Phase 2 Study of AMG 785 in Postmenopausal Women With Low Bone Mineral Density

• Conditions: Postmenopausal osteoporosis; MedDRA version: 18.0Level: PTClassification code 10031285Term: Osteoporosis postmenopausalSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2008-005991-28-DK
• Lead Sponsor: Amgen Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-05-28
• Last Update Posted: 11 April 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 400

Inclusion Criteria

To be eligible for enrollment into the 24-month AMG 785 treatment phase, subjects must meet the following criteria:

• Ambulatory, postmenopausal women (based on medical history) aged = 55 to = 85. Postmenopausal will be defined as no vaginal bleeding or spotting for at least one year. If there is uncertainty regarding menopausal status:

– Women 60 years of age and older will be considered postmenopausal

– Women 55-59 must have confirmation of serum FSH = 50 mIU/ml and serum estradiol = 20 pg/mL at screening

• Low BMD measured by Dual energy X-ray Absorptiometry (DXA) and assessed by the central imaging vendor (refer to table below for eligible BMD values).

- Subjects must have at least two evaluable vertebrae in the L1-L4 region, and at least one evaluable hip.

- Subjects must not have a BMD value at any anatomical site (lumbar spine, total hip and femoral neck) that is below the lower limit specified for that site.

- Scans will be done in duplicate and the mean of the scans from at least one anatomical site (lumbar spine, total hip or femoral neck) must meet the BMD values defined in table below.

Eligible BMD values
Lunar (g/cm2) Hologic (g/cm2)
Lumbar Spine (a) = 0.940 and = 0.760 = 0.827and = 0.662
Total Hip (b) = 0.756 and = 0.567 = 0.698 and = 0.515
Femoral Neck (b) = 0.760 and = 0.551 = 0.618 and = 0.438

a Values correspond to T-scores between -2.0 and -3.5 as determined by the manufacturer
b Values correspond to T-scores between -2.0 and -3.5 Based on data for Caucasian women from the National Health and Nutritional Examination Survey (NHANES) 1998

• Appropriate written informed consent must be obtained

Inclusion Criteria for the 12 month denosumab extension phase (Month 24 to 36)

• Normocalcemia at or after the Month 21 visit but before the Month 24.

• Appropriate written informed consent must be obtained

Inclusion Criteria for the 12-month AMG 785 retreatment phase (Month 36 to 48)

• Normocalcemia as determined by the central laboratory analysis of 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 AMG 785 treatment phase
• Subject has reached Month 36 of the study
• Appropriate written informed consent must be obtained

Inclusion Criteria for the 24-Month Follow-on Phase (Month 48 to Month 72)

- General inclusion criteria for participation in the 24-month follow-on phase
• 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 159
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 260

Exclusion Criteria

Exclusion Criteria for the 24-Month AMG 785 Treatment Phase
•History of vertebral fracture or fragility fracture of the wrist, humerus, hip or pelvis after age 50.
•History of metabolic or bone disease that may interfere with the interpretation of the results, such as Paget’s disease, rheumatoid arthritis, osteomalacia, osteogenesis imperfecta, osteopetrosis, ankylosing spondylitis, Cushing’s disease, hyperprolactinemia, and malabsorption syndrome.
•Vitamin D deficiency. Vitamin D repletion will be permitted and subjects may be re-screened once.
•Evidence of untreated hyper-/hypothyroidism, current hyper-/hypoparathyroidism, elevated transaminases as determined by the central laboratory, significantly impaired renal function as determined by a derived creatinine clearance of less than or equal 30 mL/min using the Modification of Diet in Renal Disease equation, calculated by the central laboratory.
-Current hyper-/hypocalcemia as determined by the central laboratory analysis of albumin adjusted serum calcium.
•History of spinal stenosis.
•History of facial nerve paralysis.
•Known to have tested positive for human immunodeficiency virus, hepatitis C virus, or hepatitis B surface antigen.
•Malignancy within the last 5 years.
•History of solid organ or bone marrow transplants.
•Use of the following agents affecting bone metabolism:
-Intravenous bisphosphonates at any time in the past.
-Fluoride (for osteoporosis) within the past 24 M.
-Denosumab at any time in the past.
-Bisphosphonates, parathyroid hormone or strontium within the past 12 M.
-Calcitonin, selective estrogen receptor modulators, systemic oral or transdermal estrogen or tibolone within the past 3 M.
-Systemic glucocorticosteroids within the past 3 M.
•Contraindicated or intolerant of alendronic acid therapy; contraindications and potential signs of intolerance for alendronic acid therapy include:
-Abnormalities of the esophagus and other factors which delay esophageal emptying such as stricture or achalasia.
-Inability to stand or sit upright for at least 30 minutes.
-Hypersensitivity to alendronic acid or to any of its components
-Active gastric or duodenal ulcer; history of significant gastrointestinal bleed requiring hospitalization or transfusion, or dyspepsia or gastroesophageal reflux disease that is uncontrolled by medication.
•Contraindicated or intolerant of teriparatide therapy; contraindications for teriparatide therapy include:
-Hypersensitivity to teriparatide or to any of its excipients.
-Unexplained elevations of alkaline phosphatase.
-Prior external beam or implant radiation therapy involving the skeleton.
-Bone metastases or a history of skeletal malignancies.
•Known sensitivity to mammalian cell derived drug products.
•Known intolerance to calcium supplements.
•Previous enrollment in an AMG 785 clinical study.
•Currently enrolled in or has not yet completed at least 1 M since ending other investigational device or drug trial(s).
•Any condition which in the opinion of the investigator.
-Compromises the ability of the subject to give written informed consent.
-Prevents the subject from complying with study procedures, from completing the study.
-Interferes with the interpretation of study results.

Exclusion criteria for the 12 month extension phase
•Incidence of a clinical vertebral fracture or fragility fracture of the wrist, humerus, hip or pelvis during the initial 24 M treatment phase of the study

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified