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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00523341
First received: August 30, 2007
Last updated: June 1, 2016
Last verified: June 2016
  Purpose
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.

Condition Intervention Phase
Osteopenia
Osteoporosis
Biological: Denosumab
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label, Single Arm, Extension Study to Evaluate the Long Term Safety and Sustained Efficacy of Denosumab (AMG162) in the Treatment of Postmenopausal Osteoporosis

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Number of Participants With Adverse Events (AEs) [ Time Frame: 84 months ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Laboratory Toxicities of Grade ≥ 3 [ Time Frame: 84 months ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Antibodies to Denosumab [ Time Frame: Every 12 months through Month 84 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percent Change From Baseline in Lumbar Spine Bone Mineral Density by Visit [ Time Frame: Baseline (of extension study) and months 12, 24, 36, 60 and 84 ] [ Designated as safety issue: No ]
    Lumbar spine bone mineral density (BMD) was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.

  • Percent Change From Baseline in Total Hip Bone Mineral Density by Visit [ Time Frame: Baseline (of extension study) and months 12, 24, 36, 60 and 84 ] [ Designated as safety issue: No ]
    Total hip bone mineral density was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.

  • Percent Change From Baseline in Femoral Neck Bone Mineral Density by Visit [ Time Frame: Baseline (of extension study) and months 12, 24, 36, 60 and 84 ] [ Designated as safety issue: No ]
    Femoral neck bone mineral density was measured by dual x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging center.

  • Percent Change From Baseline in 1/3 Radius Bone Mineral Density by Visit [ Time Frame: Baseline (of extension study) and months 12, 24, 36, 60 and 84 ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Study 20030216 Baseline in Lumbar Spine Bone Mineral Density by Visit [ Time Frame: Study 20030216 baseline and extension study months 12, 24, 36, 60 and 84 ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Study 20030216 Baseline in Total Hip BMD by Visit [ Time Frame: Study 20030216 baseline and extension study months 12, 24, 36, 60 and 84 ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Study 20030216 Baseline in Femoral Neck BMD by Visit [ Time Frame: Study 20030216 baseline and extension study months 12, 24, 36, 60 and 84 ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Study 20030216 Baseline in 1/3 Radius BMD by Visit [ Time Frame: Study 20030216 baseline and extension study months 12, 24, 36, 60, and 84 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With New Vertebral Fractures [ Time Frame: 84 months ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Non-Vertebral Fractures [ Time Frame: 84 months ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Baseline in C-Telopeptide 1 (CTX-1) by Visit [ Time Frame: Baseline (of extension study), day 10, and months 6, 12, 24, 36, 48, 60, 72, and 84 ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Baseline in Procollagen Type 1 N-telopeptide (P1NP) by Visit [ Time Frame: Baseline (of extension study), day 10, and months 6, 12, 24, 36, 48, 60, 72, and 84 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Baseline in Albumin-adjusted Serum Calcium at Day 10 [ Time Frame: Baseline (of extension study) and day 10 ] [ Designated as safety issue: No ]
  • Serum Denosumab Concentration [ Time Frame: Baseline (pre-dose in extension study), day 10, and Months 3, 4 and 6 (pre-dose) ] [ Designated as safety issue: No ]
    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.

  • Bone Histology [ Time Frame: Month 24 and month 84 ] [ Designated as safety issue: No ]
    Bone biopsy samples were prepared according to standard procedures for bone histology and bone histomorphometry to determine if there were any histological abnormalities in the bone. Results are reported for the number of participants with biopsies with normal bone micro-architecture: normal lamellar bone, normal mineralization, and osteoid, and biopsies with abnormal bone histology: osteomalacia, marrow fibrosis, or woven bone.


Enrollment: 4550
Study Start Date: August 2007
Study Completion Date: July 2015
Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Denosumab
Participants received a 60 mg subcutaneous injection of denosumab every 6 months for seven years.
Biological: Denosumab
Administered by subcutaneous injection once every 6 months.
Other Names:
  • AMG 162
  • Prolia

  Eligibility

Ages Eligible for Study:   60 Years to 94 Years   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00523341

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

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00523341     History of Changes
Other Study ID Numbers: 20060289 
Study First Received: August 30, 2007
Results First Received: June 1, 2016
Last Updated: June 1, 2016
Health Authority: Serbia: Medicine and Medical Devices Agency of Serbia
Slovakia: State Institiute for Drug Control
Argentina: Ministry of Health
Australia: Therapeutic Goods Administration
Austria: Bundesamt für Sicherheit im Gesundheitswesen
Belgium: Service Public Federal Sante Publiquest, Securite de la Chaine alimentaire et Environnement
Brazil: ANVISA (Agência Nacional de Vigilância Sanitária)
Brazil: Ministry of Health
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
Czech Republic: State Institute for Drug Control
Czech Republic: Statni ustav pro kontrolu leciv
Denmark: Laegemiddelstyrelsen
Estonia: State Agency of Medicines
Finland: Lääkelaitos
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul_Ehrlich-Institut Bundesamt fur Sera und Impfstoffe
Greece: National Organization for Medicines
Hungary: National Institute of Pharmacy
Italy: Local Ethics Committees
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romaina: National Medicines Agency
Romania: Romanian National Drug Agency
Argentina: ANMAT (Administracion Nacional de Medicamentos Alimentos y Tecnologia Medica)
Latvia: State Agency of Medicines
Lithuania: State Medicines Control Agency of Lithuania
Malta: Medicines Authority
Mexico: COFEPRIS
Mexico: Ministry of Health
Netherlands: CCMO (Centrale Commissie Mensgebonden Onderzoek): Central Committee Human Bound Research
Norway: Norwegian Medicines Agency
Slovakia: Štátny ústav pre kontrolu lieciv
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Amgen:
postmenopausal osteoporosis
low bone density
fractures
low bone mass

Additional relevant MeSH terms:
Osteoporosis
Bone Diseases, Metabolic
Osteoporosis, Postmenopausal
Bone Diseases
Musculoskeletal Diseases
Denosumab
Bone Density Conservation Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 28, 2016