Phase 2 Study of AMG 785 in Postmenopausal Women With Low Bone Mineral Density
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Purpose
This phase 2 clinical trial will study the safety and efficacy of AMG 785, an investigational bone building agent, in the treatment of postmenopausal women with low bone mineral density. Different doses and dosing frequencies of AMG 785 will be compared to placebo in a double-blind fashion. In addition, AMG 785 will be compared to open label alendronate and open label teriparatide.
The clinical hypothesis is that AMG 785 compared with placebo will cause a greater percent change from baseline in lumbar spine bone mineral density.
At the end of the initial 24 months treatment phase, eligible subjects will enter a 12 months extension phase. Subjects will be randomized 1:1 within their original treatment group to receive either denosumab or placebo every 6 months Subjects not participating in the 12 months extension phase will be followed for an additional three months to Month 27.
At the end of the 12 month extension phase, eligible subjects will enter a 12 month retreatment phase. All subjects participating in the re-treatment phase will receive 210 mg of AMG 785 QM for 12 months. Subjects not participating in the 12 month re-treatment phase will complete the study at Month 36. At the end of the 12 month AMG 785 retreatment phase, subjects will enter a 24 month follow-on phase. Based on the outcome of the eligibility assessment, subjects will either receive one dose of 5 mg ZOL intravenously or no intervention. Subjects not participating in the 24 month follow-on phase will be followed for an additional 3 month observational period to month 51.
| Condition | Intervention | Phase |
|---|---|---|
|
Low Bone Mineral Density Postmenopausal Osteoporosis |
Drug: Active Comparator Alendronate Drug: Placebo Drug: AMG 785 Drug: Active comparator teriparatide Drug: Denosumab Drug: Zoledronic acid |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | A Randomised, Placebo-controlled, Multi-dose Phase 2 Study to Determine the Efficacy, Safety and Tolerability of AMG 785 in the Treatment of Postmenopausal Women With Low Bone Mineral Density |
- Percent change from baseline at month 12 in bone mineral density at the lumbar spine for the individual AMG 785 groups and pooled placebo arms. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Percent change from baseline at month 12 in bone mineral density at the total hip, femoral neck and distal radius for the individual AMG 785 groups and pooled placebo arms. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Percent change from baseline at month 1, 3, 6, 9 and 12 in bone turnover markers for the individual AMG 785 groups and pooled placebo arms. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Nature, frequency, severity of adverse events & their relationship to treatment; Changes from baseline in vital signs, laboratory assessments, ECG parameters; Bone histologic & histomorphometric pameters; Formation of anti-AMG 785 antibodies [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
- Percent change from baseline at month 24 in bone mineral density for the individual AMG 785 groups and pooled placebo arms. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
- Percent change from baseline in Quantitative Computed Tomography (QCT) BMD & variables for AMG 785 and teriparatide groups during the first year [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Percent change from baseline at month 6 in bone mineral density at the lumbar spine, total hip and femoral neck for the individual AMG 785 groups and pooled placebo arms. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Nature, frequency and severity of adverse events and their relationship to treatment; Changes [ Time Frame: 24-36 months ] [ Designated as safety issue: Yes ]
- Percent change from baseline and month 48 to months 54, 60, 66, and 72 in BMD at the lumbar spine, total hip, and femoral neck. [ Time Frame: 72 months ] [ Designated as safety issue: No ]
- Percent change from baseline and month 48 to months 51, 54, 60, 66, and 72 in BTMs. [ Time Frame: 72 months ] [ Designated as safety issue: No ]
| Enrollment: | 419 |
| Study Start Date: | June 2009 |
| Estimated Study Completion Date: | March 2014 |
| Primary Completion Date: | February 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: A
AMG 785 70mg or 140mg or 210mg SC or placebo SC every month (QM)
|
Drug: AMG 785
140mg SC QM
Drug: Placebo
SC QM
Drug: AMG 785
210mg SC QM
Drug: AMG 785
70mg SC QM
|
|
Active Comparator: E
Teriparatide 20ug SC every day (QD)
|
Drug: Active comparator teriparatide
20µg SC every day (QD)
|
|
Experimental: B
AMG 785 140mg or 210mg SC or placebo SC every three months (Q3M)
|
Drug: Placebo
SC Q3M
Drug: AMG 785
140mg SC Q3M
Drug: AMG 785
210mg SC Q3M
|
|
Active Comparator: D
Alendronate (Fosamax) 70mg PO every week (QW)
|
Drug: Active Comparator Alendronate
70mg PO every week (QW)
|
|
Experimental: F
Denosumab 60 mg SC or placebo SC administration every 6 months (Q6M)
|
Drug: Denosumab
60 mg SC Q6M
|
|
Experimental: G
AMG 785 210 mg SC every month (QM)
|
Drug: AMG 785
210mg SC QM
|
|
Active Comparator: H
Zoledronic acid 5 mg IV or no intervention
|
Drug: Zoledronic acid
5 mg IV
|
Eligibility| Ages Eligible for Study: | 55 Years to 85 Years |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
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: HIV, Hep-C or Hep-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 ICF 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 ICF withdrawal and discontinuation of IP 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
Contacts and Locations More Information
Additional Information:
No publications provided
| Responsible Party: | Amgen |
| ClinicalTrials.gov Identifier: | NCT00896532 History of Changes |
| Other Study ID Numbers: | 20060326 |
| Study First Received: | May 7, 2009 |
| Last Updated: | May 22, 2013 |
| Health Authority: | Argentina: Ministry of Health Austria: Central Ethics Committee Austria: Federal Ministry for Health and Women Belgium: Ministry of Health Canada: Health Canada Denmark: Central Ethics Committee Denmark: Danish Medicines Agency Spain: reference Ethics Committee Spain: Spanish Agency of Medicines United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Osteoporosis Osteoporosis, Postmenopausal Bone Diseases, Metabolic Bone Diseases Musculoskeletal Diseases Zoledronic acid |
Alendronate Teriparatide Diphosphonates Bone Density Conservation Agents Physiological Effects of Drugs Pharmacologic Actions |
ClinicalTrials.gov processed this record on June 17, 2013