Romosozumab (AMG 785) in Postmenopausal Women With Low Bone Mineral Density
Condition: Low Bone Mineral Density; Postmenopausal Osteoporosis
MeSH terms: Osteoporosis; Osteoporosis, Postmenopausal; Bone Diseases, Metabolic
Intervention: Placebo to Romosozumab; Alendronate; Teriparatide; Romosozumab; Denosumab; Placebo to Denosumab; Zoledronic acid
Intervention description: Administered by subcutaneous injection QM or Q3M.; Administered orally once a week; Teriparatide 20 μg administered by subcutaneous injection once a day; Administered by subcutaneous injection; Denosumab 60 mg administered by subcutaneous injection Q6M; Administered by subcutaneous injection Q6M; Zoledronic acid 5 mg administered intravenously
Intervention MeSH terms: Zoledronic Acid; Denosumab; Alendronate; Teriparatide; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 419.0
Sex: Female
Minimum age: 55 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      The primary objective was to determine the effect of treatment with romosozumab versus
      placebo at month 12 on the percent change from baseline in bone mineral density (BMD) at the
      lumbar spine in postmenopausal women with low bone density.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ambulatory, postmenopausal women, aged ≥ 55 to ≤ 85

          -  Low BMD measured by dual energy X-ray absorptiometry (DXA) and assessed by the central
             imaging vendor (equivalent to T-scores between -2.0 and -3.5)

        Exclusion Criteria:

          -  History of vertebral fracture, or fragility fracture of the wrist, humerus, hip or
             pelvis after age 50

          -  Untreated hyper- or hypothyroidism

          -  Current hyper- or hypoparathyroidism, hypo- or hypercalcemia

          -  Elevated transaminases

          -  Significantly impaired renal function

          -  Positive for: human immunodeficiency virus (HIV), hepatitis-C or hepatitis-B surface
             antigen

          -  Malignancy

          -  History of solid organ or bone marrow transplants

          -  Use of agents affecting bone metabolism

          -  Contraindicated or intolerant of alendronate therapy

          -  Contraindicated or intolerant of teriparatide therapy

        Inclusion Criteria for the 12 month extension phase (Month 24 to 36):

        - Normocalcemia at or after the Month 21 visit but before the Month 24 study visit

        Exclusion Criteria for the 12 month extension phase (Month 24 to 36)

          -  Incidence of a clinical vertebral fracture or fragility fracture of the wrist,
             humerus, hip or pelvis during the initial 24 month treatment phase of the study

          -  A BMD loss of ≥ 7.0% from baseline at any time up to the Month 18 visit of the initial
             24-month treatment phase

          -  Malignancy

          -  History of osteonecrosis of the jaw

          -  Use of proscribed medication during the initial 24 month treatment phase

          -  Contraindicated or intolerant of denosumab therapy

        Inclusion Criteria for the 12 month re-treatment phase (Month 36 to 48)

          -  Albumin adjusted serum calcium of the most recent blood draw at or after the Month 30
             visit but before the Month 36 study visit. Calcium repletion is permitted and central
             laboratory analysis of albumin adjusted serum calcium may be repeated before the Month
             36 study visit

          -  Participation in Group A or B during initial 24 month treatment phase

          -  Subject has reached M36 of the study

          -  Appropriate written informed consent must be obtained

        Exclusion Criteria for the 12 month re-treatment phase (Month 36 to 48)

          -  New malignancy

          -  Use of proscribed medication during the 12 month extension phase

        Inclusion Criteria for the 24 month follow-on phase (Month 48 to 72) General inclusion
        criteria for participation

          -  Subject has reached month 48 of the study

          -  Appropriate written informed consent must be obtained Inclusion criteria for
             assignment to the no intervention group

          -  During the 24 month AMG 785 treatment phase, subject was assigned to any AMG 785
             treatment group

          -  During the 12 month denosumab extension phase, subject was assigned to the denosumab
             treatment group Exclusion for the 24 month follow-on phase (Month 48 to 72)

          -  New malignancy

          -  Use of proscribed meds during the 12 month re-treatment phase

          -  Partial informed consent withdrawal and discontinuation of investigational product at
             any time up to month 48 visit

          -  Incidence of a clinical vertebral fracture or fragility fracture of the wrist,
             humerus, hip or pelvis during the initial 24 month treatment phase of the study

          -  BMD T-score of ≤ -2.5 at the lumbar spine, total hip, or femoral neck based on local
             read of the DXA scans at month 48

          -  Intolerance to zoledronic acid