A Study to Evaluate the Effect of Romosozumab (AMG 785) on Bone Quality of the Forearm in Postmenopausal Women With Low Bone Mass

A Randomized, Double-blind, Placebo-controlled, Multiple Dose Study to Evaluate the Effect of AMG 785 on Parameters of Bone Quality of the Forearm Using pQCT in Postmenopausal Women With Low Bone Mineral Density

The purpose of this study is to evaluate the effect of romosozumab on parameters of bone quality of the forearm using peripheral quantitative computed tomography (pQCT) following multiple subcutaneous dose administrations of romosozumab in postmenopausal women with low bone mass.

Inclusion Criteria:

• Healthy females between 55 to 80 years of age

• Postmenopausal females (based on medical history) defined as 12 continuous months of spontaneous amenorrhea

  • Women 60 years of age and older will be considered postmenopausal
  • Women 55-59 must have a serum follicle-stimulating hormone result > 40 mIU/mL and serum estradiol ≤ 20 pg/mL

• Low bone mineral density (BMD), defined as a BMD T-score between -1.0 and -2.5 at the lumbar spine (L1-L4) and/or femoral neck

• Weight ≤ 98 kg (216 lb) and/or height ≤ 196 cm (77 in)

• 25-hydroxyvitamin D ≥ 20 ng/mL at screening

• Willing and able to take ≥ 500 mg calcium and ≥ 400 IU (but ≤ 1,000 IU) vitamin D daily

Exclusion Criteria:

• Osteoporosis, defined as a BMD T-score ≤ -2.5 at the lumbar spine or femoral neck

• History of vertebral fracture, or fragility fracture of the wrist, humerus, hip or pelvis

• Diagnosed with any condition that will affect bone metabolism

• Subjects with fewer than 2 evaluable vertebrae; metal in forearms bilaterally that would not allow for at least one evaluable forearm

• Administration of the following medications within 6 months before study drug administration. This includes all routes of administration, for example intranasal and topical skin patches, unless otherwise noted:

  • Hormone replacement therapy [(eg, estrogen, estrogen-like compounds such as raloxifene). Infrequent use of estrogen vaginal creams (< 3 times per week) is allowed.]
  • Calcitonin
  • Parathyroid hormone (or any derivative)
  • Glucocorticosteroids (inhaled or topical corticosteroids administered more than 2 weeks before the enrollment date are allowed)
  • Anabolic steroids
  • Calcitriol, and available analogues

• Administration of daily, weekly, or monthly bisphosphonates (BP) unless meeting the following criteria:

  • < 2 weeks of BP use requires a 2-month washout period
  • 2 weeks to 3 months of BP use requires a 9-month washout period
  • 3 to 6 months of BP use requires a 1-year washout period
  • > 6 months of BP use requires a 3-year washout period;

• Greatly differing levels of physical activity or constant levels of intense physical exercise during the 6 months before study drug administration

• Known sensitivity to mammalian-derived drug preparations

• Known to be hepatitis B surface antigen, hepatitis C virus or human Immunodeficiency virus (HIV) positive or a known diagnosis of acquired immunodeficiency syndrome (AIDS)

• Any organic or psychiatric disorder, which, in the opinion of the investigator, poses a risk to subject safety and may prevent the subject from completing the study or interfere with the interpretation of the study results

• Unavailable for follow-up assessment or any concerns for subject's compliance with the protocol procedures

• Any other condition that might reduce the chance of obtaining data required by the protocol or that might compromise the ability to give truly informed consent

• History or evidence of a clinically significant disorder, condition or disease that, in the opinion of the Investigator or Amgen physician would pose a risk to subject safety or interfere with the study evaluation, procedures or completion

• Clinically significant abnormality during the screening physical examination, electrocardiogram (ECG) or laboratory evaluation

• Participation in another clinical study within 4 weeks of screening or within 5 times the half-life of the investigational agent in the other clinical study, if known

• Has donated or lost 400 mL or more of blood or plasma within 8 weeks of study drug administration

• Previous AMG 785 exposure