Extension Study to Evaluate the Long Term Safety and Efficacy of Denosumab in the Treatment of Osteoporosis

Amgen4,550 enrolled

Overview

The primary objective was to describe the safety and tolerability of up to 10 years or 7 years denosumab administration as measured by adverse event monitoring, immunogenicity and safety laboratory parameters in participants who previously received denosumab or placebo, respectively.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

4,550

Conditions

Osteopenia Osteoporosis

Interventions

DenosumabBIOLOGICAL

Administered by subcutaneous injection once every 6 months.

Eligibility

Sex: FEMALEMin age: 60 YearsMax age: 94 Years

Medical Language ↔ Plain English

Postmenopausal women who have attended the 20030216 (NCT00089791) study month 36 visit will be eligible to participate if they meet the inclusion and exclusion criteria given below. Inclusion Criteria * Subjects must sign the informed consent before any study specific procedures are performed and agree to receive denosumab 60 mg subcutaneous injection every 6 months * Subjects must not have discontinued investigational product during the 20030216 study and must have attended the 20030216 study month 36 visit * Subjects must be re-consented prior to (or at) the 24 month visit for participation beyond month 24. Exclusion Criteria * Permanently non-ambulatory subjects (use of an assistive device eg, cane, walker, etc. is permitted) * Missed 2 or more investigational product doses during the 20030216 study * Any disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or comply with study procedures * Developed sensitivity to mammalian cell derived drug products during the 20030216 study * Unable to tolerate calcium supplementation during the last 6 months of participation in the 20030216 study (between the month 30 and month 36 20030216 study visits) * Currently receiving any investigational product other than denosumab or having received any investigational product during the 20030216 study * Current use of the following osteoporosis agents: bisphosphonates, calcitonin, fluoride, parathyroid hormone, selective estrogen receptor modulators, systemic oral or transdermal estrogen (except vaginal preparations and estrogen creams which are acceptable), strontium, or tibolone * For bone biopsy sub-study subjects only: known or suspected sensitivity or contraindication to tetracycline derivatives

Outcomes

Primary Outcomes

Number of Participants With Adverse Events (AEs)

A serious adverse event (SAE) is defined as an adverse event that: • is fatal • is life threatening • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • is a congenital anomaly/birth defect • is other significant medical hazard. Treatment-related adverse events includes only events for which the investigator indicated there was a reasonable possibility they may have been caused by study drug. The following were classified as adverse events of interest (events that are considered to be identified or potential risks of denosumab treatment): positively adjudicated osteonecrosis of the jaw, positively adjudicated atypical femoral fracture, hypocalcemia, adverse events potentially related to hypersensitivity, serious infection (including bacterial cellulitis), malignancy, cardiac disorders, vascular disorders, fracture healing complications, eczema, acute pancreatitis, and musculoskeletal pain.

Time frame: 84 months

Number of Participants With Laboratory Toxicities of Grade ≥ 3

Laboratory toxicity grading was based on Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Grade 3 indicates severe toxicity and Grade 4 indicates life-threatening toxicity.

Time frame: 84 months

Number of Participants With Antibodies to Denosumab

Time frame: Every 12 months through Month 84

Secondary Outcomes

Percent Change From Baseline in Lumbar Spine Bone Mineral Density by Visit

Lumbar spine bone mineral density (BMD) was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.

Time frame: Baseline (of extension study) and months 12, 24, 36, 60 and 84

Percent Change From Baseline in Total Hip Bone Mineral Density by Visit

Total hip bone mineral density was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Time frame: Baseline (of extension study) and months 12, 24, 36, 60 and 84

Percent Change From Baseline in Femoral Neck Bone Mineral Density by Visit

Femoral neck bone mineral density was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.

Time frame: Baseline (of extension study) and months 12, 24, 36, 60 and 84

Percent Change From Baseline in 1/3 Radius Bone Mineral Density by Visit

1/3 radius bone mineral density was measured in a subset of participants by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.

Time frame: Baseline (of extension study) and months 12, 24, 36, 60 and 84

Percent Change From Study 20030216 Baseline in Lumbar Spine Bone Mineral Density by Visit

Lumbar spine bone mineral density was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. Measurements at some time points during the core study 20030216 were only taken in a subset of participants.

Time frame: Study 20030216 baseline and extension study months 12, 24, 36, 60 and 84

Percent Change From Study 20030216 Baseline in Total Hip BMD by Visit

Total hip bone mineral density was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. Measurements at some time points during the core study 20030216 were only taken in a subset of participants.

Time frame: Study 20030216 baseline and extension study months 12, 24, 36, 60 and 84

Percent Change From Study 20030216 Baseline in Femoral Neck BMD by Visit

Femoral neck bone mineral density was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. Measurements at some time points during the core study 20030216 were only taken in a subset of participants.

Time frame: Study 20030216 baseline and extension study months 12, 24, 36, 60 and 84

Percent Change From Study 20030216 Baseline in 1/3 Radius BMD by Visit

1/3 radius BMD was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center. Measurements at some time points during the core study 20030216 were only taken in a subset of participants.

Time frame: Study 20030216 baseline and extension study months 12, 24, 36, 60, and 84

Number of Participants With New Vertebral Fractures

A new vertebral fracture, assessed by lateral spine X-ray using Genant semiquantitative scoring method, was identified as an ≥ 1 grade increase from the previous grade of 0 in any vertebra from T4 to L4, excluding any fracture associated with high trauma severity or a pathologic fracture.

Time frame: 84 months

Number of Participants With Non-Vertebral Fractures

Non-vertebral fractures (osteoporotic) were defined as a fracture present on a copy of radiographs or other diagnostic images such as computerized tomography (CT) or magnetic resonance imaging (MRI) confirming the fracture, and/or documented in a copy of the radiology report, surgical report, or discharge summary, excluding skull, facial, mandible, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, metacarpus, finger phalanges, and toe phalanges. In addition, fractures associated with high trauma severity or pathologic fractures were excluded.

Time frame: 84 months

Percent Change From Baseline in C-Telopeptide 1 (CTX-1) by Visit

Bone turnover markers were collected in a subset of participants who participated in the 20030216 Bone Marker sub-study and in new participants continuing beyond month 24 who were not previously in the Bone Turnover Markers sub-study.

Time frame: Baseline (of extension study), day 10, and months 6, 12, 24, 36, 48, 60, 72, and 84

Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) by Visit

Bone turnover markers were collected in a subset of participants who participated in the 20030216 Bone Marker sub-study and in new sparticipants continuing beyond month 24 who were not previously in the Bone Turnover Markers sub-study.

Time frame: Baseline (of extension study), day 10, and months 6, 12, 24, 36, 48, 60, 72, and 84

Percent Change From Study 20030216 Baseline in CTX-1 by Visit

Time frame: Study 20030216 Baseline and extension study day 10, and months 6, 12, 24, 36, 48, 60, 72, and 84

Percent Change From Study 20030216 Baseline in P1NP by Visit

Time frame: Study 20030216 Baseline and extension study day 10, and months 6, 12, 24, 36, 48, 60, 72, and 84

Percent Change From Baseline in Albumin-adjusted Serum Calcium at Day 10

Time frame: Baseline (of extension study) and day 10

Serum Denosumab Concentration

Serum concentrations of denosumab were measured by a validated conventional sandwich enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 0.8 ng/mL. Values of 0 in the table below indicate data below the lower limit of quantification.

Time frame: Baseline (pre-dose in extension study), day 10, and Months 3, 4 and 6 (pre-dose)

Bone Histomorphometry: Cancellous Bone Volume

Bone biopsy samples were prepared according to standard procedures for bone histomorphometry. Cancellous (trabecular) bone volume is the percent of the total marrow cavity that is occupied by cancellous bone (both mineralized and non-mineralized) measured by quantitative histomorphometry.