Table 1.

Important Phase I, Phase II, and Phase III studies of romosozumab

Study ID	Study name/study phase	Study participants	Dosages	Primary endpoint	Conclusion
NCT01059435	A first-in-human study evaluating AMG 785 in healthy men and postmenopausal women Phase I study	72 healthy males and females, aged 45–59 years Patients randomized to receive romosozumab or placebo in a 3:1 ratio	One dose of romosozumab administered subcutaneously or intravenously: subcutaneous dosing – 0.1, 0.3, 1, 3, 5, or 10 mg/kg and intravenous dosing – 1 or 5 mg/kg	The number of subjects reporting treatment-emergent adverse events The number of subjects experiencing clinically significant changes in vital signs, physical examinations, safety laboratory tests, or electrocardiograms The number of subjects who develop antibodies to romosozumab	Romosozumab well tolerated No deaths or study discontinuations One treatment-related serious adverse event of nonspecific hepatitis that resolved after cessation of the drug Six subjects receiving higher doses of romosozumab developed romosozumab antibodies Neutralizing antibodies in two subjects No discernible effect of neutralizing antibodies on pharmacokinetics or pharmacodynamics
NCT01825785	A multiple dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AMG 785 Phase I study	48 healthy males and postmenopausal females, aged 45–80 years with low bone mass Patients randomized to receive romosozumab or placebo in a 3:1 ratio	Romosozumab administered subcutaneously Postmenopausal women: – 6 doses of 1 or 2 mg/kg (every 2 weeks) – 3 doses of 2 or 3 mg/kg (every 4 weeks) Healthy men: – 6 doses of 1 mg/kg (every 2 weeks) – 3 doses of 3 mg/kg (every 4 weeks)	The number of subjects reporting treatment-emergent adverse events The number of subjects experiencing clinically significant changes in vital signs, physical examination, safety laboratory tests, or electrocardiograms The number of subjects who develop antibodies to romosozumab	Romosozumab well tolerated No deaths Two study discontinuations: – One subject discontinued due to the development of pruritus related to treatment – One subject discontinued due to unclear reasons Adverse event rates balanced between groups No significant safety findings 13 subjects developed romosozumab antibodies Neutralizing antibodies in two subjects No discernable effects of neutralizing antibodies on pharmacokinetics or pharmacodynamics
NCT00896532	Phase II study of AMG 785 in postmenopausal women with low BMD Phase II study	419 postmenopausal women, aged 55–85 years with low BMD Patients randomized to receive romosozumab, placebo, or an open-label active comparator (oral alendronate 70 mg weekly or subcutaneous teriparatide 20 μg daily)	Subcutaneous romosozumab for 12 months at various doses – 70, 140, or 210 mg (monthly) – 140 and 210 mg (every 3 months)	Percentage change from baseline to month 12 in BMD at the lumbar spine for the individual romosozumab groups and pooled placebo arm	There were significant increases in lumbar spine BMD at month 12 with all doses of romosozumab Of all doses studied, romosozumab 210 mg monthly dosing had the largest BMD gain of 11.3% The lumbar spine bone density gain with monthly romosozumab 210 mg was larger than placebo (0.1% BMD decrease), open label active comparators-alendronate (4.1% BMD increase), and teriparatide (7.1% BMD increase)
NCT01575834	Registrational study with AMG 785 to treat postmenopausal osteoporosis Phase III study	7,180 postmenopausal women, with osteoporosis (T-score of −2.5 to −3.5 at the total hip or femoral neck) Patients randomized to receive romosozumab or placebo for 12 months, followed by denosumab for 12 months in both groups	Monthly subcutaneous romosozumab 210 mg for 12 months	Incidence of vertebral fracture at 12 and 24 months	Decreased risk of vertebral fracture by 73% at 12 months and 75% at 24 months in the romosozumab group as compared to the placebo group

Abbreviation: BMD, bone mineral density.