Transition From Alendronate to Romosozumab (AMG 785)

Phase 1

Completed

Conditions: Osteoporosis

Interventions: Drug: Romosozumab

Registration Number: NCT01588509

Lead Sponsor: Amgen

Brief Summary: The purpose of this study is to estimate the percent change from baseline in lumbar spine bone mineral density (BMD) following multiple-dose administrations of romosozumab in postmenopausal women with low BMD previously treated with alendronate.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 60

Inclusion Criteria

Postmenopausal women, defined as no vaginal bleeding or spotting for ≥ 12 months
Low bone mineral density at screening [defined by a bone mineral density (BMD) T-score ≤ -2.0 and ≥ -4.0 at the lumbar spine (L1 to L4; or BMD T-score of evaluable vertebrae), total hip, or femoral neck]
Currently taking alendronate (70 mg weekly or equivalent) exclusively for ≥ 1 year with verbal agreement that the subject has taken ≥ 80% of their doses with good tolerance

Exclusion Criteria

History of vertebral fracture, or fragility fracture of the wrist, humerus, hip or pelvis after age 50; or recent bone fracture within 6 months prior to screening
History of metabolic or bone disease such as Paget's disease, rheumatoid arthritis, osteomalacia, osteogenesis imperfecta, osteopetrosis, ankylosing spondylitis, Cushing's disease, hyperprolactinemia, and malabsorption syndrome
Vitamin D deficiency (defined as 25-OH-VitD levels < 20 ng/mL)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Romosozumab 140 mg	Romosozumab	Participants received romosozumab 140 mg administered subcutaneously once a month for 3 months.
Romosozumab 210 mg	Romosozumab	Participants received romosozumab 210 mg administered subcutaneously once a month for 3 months.

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Bone Mineral Density (BMD) at the Lumbar Spine	Baseline and day 85	Bone mineral density was assessed by dual energy X-ray absorptiometry (DXA) scans of the lumbar spine (L1-L4) and analyzed by a central imaging lab.

Secondary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Serum Type-1 Aminoterminal Propeptide (P1NP)	Baseline and days 4, 15, 29, 43, 57, 71, and 85
Percent Change From Baseline in Bone Mineral Density (BMD) at the Femoral Neck	Baseline and day 85	Bone mineral density was assessed by dual energy X-ray absorptiometry (DXA) scans and analyzed by a central imaging lab.
Number of Participants With Adverse Events	From first dose of study drug up to day 85	An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participant. Laboratory value changes that required treatment or adjustment in current therapy were considered adverse events. A treatment-related adverse event (TRAE) was an adverse event assessed by the investigator as possibly related to the investigational product, indicated by a "yes" response to the question: Is there a reasonable possibility that the event may have been caused by the investigational product? A serious adverse event was defined as an adverse event that met at least 1 of the following serious criteria: * fatal, * life-threatening, * required in-patient hospitalization or prolongation of existing hospitalization, * resulted in persistent or significant disability/incapacity, * congenital anomaly/birth defect, and/or * other medically important serious event.
Mean Serum Concentration of Romosozumab	Days 4, 15, 29, 43, 57, 71 and 85
Percent Change From Baseline in Bone Mineral Density (BMD) at the Total Hip	Baseline and day 85	Bone mineral density was assessed by dual energy X-ray absorptiometry (DXA) scans and analyzed by a central imaging lab.
Percent Change From Baseline in Serum C-telopeptide (sCTX)	Baseline and days 4, 15, 29, 43, 57, 71, and 85
Number of Participants Who Developed Anti-romosozumab Antibodies	Baseline and days 29, 57, and 85	Two validated assays were used to detect the presence of anti-romosozumab antibodies. An electrochemiluminescent bridging immunoassay was used to detect binding antibodies (screening assay) and confirm antibodies (confirmatory assay) capable of binding romosozumab. Samples testing positive in the immunoassay were further tested in a competitive binding bioassay for neutralizing activity against romosozumab. If a sample was positive for binding antibodies and demonstrated neutralizing activity, the participant was defined as positive for neutralizing antibodies. Participants who developed anti-romosozumab antibodies were those with a negative result at baseline and a positive result at any time postbaseline.