A Study to Evaluate the Effect of Treatment with AMG 785 in Postmenopausal Women with Osteoporosis Previously Treated with BisphosphonateTherapy

• Register: EUCTR
• Last refreshed on: 17 August 2015
• Main ID: EUCTR2012-002948-24-BE
• Date of registration: 28/03/2013
• Prospective Registration: Yes
• Primary sponsor: Amgen, Inc.
• Public title: A Study to Evaluate the Effect of Treatment with AMG 785 in Postmenopausal Women with Osteoporosis Previously Treated with BisphosphonateTherapy
• Scientific title: An Open-label, Randomized, Teriparatide-controlled Study to Evaluate the Effect of Treatment with AMG 785 in Postmenopausal Women with Osteoporosis Previously Treated with Bisphosphonate Therapy - STRUCTURE
• Date of first enrolment: 08/04/2013
• Target sample size: 400
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002948-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no 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

Countries of recruitment

Argentina, Belgium, Canada, Colombia, Czech Republic, Denmark, Hungary, Poland, Spain, 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:
- Ambulatory, postmenopausal women, aged = 55 to = 90 at randomization. Postmenopause is defined as no vaginal bleeding or spotting for 12 consecutive months prior to screening.
- Received oral bisphosphonate therapy at a dose approved for
postmenopausal osteoporosis for at least 3 years immediately prior to screening.
- At least 75% compliant (as reported by the subject) with bisphosphonate administration over the previous 3 years immediately prior to screening.
- At least 75% compliant (as reported by the subject) with alendronate (70 mg weekly or equivalent) administration during the 1 year immediately prior to screening.
- BMD T-score = -2.50 at the lumbar spine, total hip or femoral neck, as assessed by the central imaging vendor at the time of screening, based on DXA scans.
- History of nonvertebral fracture after age 50, or vertebral fracture.
- At least 2 vertebrae in the L1-L4 region and at least one hip that are evaluable by DXA
- 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 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 300

Exclusion criteria:
- Use of the following agents affecting bone metabolism:
• 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
• Denosumab or any cathepsin inhibitor, sucha as odanacatib (MK-0822): dose received within 18 months prior to randomization
• TPTD or any PTH analogs: more than 12 months of cumulative use or dose received within 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: 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 study results, such as sclerosteosis, Paget's disease, rheumatoid arthritis, osteomalacia, osteogenesis imperfecta, osteopetrosis, ankylosing spondylitis, Cushing's disease, hyperprolactinemia, and malabsorption syndrome
- Vitamin D insufficiency, defined as 25 (OH) vitamin D levels < 20 ng/mL, as determined by the central laboratory. Vitamin D repletion will be permitted and subjects may be rescreened.
- Current hyper- or hypocalcemia, defined as albumin adjusted serum calcium outside the normal range, as determined by the central laboratory. Albumin-adjusted serum calcium levels may be retested once in case of an elevated albumin-adjusted 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 and thyroxine 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
- Subjects with reported history of hearing loss associated with cranial nerve VIII compression due to excessive bone growth (eg, as seen in conditions such as Paget's disease, sclerosteosis and osteopetrosis)
- History of solid organ or bone marrow transplants
- Known to have human immunodeficiency virus hepatitis C virus, or hepatitis B infection
TPTD-related exclusion criteria (for all subjects)
- Hypersensitivity to TPTD or any of the excipients (eg, glacial acetic acid, sodium acetate, mannitol, metacresol, hydrochloric acid, sodium hydroxide)
- Severe renal impairment, (as assessed by the central laboratory based on a derived creatinine clearance of < 35 mL/min using the Modification of Diet in Renal Disease equation [Levey et al, 2006]). The estimated glomerular filtration rate is calculated as follows: estimated glomerular filtration rate (mL/min/1.73m2) = 175 x [Serum creatinine (mg/dL)]-1.154 x [Age]-0.203 x [0.742 if subject is female] x [1.212 if subject is
black].
- Unexplained elevations of alkaline phosphatase (> 1.5x ULN)
- Skeletal malignancies or b

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

Health Condition(s) or Problem(s) studied

Post Menopausal Osteoporosis
MedDRA version: 16.1 Level: PT Classification code 10031285 Term: Osteoporosis postmenopausal System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

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

Intervention(s)

Product Code: AMG785
Pharmaceutical Form: Solution for injection in pre-filled syringe
Current Sponsor code: AMG785
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 70-

Trade Name: Forsteo
Product Name: Forsteo
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: TERIPARATIDE
CAS Number: 52232-67-4
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 250-

Primary Outcome(s)

Primary end point(s): The primary endpoint is the percent change from baseline in DXA BMD at the total hip through Month 12.

Secondary Objective: Evaluate the effect of treatment with AMG 785 for 12 months, compared with TPTD, on the following:
• integral and cortical BMD at the total hip, as assessed by quantitative computed tomography (QCT)
• QCT bone mineral content (BMC) and estimated strength by finite element analysis (FEA) at the total hip
• BMD by DXA at the femoral neck and lumbar spine

Main Objective: Evaluate the effect of treatment with AMG 785 for 12 months, compared with teriparatide (TPTD), on total hip bone mineral density (BMD), as assessed by dual energy X-ray
absorptiometry (DXA), in postmenopausal women with osteoporosis, previously treated with bisphosphonate (BP) therapy.

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

Secondary Outcome(s)

Secondary end point(s): Key secondary endpoints, which will be included in the test sequence, are as follows:
• Percent change from baseline in BMD by DXA at the total hip at Month 6
• Percent change from baseline in BMD by DXA at the total hip at Month 12
• Percent change from baseline in cortical BMD by QCT at the total hip at Month 6
• Percent change from baseline in cortical BMD by QCT at the total hip at Month 12
• Percent change from baseline in BMD by QCT at the total hip at Month 6
• Percent change from baseline in BMD by QCT at the total hip at Month 12
• Percent change from baseline in estimated strength by FEA at the total hip at Month 6
• Percent change from baseline in estimated strength by FEA at the total hip at Month 12
Other secondary endpoints, which will not be included in the test sequence, are as follows:
• Percent change from baseline in QCT BMC at the total hip at Month 6 and Month 12
• Percent change from baseline in BMD by DXA at the femoral neck at Month 6 and Month 12
• Percent change from baseline in BMD by DXA at the lumbar spine at Month 6 and Month 12

Timepoint(s) of evaluation of this end point: Month 6 and Month 12

Secondary ID(s)

20080289

Source(s) of Monetary Support

UCB

Amgen Inc.