A Study to Evaluate Denosumab in the Treatment of Postmenopausal Osteoporosis

Osteoporosis Clinical Trial

Official title:

A Study to Evaluate Denosumab in the Treatment of Postmenopausal Osteoporosis FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis Every 6 Months)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00089791
• Other study ID #: 20030216
• Status: Completed
• Phase: Phase 3
• Start date: August 1, 2004
• Est. completion date: June 17, 2008

Study information

• Verified date: November 2022
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7808
• Est. completion date: June 17, 2008
• Est. primary completion date: June 17, 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 60 Years to 90 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Osteoporosis
• Osteoporosis, Postmenopausal

Intervention

Drug:
• placebo
Placebo administered by subcutaneous injection
• Denosumab
Denosumab 60 mg administered by subcutaneous injection

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

References & Publications (21)

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, Möller 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. — View Citation

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. — View Citation

Bolognese MA, Teglbjærg CS, Zanchetta JR, Lippuner K, McClung MR, Brandi ML, Høiseth 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. — View Citation

Boonen S, Adachi JD, Man Z, Cummings SR, Lippuner K, Törring 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. — View Citation

Brown JP, Roux C, Törring 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. — View Citation

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. Erratum in: N Engl J Med. 2009 Nov 5;361(19):1914. — View Citation

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. — View Citation

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. — View Citation

Genant HK, Libanati C, Engelke K, Zanchetta JR, Høiseth 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. — View Citation

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.

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum in: J Bone Miner Res. 2017 Nov;32(11):2319. — View Citation

McClung MR, Boonen S, Törring 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. — View Citation

McClung MR, Zanchetta JR, Høiseth 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. — View Citation

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. — View Citation

Silverman S, Viswanathan HN, Yang YC, Wang A, Boonen S, Ragi-Eis S, Fardellone P, Gilchrist N, Lips P, Nevitt M, Palacios Gil-Antuñano 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. — View Citation

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, Törring 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. — View Citation

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

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. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of Participants With Nonvertebral Fractures	Nonvertebral fractures (osteoporotic) were those occurring on study excluding those of the vertebrae (cervical, thoracic, and lumbar), skull, facial, mandible, metacarpus, finger phalanges, and toe phalanges. Fractures associated with high trauma severity (fractures that were the result of a fall from higher than the height of a stool, chair, first rung on a ladder or equivalent (> 20 inches) or was the result of severe trauma other than a fall) and pathologic fractures were excluded from this category. Nonvertebral fractures were required to be confirmed either by radiographs or other diagnostic images such as computerized tomography (CT) or magnetic resonance imaging (MRI), or by documentation in a radiology report, surgical report, or discharge summary.	36 months
Secondary	Number of Participants With a Hip Fracture	Hip fractures are a subset of nonvertebral fractures including femur neck, femur intertrochanter, and femur subtrochanter.	36 months

External Links

•   AmgenTrials clinical trials website