Kraenzlin M, Wang A, Steinle T, Eisen C. Reduction of fracture risk with denosumab among women with osteoporosis with or without need for treatment according to DVO 2009 guideline : A subgroup analysis of the FREEDOM trial. Osteologie. 2013;22(1):39-45.

  BACKGROUND

• Jamal SA, Ljunggren O, Stehman-Breen C, Cummings SR, McClung MR, Goemaere S, Ebeling PR, Franek E, Yang YC, Egbuna OI, Boonen S, Miller PD. Effects of denosumab on fracture and bone mineral density by level of kidney function. J Bone Miner Res. 2011 Aug;26(8):1829-35. doi: 10.1002/jbmr.403.

  PMID: 21491487 BACKGROUND

• Keaveny TM, McClung MR, Genant HK, Zanchetta JR, Kendler D, Brown JP, Goemaere S, Recknor C, Brandi ML, Eastell R, Kopperdahl DL, Engelke K, Fuerst T, Radcliffe HS, Libanati C. Femoral and vertebral strength improvements in postmenopausal women with osteoporosis treated with denosumab. J Bone Miner Res. 2014 Jan;29(1):158-65. doi: 10.1002/jbmr.2024.

  PMID: 23794225 BACKGROUND

• Mackey DC, Black DM, Bauer DC, McCloskey EV, Eastell R, Mesenbrink P, Thompson JR, Cummings SR. Effects of antiresorptive treatment on nonvertebral fracture outcomes. J Bone Miner Res. 2011 Oct;26(10):2411-8. doi: 10.1002/jbmr.446.

  PMID: 21710615 BACKGROUND

• McCloskey EV, Johansson H, Oden A, Austin M, Siris E, Wang A, Lewiecki EM, Lorenc R, Libanati C, Kanis JA. Denosumab reduces the risk of osteoporotic fractures in postmenopausal women, particularly in those with moderate to high fracture risk as assessed with FRAX. J Bone Miner Res. 2012 Jul;27(7):1480-6. doi: 10.1002/jbmr.1606.

  PMID: 22431426 BACKGROUND

• McClung MR, Boonen S, Torring O, Roux C, Rizzoli R, Bone HG, Benhamou CL, Lems WF, Minisola S, Halse J, Hoeck HC, Eastell R, Wang A, Siddhanti S, Cummings SR. Effect of denosumab treatment on the risk of fractures in subgroups of women with postmenopausal osteoporosis. J Bone Miner Res. 2012 Jan;27(1):211-8. doi: 10.1002/jbmr.536.

  PMID: 21976367 BACKGROUND

• McClung MR, Zanchetta JR, Hoiseth A, Kendler DL, Yuen CK, Brown JP, Stonkus S, Goemaere S, Recknor C, Woodson GC, Bolognese MA, Franek E, Brandi ML, Wang A, Libanati C. Denosumab densitometric changes assessed by quantitative computed tomography at the spine and hip in postmenopausal women with osteoporosis. J Clin Densitom. 2013 Apr-Jun;16(2):250-6. doi: 10.1016/j.jocd.2012.02.014. Epub 2012 May 8.

  PMID: 22572531 BACKGROUND

• Samelson EJ, Miller PD, Christiansen C, Daizadeh NS, Grazette L, Anthony MS, Egbuna O, Wang A, Siddhanti SR, Cheung AM, Franchimont N, Kiel DP. RANKL inhibition with denosumab does not influence 3-year progression of aortic calcification or incidence of adverse cardiovascular events in postmenopausal women with osteoporosis and high cardiovascular risk. J Bone Miner Res. 2014 Feb;29(2):450-7. doi: 10.1002/jbmr.2043.

  PMID: 23873632 BACKGROUND

• Silverman S, Viswanathan HN, Yang YC, Wang A, Boonen S, Ragi-Eis S, Fardellone P, Gilchrist N, Lips P, Nevitt M, Palacios Gil-Antunano S, Pavelka K, Revicki D, Simon J, Macarios D, Siris ES. Impact of clinical fractures on health-related quality of life is dependent on time of assessment since fracture: results from the FREEDOM trial. Osteoporos Int. 2012 Apr;23(4):1361-9. doi: 10.1007/s00198-011-1720-0. Epub 2011 Jul 19.

  PMID: 21769664 BACKGROUND

• Simon JA, Recknor C, Moffett AH Jr, Adachi JD, Franek E, Lewiecki EM, McClung MR, Mautalen CA, Ragi-Eis S, Nicholson GC, Muschitz C, Nuti R, Torring O, Wang A, Libanati C. Impact of denosumab on the peripheral skeleton of postmenopausal women with osteoporosis: bone density, mass, and strength of the radius, and wrist fracture. Menopause. 2013 Feb;20(2):130-7. doi: 10.1097/gme.0b013e318267f909.

  PMID: 23010883 BACKGROUND

• Strom O, Jonsson B, Kanis JA. Intervention thresholds for denosumab in the UK using a FRAX(R)-based cost-effectiveness analysis. Osteoporos Int. 2013 Apr;24(4):1491-502. doi: 10.1007/s00198-012-2115-6. Epub 2012 Dec 7.

  PMID: 23224141 BACKGROUND

• Watts NB, Roux C, Modlin JF, Brown JP, Daniels A, Jackson S, Smith S, Zack DJ, Zhou L, Grauer A, Ferrari S. Infections in postmenopausal women with osteoporosis treated with denosumab or placebo: coincidence or causal association? Osteoporos Int. 2012 Jan;23(1):327-37. doi: 10.1007/s00198-011-1755-2. Epub 2011 Sep 3.

  PMID: 21892677 BACKGROUND

• Hara T, Hijikata Y, Matsubara Y, Watanabe N. Pharmacological interventions versus placebo, no treatment or usual care for osteoporosis in people with chronic kidney disease stages 3-5D. Cochrane Database Syst Rev. 2021 Jul 7;7(7):CD013424. doi: 10.1002/14651858.CD013424.pub2.

  PMID: 34231877 DERIVED

• Broadwell A, Chines A, Ebeling PR, Franek E, Huang S, Smith S, Kendler D, Messina O, Miller PD. Denosumab Safety and Efficacy Among Participants in the FREEDOM Extension Study With Mild to Moderate Chronic Kidney Disease. J Clin Endocrinol Metab. 2021 Jan 23;106(2):397-409. doi: 10.1210/clinem/dgaa851.

  PMID: 33211870 DERIVED

• Ferrari S, Lewiecki EM, Butler PW, Kendler DL, Napoli N, Huang S, Crittenden DB, Pannacciulli N, Siris E, Binkley N. Favorable skeletal benefit/risk of long-term denosumab therapy: A virtual-twin analysis of fractures prevented relative to skeletal safety events observed. Bone. 2020 May;134:115287. doi: 10.1016/j.bone.2020.115287. Epub 2020 Feb 21.

  PMID: 32092479 DERIVED

• Ferrari S, Eastell R, Napoli N, Schwartz A, Hofbauer LC, Chines A, Wang A, Pannacciulli N, Cummings SR. Denosumab in postmenopausal women with osteoporosis and diabetes: Subgroup analysis of FREEDOM and FREEDOM extension. Bone. 2020 May;134:115268. doi: 10.1016/j.bone.2020.115268. Epub 2020 Feb 10.

  PMID: 32058020 DERIVED

• Ferrari S, Butler PW, Kendler DL, Miller PD, Roux C, Wang AT, Huang S, Wagman RB, Lewiecki EM. Further Nonvertebral Fracture Reduction Beyond 3 Years for Up to 10 Years of Denosumab Treatment. J Clin Endocrinol Metab. 2019 Aug 1;104(8):3450-3461. doi: 10.1210/jc.2019-00271.

  PMID: 31125092 DERIVED

• Watts NB, Grbic JT, Binkley N, Papapoulos S, Butler PW, Yin X, Tierney A, Wagman RB, McClung M. Invasive Oral Procedures and Events in Postmenopausal Women With Osteoporosis Treated With Denosumab for Up to 10 Years. J Clin Endocrinol Metab. 2019 Jun 1;104(6):2443-2452. doi: 10.1210/jc.2018-01965.

  PMID: 30759221 DERIVED

• Dempster DW, Brown JP, Fahrleitner-Pammer A, Kendler D, Rizzo S, Valter I, Wagman RB, Yin X, Yue SV, Boivin G. Effects of Long-Term Denosumab on Bone Histomorphometry and Mineralization in Women With Postmenopausal Osteoporosis. J Clin Endocrinol Metab. 2018 Jul 1;103(7):2498-2509. doi: 10.1210/jc.2017-02669.

  PMID: 29672714 DERIVED

• Napoli N, Pannacciulli N, Vittinghoff E, Crittenden D, Yun J, Wang A, Wagman R, Schwartz AV. Effect of denosumab on fasting glucose in women with diabetes or prediabetes from the FREEDOM trial. Diabetes Metab Res Rev. 2018 May;34(4):e2991. doi: 10.1002/dmrr.2991. Epub 2018 Apr 16.

  PMID: 29430796 DERIVED

• Cummings SR, Ferrari S, Eastell R, Gilchrist N, Jensen JB, McClung M, Roux C, Torring O, Valter I, Wang AT, Brown JP. Vertebral Fractures After Discontinuation of Denosumab: A Post Hoc Analysis of the Randomized Placebo-Controlled FREEDOM Trial and Its Extension. J Bone Miner Res. 2018 Feb;33(2):190-198. doi: 10.1002/jbmr.3337. Epub 2017 Nov 22.

  PMID: 29105841 DERIVED

• Bone HG, Wagman RB, Brandi ML, Brown JP, Chapurlat R, Cummings SR, Czerwinski E, Fahrleitner-Pammer A, Kendler DL, Lippuner K, Reginster JY, Roux C, Malouf J, Bradley MN, Daizadeh NS, Wang A, Dakin P, Pannacciulli N, Dempster DW, Papapoulos S. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. Lancet Diabetes Endocrinol. 2017 Jul;5(7):513-523. doi: 10.1016/S2213-8587(17)30138-9. Epub 2017 May 22.

  PMID: 28546097 DERIVED

• Zebaze R, Libanati C, McClung MR, Zanchetta JR, Kendler DL, Hoiseth A, Wang A, Ghasem-Zadeh A, Seeman E. Denosumab Reduces Cortical Porosity of the Proximal Femoral Shaft in Postmenopausal Women With Osteoporosis. J Bone Miner Res. 2016 Oct;31(10):1827-1834. doi: 10.1002/jbmr.2855. Epub 2016 May 19.

  PMID: 27082709 DERIVED

• Reid IR, Miller PD, Brown JP, Kendler DL, Fahrleitner-Pammer A, Valter I, Maasalu K, Bolognese MA, Woodson G, Bone H, Ding B, Wagman RB, San Martin J, Ominsky MS, Dempster DW; Denosumab Phase 3 Bone Histology Study Group. Effects of denosumab on bone histomorphometry: the FREEDOM and STAND studies. J Bone Miner Res. 2010 Oct;25(10):2256-65. doi: 10.1002/jbmr.149.

  PMID: 20533525 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Osteoporosis; Osteoporosis, Postmenopausal

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

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 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2004
• First Posted: August 16, 2004
• Study Start: August 1, 2004
• Primary Completion: June 17, 2008
• Study Completion: June 17, 2008
• Last Updated: November 8, 2022
• Results First Posted: January 10, 2014

Record last verified: 2022-11