Table 1: Chronological listing of clinical trials of sclerostin neutralising antibodies.

Clinical trial identifierPhaseStudy nameNumber of participants and populationTreatment interventionPrimary endpointStudy completion date (actual/estimate)

NCT01059435IA First-in-Human Study Evaluating AMG 785 (Romosozumab) in Healthy Men and Postmenopausal Women74
healthy males; postmenopausal females, ages 45–59 years
Postmenopausal women: one dose of romosozumab: 0.1, 0.3, 1, 3, 5, or 10 mg/kg SC or 1 or 5 mg/kg IV or placebo SC or IV
Men: one dose of romosozumab: 1 or 5 mg/kg SC or IV or placebo
Number of subjects (%) experiencing clinically significant changes in vital signs, physical exam, laboratory tests, and ECGs; developing anti-AMG 785 antibodies; reporting treatment-emergent adverse events up to 85 days after drug administrationAugust 2008

NCT01825785IA Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 78548
healthy males and postmenopausal females (osteopenia), ages 45–80 years
1 mg/kg SC every 2 weeks × 6 doses; romosozumab or placebo
3 mg/kg every 4 weeks × 3 doses; romosozumab or placebo
2 mg/kg every 2 weeks × 6 doses; romosozumab or placebo 2 mg/kg every 4 weeks × 3 doses
Number of subjects (%) with clinically significant changes in vital signs, physical exam, laboratory tests, and ECGs; developing anti-AMG 785 antibodies; reporting treatment-emergent adverse events up to 169 days after initial drug administrationJuly 2009

NCT00902356IA First-in-Human Study Evaluating AMG 167 in Healthy Men and Postmenopausal Women69
healthy males and postmenopausal females (osteopenia) ages 45–65 years
Postmenopausal women: one dose AMG 167 or placebo 21 mg, 70, 210, 350, or 700 mg SC or 70 mg or 350 mg IV
Men: 70 mg or 350 mg SC or IV
Number of subjects (%) experiencing clinically significant changes in safety laboratory tests, physical examinations, vital signs, or ECGs; developing anti-AMG 167 antibodies; reporting treatment-emergent adverse events up to 85 days after drug administrationNovember 2009

NCT01742091IA Multiple-Dose Study of LY2541546 (Eli Lilly) in Healthy Postmenopausal Women59
healthy postmenopausal females, ages 45–80 years
180 mg LY2541546 SC Q4W for 8 weeks or placebo at weeks 2 and 6
270 mg LY2541546 SC Q2W or Q4W for 8 weeks or placebo at weeks 2 and 6
540 mg IV Q4W for 8 weeks or placebo IV at weeks 2 and 6
750 mg LY2541546 IV Q2W for 8 weeks
Placebo comparator IV or SC Q2W for 8 weeks
Number of subjects with 1+ SAE up to 141 days after drug administrationMarch 2010

NCT01742078IA Study of LY2541546 in Healthy Postmenopausal Women60
healthy postmenopausal females, ages 45–70 years
Single dose of 7.5 mg; 25 mg; 75 mg; 225 mg; 750 mg LY2541546 IV; single dose of 150 mg LY2541546 SC; single dose of placebo administered IV or SC; single dose of 225 mg or 750 mg LY2541546 IV, OLNumber of subjects with 1+ SAE up to 85 days after drug administrationJune 2010

NCT01101061IA Single-Dose Study Evaluating AMG 785 in Healthy Postmenopausal Japanese Women31
Japanese postmenopausal females, ages 45–70 years
Postmenopausal Japanese women: 1 mg/kg, 3 mg/kg, or 5 mg/kg AMG 785 or placebo
Postmenopausal non-Japanese women: 3 mg/kg AMG 785 or placebo
Number of subjects (%) experiencing clinically significant changes in vital signs, physical exam, laboratory tests, and ECGs; developing anti-AMG 785 antibodies; reporting treatment-emergent adverse events up to 85 days after drug administrationNovember 2010

NCT00950950IA Study to Evaluate the Effect of AMG 785 on Bone Quality of the Forearm in Postmenopausal Women With Low Bone Mass24
healthy and postmenopausal females (osteopenia), ages 55–80 years
3 mg/kg AMG 785 or placebo SC of every 4 weeks for 3 monthsPolar cross-sectional moment of inertia at the distal radius assessed by pQCT up to 169 days after drug administrationDecember 2010

NCT00896532IIPhase 2 Study of AMG 785 in Postmenopausal Women With Low Bone Mineral Density419
postmenopausal women with low BMD (-score between −2.0 and −3.5), ages 55–85 years
() Romosozumab 70 mg, 140 mg, or 210 mg or placebo QM
() Teriparatide 20 mcg QD
() Romosozumab 140 mg or 210 mg or placebo every Q3M
() Alendronate 70 mg QW
() Denosumab 60 mg or placebo Q6M
() Zoledronic acid 5 mg IV annually
% change from baseline at month 12 in bone mineral density at the lumbar spine for the individual AMG 785 groups and pooled placebo armsApril 2016

NCT01101048IAscending-Multiple-Dose Study Evaluating AMG 167 in Healthy Men and Postmenopausal Women With Low Bone Mineral Density74
healthy men and postmenopausal women (low BMD), ages 45–75
Postmenopausal women: AMG 167 or placebo in one of 3 fixed doses SC
Healthy men: AMG 167 or placebo in one of 2 fixed doses SC (doses not specified)
Number of subjects (%) experiencing clinically significant changes in vital signs, physical exam, laboratory tests, and ECGs; developing anti-AMG 785 antibodies; reporting treatment-emergent adverse events up to 336 days after drug administrationFebruary 2012

NCT00907296IIA Study of AMG 785 in Tibial Diaphyseal Fractures Status Post Intramedullary Nailing402
skeletally mature adults with a unilateral closed or Gustilo type I or II open tibial fracture and fracture fixation with intramedullary nailing, ages 18–85 years
Two, three, or four doses of AMG 785 70 mg, 140 mg, or 210 mg or four doses of placeboTime to radiographic healing for AMG 785 versus placebo groups over 24 weeksSeptember 2012

NCT01406977IIDose Escalation Study to Evaluate the Safety and Tolerability of Multiple Infusions of BPS804 (Novartis) in Adults with Hypophosphatasia9
healthy male and female subjects, ages 18–70 years
Dose escalation (doses not specified)Number (%) of subjects experiencing adverse events or SAE; change from baseline in primary serological bone biomarkers up to 141 days after drug administrationSeptember 2012

NCT01417091IISafety, Pharmacokinetics and Pharmacodynamics of BPS804 in Osteogenesis Imperfecta10
male and females with osteogenesis imperfecta, ages 18–75 years
Dose escalation (doses not specified) versus placeboSafety and tolerability; pharmacodynamic effect by means of biomarkers (days 1 and 43); change in -score from baseline to day 141December 2012

NCT01081678IIStudy to Assess Fracture Healing with Sclerostin Antibody332
males and females unilateral low energy intertrochanteric or femoral neck fracture as the primary injury, ages 55–95 years
Four doses of 70 mg, 140 mg, or 210 mg AMG 785 or placebo SC over 52 weeksFunctional healing as measured by the mean value for the timed-up-and-go test over weeks 6 to 20January 2013

NCT01588509ITransition from Alendronate to AMG 78560
postmenopausal women (low BMB), ages 55–85 years
Three doses of AMG 785 dose 1 or dose 2 (not specified)Change in lumbar spine BMD from baseline at day 85January 2013

NCT01144377IIA Study of LY2541546 in Women with Low Bone Mineral Density153
postmenopausal women (low BMB), ages 45–85 years
LY2541546 SC every 4 weeks with placebo given every alternate 2 weeks (patient will receive an injection every 2 weeks) for 52 weeks
180 mg or 270 mg LY2541546 SC or placebo given every 2 weeks for 52 weeks
LY2541546 SC every 12 weeks or placebo every 2 weeks when LY2541546 is not administered for 52 weeks
Change from baseline to 52-week endpoint in lumbar spine BMDFebruary 2013

NCT01406548IISafety and Efficacy of Multiple-Dosing Regimens of BPS804 in Postmenopausal Women with Low Bone Mineral Density44
postmenopausal women (low BMD), ages 45–85 years
BPS804 or placebo at dosing frequency 1, 2, or 3 (not specified)Change from baseline in BMD in lumbar spine to month 9 in bone mineral density at the lumbar spine for the individual BPS804 groups and pooled placebo arms after 9 months; number (%) of subjects experiencing adverse events or SAEOctober 2013

NCT01833754IStudy of Romosozumab (AMG 785) Administered to Healthy Subjects and Subjects with Stage 4 Renal Impairment or Stage 5 Renal Impairment Requiring Haemodialysis24
males and females, age ≥ 50 years (healthy, stage 4 renal impairment; end-stage renal disease)
Single-dose romosozumab SC (not specified) Incidence of treatment-emergent adverse events; results of safety laboratory tests, vital sign measurements or ECG measurements; development of anti-romosozumab antibodiesApril 2014

NCT02109042IA Study of Blosozumab (LY2541546) in Postmenopausal Female Participants40
postmenopausal females >60 years
Blosozumab SC QW SC for 6 weeksPharmacokinetics (max concentration of blosozumab; area under the concentration curve)July 2014

NCT02016716IIIA Randomized Phase 3 Study to Evaluate 2 Different Formulations of Romosozumab in Postmenopausal Women With Osteoporosis294
postmenopausal women with osteoporosis and high fracture risk, ages 55–90 years
Romosozumab formulation A or B or placebo (dose, frequency not specified)% change from baseline in DXA BMD in the lumbar spine 6 months after drug administration December 2014

NCT01992159IIStudy with AMG 785 to Treat Japanese Women with Postmenopausal Osteoporosis252
postmenopausal Japanese women with osteoporosis, ages 55–85 years
Romosozumab (three treatment arms, doses unknown) or placebo SC for 12 months (frequency not specified)% changes from baseline in lumbar spine BMD at 12 monthsJanuary 2015

NCT01796301IIIAn Open-Label Study to Evaluate the Effect of Treatment with AMG 785 or Teriparatide in Postmenopausal Women (STRUCTURE)436
postmenopausal females, BMD -score ≤ −2.50, ages 55–90 years
Romosozumab or teriparatide SC for 12 months% change from baseline in DXA BMD at the total hip through month 12January 2015

NCT02186171IIIA Double-blind Study to Compare the Safety and Efficacy of Romosozumab (AMG 785) versus Placebo in Men with Osteoporosis (BRIDGE)245
males, BMD -score ≤ 2.50 at the spine/hip, -score ≤ 1.50 at spine/hip, and a history of fragility nonvertebral/vertebral fracture
Monthly SC injection of romosozumab or placebo for 12 months% change from baseline in DXA BMD in lumbar spine at month 12December 2016

NCT01575834IIIRegistrational Study with AMG 785 to Treat Postmenopausal Osteoporosis (FRAME)7180
osteoporotic postmenopausal females, ages 55–90 years
Romosozumab SC or placebo for 12 months, followed by SC OL denosumab for 24 monthsIncidence of vertebral fracture at 12 and 24 monthsFebruary 2017

NCT01631214IIIStudy to Determine the Efficacy and Safety of Romosozumab in the Treatment of Postmenopausal Women with Osteoporosis4094
postmenopausal women with osteoporosis at high risk for fracture: hip BMD -score ≤ −2.5 SD and a vertebral fracture or hip BMD -score ≤ −2.0 SD and a recent hip fracture or two vertebral fractures, ages 55–90 years
Romosozumab SC injections and placebo alendronate (oral) for 12 months followed by OL alendronate (oral) for at least another 12 months (until end of study)
Oral alendronate and placebo AMG 785 subcutaneous injections for 12 months, followed by open-label alendronate (oral) for at least another 12 months (until end of study)
Incidence of clinical fracture or new vertebral fracture at 24 months after drug administrationMay 2017

BMD: bone mineral density; ECG: electrocardiogram; IV: intravenously; OL: open label; SAE: serious adverse events; SC: subcutaneously; QW: weekly; Q2W: once every 2 weeks; Q4W: once every four weeks; QD: daily; QM: every month.