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Romosozumab (AMG 785) in Postmenopausal Women With Low Bone Mineral Density

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00896532
First received: May 7, 2009
Last updated: May 9, 2017
Last verified: May 2017
  Purpose
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.

Condition Intervention Phase
Low Bone Mineral Density Postmenopausal Osteoporosis Drug: Placebo to Romosozumab Drug: Alendronate Drug: Teriparatide Drug: Romosozumab Drug: Denosumab Drug: Placebo to Denosumab Drug: Zoledronic acid Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, 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

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • Nature, frequency and severity of adverse events and their relationship to treatment; Changes [ Time Frame: 24-36 months ]
  • 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 ]
  • Percent change from baseline and month 48 to months 51, 54, 60, 66, and 72 in BTMs. [ Time Frame: 72 months ]

Enrollment: 419
Actual Study Start Date: June 3, 2009
Study Completion Date: February 18, 2016
Primary Completion Date: February 21, 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo

Participants received placebo matching to romosozumab once a month (QM) or once every 3 months (Q3M) administered subcutaneously (SC) for up to 24 months.

Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. From months 36 to 48 participants received romosozumab 210 mg SC QM. At month 48 eligible participants received a single dose of open-label zoledronic acid 5 mg intravenously, or no intervention.

Drug: Placebo to Romosozumab
Administered by subcutaneous injection QM or Q3M.
Drug: Denosumab
Denosumab 60 mg administered by subcutaneous injection Q6M
Other Name: Prolia®
Drug: Placebo to Denosumab
Administered by subcutaneous injection Q6M
Drug: Zoledronic acid
Zoledronic acid 5 mg administered intravenously
Other Name: Aclasta
Active Comparator: Alendronate

Participants received open-label alendronate (ALN) 70 mg orally (PO) every week (QW) for 12 months. At month 12 participants transitioned to receive romosozumab 140 mg subcutaneously every month for an additional 12 months (months 12 to 24).

Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. At month 36 participants ended study participation.

Drug: Alendronate
Administered orally once a week
Other Name: Fosamax
Drug: Denosumab
Denosumab 60 mg administered by subcutaneous injection Q6M
Other Name: Prolia®
Drug: Placebo to Denosumab
Administered by subcutaneous injection Q6M
Active Comparator: Teriparatide
Participants received open-label teriparatide 20 μg subcutaneously every day (QD) for 12 months. At month 12 participants ended study participation.
Drug: Teriparatide
Teriparatide 20 μg administered by subcutaneous injection once a day
Other Name: Forsteo
Experimental: Romosozumab 70 mg QM

Participants received double-blind romosozumab 70 mg subcutaneously every month for 24 months.

Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. From months 36 to 48 participants received romosozumab 210 mg SC QM. At month 48 eligible participants received a single dose of open-label zoledronic acid 5 mg intravenously, or no intervention.

Drug: Romosozumab
Administered by subcutaneous injection
Other Names:
  • AMG 785
  • EVENITY™
Drug: Denosumab
Denosumab 60 mg administered by subcutaneous injection Q6M
Other Name: Prolia®
Drug: Placebo to Denosumab
Administered by subcutaneous injection Q6M
Drug: Zoledronic acid
Zoledronic acid 5 mg administered intravenously
Other Name: Aclasta
Experimental: Romosozumab 140 mg Q3M

Participants received double-blind romosozumab 140 mg subcutaneously once every 3 months for 24 months.

Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. From months 36 to 48 participants received romosozumab 210 mg SC QM. At month 48 eligible participants received a single dose of open-label zoledronic acid 5 mg intravenously, or no intervention.

Drug: Romosozumab
Administered by subcutaneous injection
Other Names:
  • AMG 785
  • EVENITY™
Drug: Denosumab
Denosumab 60 mg administered by subcutaneous injection Q6M
Other Name: Prolia®
Drug: Placebo to Denosumab
Administered by subcutaneous injection Q6M
Drug: Zoledronic acid
Zoledronic acid 5 mg administered intravenously
Other Name: Aclasta
Experimental: Romosozumab 140 mg QM

Participants received double-blind romosozumab 140 mg QM subcutaneously for 24 months.

Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. From months 36 to 48 participants received romosozumab 210 mg SC QM. At month 48 eligible participants received a single dose of open-label zoledronic acid 5 mg intravenously, or no intervention.

Drug: Romosozumab
Administered by subcutaneous injection
Other Names:
  • AMG 785
  • EVENITY™
Drug: Denosumab
Denosumab 60 mg administered by subcutaneous injection Q6M
Other Name: Prolia®
Drug: Placebo to Denosumab
Administered by subcutaneous injection Q6M
Drug: Zoledronic acid
Zoledronic acid 5 mg administered intravenously
Other Name: Aclasta
Experimental: Romosozumab 210 mg Q3M

Participants received double-blind romosozumab 210 mg Q3M subcutaneously for 24 months.

Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. From months 36 to 48 participants received romosozumab 210 mg SC QM. At month 48 eligible participants received a single dose of open-label zoledronic acid 5 mg intravenously, or no intervention.

Drug: Romosozumab
Administered by subcutaneous injection
Other Names:
  • AMG 785
  • EVENITY™
Drug: Denosumab
Denosumab 60 mg administered by subcutaneous injection Q6M
Other Name: Prolia®
Drug: Placebo to Denosumab
Administered by subcutaneous injection Q6M
Drug: Zoledronic acid
Zoledronic acid 5 mg administered intravenously
Other Name: Aclasta
Experimental: Romosozumab 210 mg QM

Participants received double-blind romosozumab 210 mg QM subcutaneously for 24 months.

Participants were then rerandomized to receive denosumab 60 mg or placebo to denosumab subcutaneously every 6 months from months 24 to 36. From months 36 to 48 participants received romosozumab 210 mg SC QM. At month 48 eligible participants received a single dose of open-label zoledronic acid 5 mg intravenously, or no intervention.

Drug: Romosozumab
Administered by subcutaneous injection
Other Names:
  • AMG 785
  • EVENITY™
Drug: Denosumab
Denosumab 60 mg administered by subcutaneous injection Q6M
Other Name: Prolia®
Drug: Placebo to Denosumab
Administered by subcutaneous injection Q6M
Drug: Zoledronic acid
Zoledronic acid 5 mg administered intravenously
Other Name: Aclasta

Detailed Description:

This study included a 24-month treatment phase followed by rerandomization to a 12-month extension phase with denosumab or placebo, followed by a 12-month retreatment phase with romosozumab, followed by a 24-month follow-on phase with zoledronic acid or no intervention.

  • 24-month Romosozumab Treatment Phase (months 1 to 24): Participants were randomized in a 1:1:1:1:1:1:1:1 ratio to receive 1 of 5 double-blind dosing regimens of romosozumab or placebo or open-label alendronate (ALN) or open-label teriparatide (TPTD) for the first 12 months of the study. At month 12, participants in the romosozumab and placebo groups continued their assigned treatment for an additional 12 months, participants in the TPTD group ended study participation, and participants in the ALN group transitioned to receive romosozumab 140 mg subcutaneously (SC) every month (QM) for an additional 12 months (months 12 to 24).
  • 12-month Denosumab Extension Phase (months 24 to 36): At the end of the 24-month romosozumab treatment phase, eligible participants were randomized 1:1 within their original treatment group to receive either denosumab or placebo every 6 months (Q6M) for 12 months.
  • 12-month Romosozumab Retreatment Phase (months 36 to 48): From months 36 to 48, participants initially randomized to romosozumab or placebo received romosozumab 210 mg SC QM. Participants who initially received ALN ended their participation at month 36 and were not retreated with romosozumab.
  • 24-month Follow-on Phase (months 48 to 72): At month 48, participants received 1 dose of zoledronic acid 5 mg intravenously or no intervention for an additional 24 months.
  Eligibility

Ages Eligible for Study:   55 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00896532

Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
Publications:
10.1002/jbmr.2932

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00896532     History of Changes
Other Study ID Numbers: 20060326
2008-005991-28 ( EudraCT Number )
Study First Received: May 7, 2009
Last Updated: May 9, 2017

Additional relevant MeSH terms:
Osteoporosis
Osteoporosis, Postmenopausal
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Zoledronic acid
Diphosphonates
Denosumab
Alendronate
Teriparatide
Antibodies, Monoclonal
Bone Density Conservation Agents
Physiological Effects of Drugs
Immunologic Factors

ClinicalTrials.gov processed this record on July 25, 2017