Study to Assess the Efficacy and Safety of Romosozumab Treatment Compared to Alendronate in Postmenopausal Women with Osteoporosis

• Register: EUCTR
• Last refreshed on: 30 April 2019
• Main ID: EUCTR2011-003142-41-GB
• Date of registration: 25/05/2012
• Prospective Registration: Yes
• Primary sponsor: Amgen, Inc.
• Public title: Study to Assess the Efficacy and Safety of Romosozumab Treatment Compared to Alendronate in Postmenopausal Women with Osteoporosis
• Scientific title: A Multicenter, International, Randomized, Double-blind, Alendronate-controlled Study to Determine the Efficacy and Safety of Romosozumab in the Treatment of Postmenopausal Women With Osteoporosis
• Date of first enrolment: 31/05/2012
• Target sample size: 4000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-003142-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Czech Republic, Denmark, Dominican Republic, Estonia, Finland, France, Germany, Greece, Guatemala, Hong Kong, Hungary, Ireland, Israel, Italy, Latvia, Lithuania, Mexico, Netherlands, New Zealand, Norway, Peru, Poland, Romania, Russian Federation, Slovakia, South Africa, Spain, Sweden, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: IHQ-Medical Info - Clinical Trials
• Affiliation: Amgen (Europe) GmbH

• Name: IHQ-Medical Info - Clinical Trials
• Affiliation: Amgen (Europe) GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
4.1.1 Ambulatory postmenopausal women, age = 55 to = 90 years at randomization. Postmenopausal status is defined as no vaginal bleeding or spotting for 12 consecutive months prior to screening.
4.1.2 Subject meets at least one of the following BMD and fracture criteria
BMD T-score = -2.50 at the total hip or femoral neckAND EITHER at least one moderate (SQ2) or severe (SQ3) vertebral
fracture OR at least 2 mild (SQ1) vertebral fractures
or
BMD T-score = -2.00 at the total hip or femoral neck AND EITHER at least 2 moderate (SQ2) or severe (SQ3) vertebral fractures OR a fracture of the proximal femur that occurred within 3 to 24 months prior to randomization
BMD T-scores at the time of screening will be assessed by the central imaging vendor based on DXA scans and using data for Caucasian women from the National Health and Nutritional Examination Survey (NHANES) 1998.
Vertebral fractures at the time of screening will be assessed by the
central imaging vendor based on lateral spine x-rays.
History of proximal femur fracture will be assessed by the principal
investigator based on discharge summary, radiology report, or
comparable documentation of type and date of fracture
4.1.3 At least one hip is evaluable by DXA, as assessed by the principal investigator
4.1.4 Subject has provided informed consent
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 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3850

Exclusion criteria:
Strontium ranelate,or fluoride (for osteoporosis): more than 1 month of cumulative use within 5 years prior to randomization
IV bisphosphonates
•Zoledronic acid:
-any dose received within 3 years prior to randomization
-more than 1 dose received within 5 years prior to randomization
•IV ibandronate or IV pamidronate:
-any dose received within 12 months prior to randomization
-more than 3 years of cumulative use, unless last dose received = 5 years prior to randomization
Oral bisphosphonates:
•More than 3 years of cumulative use, unless last dose received = 5 years prior to randomization
•Any dose received within 3 months prior to randomization
•More than 1 month of cumulative use between 3 and 12 months prior to randomization
Denosumab or any cathepsin K inhibitor,such as odanacatib:any dose received within 18 months prior to randomization
Teriparatide or any PTH analogs:
•any dose received within 3 months prior to randomization
•more than 1 month of cumulative use between 3 and 12 months prior to randomization
Systemic oral or transdermal estrogen or SERMs:more than 1 month of cumulative use within 6 months prior to randomization
Hormonal ablation therapy: more than 1 month of cumulative use within 6 months prior to randomization
Tibolone, cinacalcet or calcitonin:any dose received within 3 months prior to randomization
Systemic glucocorticosteroids: = 5 mg prednisone equivalent per day for more than 14 days within 3 months prior to randomization
History of metabolic or bone disease (except osteoporosis) that may interfere with the interpretation of the results, such as sclerosteosis, Paget’s disease, osteomalacia, osteogenesis imperfecta, osteopetrosis, ankylosing spondylitis, Cushing’s disease, hyperprolactinemia, and malabsorption syndrome
History of solid organ or bone marrow transplants
-25(OH) vitamin D levels <20 ng/mL as assessed by the central laboratory.
Current hyper- or hypocalcemia, defined as albumin-adjusted serum calcium outside the normal range, as assessed by the central laboratory. Serum calcium levels may be retested once in case of an elevated serum calcium level within 1.1x the ULN as assessed by the central laboratory.
Current, uncontrolled hyper- or hypothyroidism, per subject report or chart review. Uncontrolled hyperthyroidism is defined as TSH and T4 outside the normal range. Uncontrolled hypothyroidism is defined as TSH>10
Current, uncontrolled hyperparathyroidism or history of hypoparathyroidism, per subject report or chart review. Uncontrolled hyperparathyroidism is defined as: PTH outside the normal range in subjects with concurrent hypercalcemia; or PTH values >20% above the ULN in normocalcemic subjects
Possible diagnosis of multiple myeloma or related lymphoproliferative disorder, as assessed by serum protein electrophoresis performed by the local laboratory
Exclusion criteria related to contraindications or possible signs of intolerance to ALN; contraindications and potential signs of intolerance for ALN therapy include:


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Therapeutic area: Body processes [G] - Bones and nerves physological processes [G11]

Postmenopausal osteoporosis
MedDRA version: 19.1 Level: PT Classification code 10031285 Term: Osteoporosis postmenopausal System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Product Name: Romosozumab
Product Code: AMG785
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Romosozumab
Current Sponsor code: AMG785
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 210-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Trade Name: FOSAMAX
Product Name: FOSAMAX
Pharmaceutical Form: Tablet
Other descriptive name: ALENDRONATE SODIUM TRIHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 70-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): During the primary analysis period
• Subject incidence of clinical fracture (nonvertebral fracture and clinical vertebral fracture) at primary analysis
• Subject incidence of new vertebral fracture through Month 24

Timepoint(s) of evaluation of this end point: Month 24

Main Objective: For the primary analysis period (randomization to primary analysis)
• To assess the effect of romosozumab treatment for 12 months followed by alendronate (ALN) treatment compared with ALN treatment alone on the subject incidence of clinical fracture (nonvertebral fracture and clinical vertebral fracture) in postmenopausal women with osteoporosis
• To assess the effect of romosozumab treatment for 12 months followed by ALN treatment compared with ALN treatment alone on the subject incidence of new vertebral fracture in postmenopausal women with osteoporosis

Secondary Objective: Primary analysis period To assess the effect of romosozumab treatment for 12months followed by ALN treatment vs ALN treatment alone on:
•Subject incidence of fractures (all fractures [nonvertebral(…)] new… fracture [pelvis(…) hip],(…) fracture and clinical vertebral fracture) 12month double-blind ALN-controlled study period
To assess the effect of romosozumab treatment for 12months vs ALN
treatment on:
•Subject incidence of fractures (clinical fracture [nonvertebral(…)](…)[nonvertebral(…) fractures] nonvertebral fracture, hip fracture, clinical vertebral fracture, and major osteoporotic fracture [hip, forearm, humerus, and clinical vertebral])
Overall study period-randomization to end of study
To assess the effect of romosozumab treatment for 12months followed by ALN treatment vs ALN treatment alone on subject incidence of hip fracture, major nonvertebral fracture [pelvis, distal femur, proximal tibia, ribs, proximal humerus, forearm and hip](…)
See PA5 for complete wording

Secondary Outcome(s)

Secondary end point(s): During the primary analysis period
• Subject incidence of nonvertebral fracture at primary analysis
• Subject incidence of all fractures (nonvertebral fracture and new or worsening vertebral fracture) at primary analysis
• Subject incidence of new or worsening vertebral fracture through Month 24
• Subject incidence of major nonvertebral fracture (pelvis, distal femur, proximal tibia, ribs, proximal humerus, forearm, and hip) at primary analysis
• Subject incidence of hip fracture at primary analysis
• Subject incidence of multiple new or worsening vertebral fractures through Month 24
•Subject incidence of clinical fracture (nonvertebral fracture and clinical vertebral fracture) through Month 24
•Subject incidence of nonvertebral fracture through Month 24
•Subject incidence of hip fracture through Month 24
•Subject incidence of clinical vertebral fracture through Month 24• Percent change from baseline in BMD at the lumbar spine, total hip, and femoral neck at Months 24 and 36
During the 12-month double-blind ALN-controlled study period
• Subject incidence of clinical fracture (nonvertebral fracture and clinical vertebral fracture) through Month 12
• Subject incidence of new vertebral fracture through Month 12
• Subject incidence of all fractures (nonvertebral fracture and new or worsening vertebral fracture) through Month 12
• Subject incidence of nonvertebral fracture through Month 12
• Subject incidence of hip fracture through Month 12
• Subject incidence of major osteoporotic fracture (hip, forearm, humerus, and clinical vertebral) through Month 12
• Subject incidence of clinical vertebral fracture through Month 12
• Percent change from baseline in BMD at the lumbar spine, total hip and femoral neck at Month 12
For the overall study period
• Subjects incidence of nonvertebral fracture at final analysis (after 440 events)
•Subject incidence of major nonvertebral fracture (pelvis, distal femur, proximal tibia, ribs, proximal humerus, forearm, and hip) at final analysis
•Subject incidence of hip fracture at final analysis

Timepoint(s) of evaluation of this end point: Month 12 and 24

Secondary ID(s)

20110142

2011-003142-41-IT

Source(s) of Monetary Support

Amgen, Inc

UCB Inc

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 15/07/2018
• Date Completed: 29/06/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-003142-41/results