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

• Register: EUCTR
• Last refreshed on: 2 October 2017
• Main ID: EUCTR2011-003142-41-LV
• Date of registration: 05/06/2012
• 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: 08/06/2012
• 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 neck AND 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
-Vitamin D insufficiency, 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 upper limit of normal as assessed by the central laboratory.
-Current, uncontrolled hyper- or hypothyroidism, defined as thyroidstimulating hormone outside of the normal range, per subject report or chart review
-Current, uncontrolled hyper- or hypoparathyroidism, defined as PTH outside the normal range, per subject report or chart review
-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:
•Hypocalcemia
• Abnormalities of the esophagus, which delay esophageal emptying such as stricture or achalasia
• Inability to stand or sit upright for at least 30 minutes
• Hypersensitivity to ALN or other constituents of ALN tablets
• Pregnancy and lactation
• Other contraindications to ALN based on the country-specific product insert applicable to the specific study center
• Significantly impaired renal function.
-General
• Subject is currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or re

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: 17.0 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 overall study period (12-month double-blind ALN-controlled study period followed by the open label ALN study period)
• Subject incidence of clinical fracture (nonvertebral fracture and clinical vertebral fracture) at primary analysis
• Subject incidence of new vertebral fracture through Month 24

Main Objective: For the overall study period (12-month double-blind alendronate [ALN]-controlled study period
followed by the open-label ALN study period)
• To assess the effect of romosozumab treatment for 12 months followed by ALN treatment compared with ALN treatment alone on the subject incidence of clinical fracture (nonvertebral fracture and clinical vertebral fracture) in women with PMO
• 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 women with PMO

Secondary Objective: To assess the effect of romosozumab treatment for 12 months followed by ALN treatment compared with ALN treatment alone on:
• Subject incidence of fractures (all fractures [nonvertebral fractures and new or worsening vertebral fractures], new or worsening vertebral fracture, nonvertebral fracture, major nonvertebral fracture [pelvis, distal femur, proximal tibia, ribs, proximal humerus, forearm, and hip], hip fracture, and multiple new or worsening vertebral fracture)
• Percent changes in Dual energy X-ray Absorptiometry (DXA) bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck
To assess the effect of romosozumab treatment for 12 months compared with ALN treatment on:
• Subject incidence of fractures (clinical fracture [nonvertebral fracture and clinical vertebral fracture], new vertebral fracture, all fractures [nonvertebral fractures and new vertebral fractures])
• Percent changes in DXA BMD at the lumbar spine, total hip, and femoral neck

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

Secondary Outcome(s)

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

Secondary end point(s): During the overall study period (12-month double-blind ALN-controlled study period followed by the open-label ALN study 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
• 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
• Percent change from baseline in BMD at the lumbar spine, total hip and femoral neck at Month 12

Secondary ID(s)

20110142

2011-003142-41-IT

Source(s) of Monetary Support

Amgen, Inc

UCB Inc