Table 1

Clinical trials investigating the effects of denosumab

Study name or title on http://www.clinicaltrials.gov
Phase
n
Primary end-point

Osteoporosis



     A single dose, placebo-controlled study of AMG 162, a fully human mAb to RANKL, in postmenopausal women [6]
phase 1
49
Pharmacokinetics and pharmacodynamics
     A randomized, double-blind, placebo-controlled, multidose phase 2 study to determine the efficacy, safety, and tolerability of AMG 162 in the treatment of postmenopausal women with low BMD [14]
phase 2
412
BMD
     A randomized, double-blind, placebo-controlled, dose-response study of AMG 162 (denosumab) in Japanese postmenopausal osteoporotic women
phase 2
-
BMD
     A multicenter, randomized, placebo-controlled, pilot microCT study to estimate the effect of treatment with denosumab (AMG 162) and alendronate sodium in postmenopausal women with low BMD
phase 2
240
Distal radius measurements as determined by Xtreme CT
     A study to evaluate AMG 162 in the treatment of postmenopausal osteoporosis
phase 3
7,800
Fracture
     A randomized, double-blind study to compare the efficacy of treatment with denosumab with that of alendronate sodium in postmenopausal women with low BMD
phase 3
1,100
BMD
     A randomized, double-blind study to evaluate safety and efficacy of transitioning therapy from alendronate to denosumab (AMG 162) in postmenopausal women with low BMD
phase 3
500
BMD
     A randomized, double-blind study to evaluate AMG 162 in the prevention of postmenopausal osteoporosis
phase 3
300
BMD
     An open-label, single arm extension study to evaluate the long-term safety of denosumab administration in postmenopausal women with low BMD
Phase 3
-
Safety
Bone metastases/multiple myeloma



     A study of the biological RANKL inhibitor denosumab in subjects with multiple myeloma or bone metastases from breast cancer [13]
phase 1
54
Pharmacokinetics and pharmacodynamics
     Randomized, active-controlled study of denosumab (AMG162) in breast cancer patients with bone metastasis previously treated with intravenous bisphosphonates [16]
phase 2
255
Urine NTX
     A randomized trial of denosumab (AMG 162) versus intravenous bisphosphonates in cancer patients with bone metastases on established IV BP and evidence of elevated bone resorption [15]
phase 2
135
Urine NTX
     An open-label, multicenter, phase 2 trial of denosumab in the treatment of relapsed or plateau-phase multiple myeloma
phase 2
100
Complete response/partial response
     An open-label, multicenter, phase 2 safety and efficacy study of denosumab (AMG 162) in subjects with recurrent or unresectable giant cell tumor (GCT) of bone
phase 2
25
Response rate based on imaging or tissue samples
     A randomized, double-blind multicenter study of denosumab compared with zoledronic acid in the treatment of bone metastases in men with hormone-refractory prostate cancer
phase 3
1,700
Skeletal related events
     A randomized, double-blind, multicenter study of denosumab compared with zoledronic acid in the treatment of bone metastases in subjects with advanced breast cancer
phase 3
1,400
Skeletal related events
     Double-blind study of denosumab compared with zoledronic acid in the treatment of bone metastases in subjects with advanced cancer (excluding breast and prostate cancer) or multiple myeloma
phase 3
1,700
Skeletal related events
     A randomized, double-blind, placebo-controlled, multicenter phase 3 study of denosumab on prolonging bone metastasis-free survival in men with hormone refractory prostate cancer
phase 3
1,400
Time to first occurence of bone metastasis or death from any cause
Treatment-induced bone loss



     A randomized, double-blind, placebo-controlled study to evaluate AMG 162 in the treatment of bone loss in patients undergoing androgen deprivation therapy for nonmetastatic prostate cancer
phase 3
1,400
BMD
     A randomized, double-blind, placebo-controlled study to evaluate AMG 162 in the treatment of bone loss in patients undergoing aromatase inhibitor therapy for nonmetastatic breast cancer
phase 3
208
BMD
Rheumatoid arthritis



     A randomized, double-blind, placebo-controlled, multidose phase 2 study to determine the efficacy, safety, and tolerability of AMG 162 in the treatment of rheumatoid arthritis [17]
phase 2
227
Bone erosions

CT, computed tomography; mAb, monoclonal antibody; NTX, N-telopeptide; RANKL, receptor activator of nuclear factor-κB ligand.

Schwarz and Ritchlin Arthritis Research & Therapy 2007 9(Suppl 1):S7   doi:10.1186/ar2171