To assess the effect of AMG785 treatment for 12 months followed by alendronate treatment compared with alendronate on the incidence of clinical fracture and new vertebral fracture.
ID
Source
Brief title
Condition
- Bone disorders (excl congenital and fractures)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
For the primary analysis periode:
- To assess the effect of AMG 785 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 AMG 785 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 outcome
For the primary analysis periode:
To assess the effect of AMG 785 treatment for 12 months followed by ALN
treatment compared with ALN treatment alone on:
- Subject incidence of fractures (all fractures [nonvertebral fractures and new
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, multiple new or
worsening vertebral fracture and clinical vertebral fracture)
- Percent changes in Dual energy X-ray Absorptiometry (DXA) bone mineral
density (BMD) at the lumbar spine, total hip, and femoral neck
2) For the 12-month double-blind ALN-controlled study period
To assess the effect of AMG 785 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], nonvertebral fracture,
hip fracture, clinical vertebral fracture, and major osteoporotic fracture
[hip, forearm, humerus, and clinical vertebral])
- Percent changes in DXA BMD at the lumbar spine, total hip, and femoral neck
3) For the overall study (randomization to end of study):
- To assess the effect of AMG 785 treatment for 12 months followed by ALN
treatment compared with ALN treatment alone on subject incidence of hip
fracture, major nonvertebral fracture [pelvis, distal femur, proximal tibia,
ribs, proximal humerus, forearm, and hip], and nonvertebral fractures
Background summary
Osteoporosis is a chronic disease and despite long-term administration of
bisphosphonates, patients with severe PMO remain at increased risk of fracture
and are in need of therapies with strong efficacy and the potential to reverse
their disease condition by increasing bone formation and improving bone
structure. Approved treatments for PMO include inhibitors of bone resorption
such as selective estrogen receptor modulators (SERMs, eg, raloxifene),
bisphosphonates (eg, ALN, risedronate, ibandronate, and zoledronate),
calcitonin, denosumab, or agents that stimulate bone formation like
teriparatide. A novel bone forming agent for the treatment of PMO, with a
different mechanism of action and the potential to reverse the features of PMO
by increasing bone volume and BMD and by improving bone architecture,
ultimately resulting in increased bone strength and reduced risk for fracture,
would be a welcome new therapeutic option particularly for subjects with
significantly compromised bone strength at high risk of fracture. AMG 785 is a
humanized monoclonal antibody that is designed to bind and inhibit sclerostin,
thereby promoting osteoblast differentiation and activity, leading to an
increase in bone formation, BMD, and bone strength.
Study objective
To assess the effect of AMG785 treatment for 12 months followed by alendronate
treatment compared with alendronate on the incidence of clinical fracture and
new vertebral fracture.
Study design
The study consists of three parts. The first part will be acrried out to define
if the patient is eligible for the study (screening). The second part is the
research/study phase which will take 12 months. During this phase (and after a
positive screening outcome), patients will be randomzied (ratio 1:1) into one
of the two study arms:
1. AMG785, subcutane injection, 210 mg, every month + placebo for oral
alendronate, 70 mg, every week
2. Alendronate, oral, 70 mg, every week + placebo for AMG785, subcutane
injection, 210 mg, every month
During the study phase, patients receive daily calcium- and vitamin D
supplements.
the third part is the open label phase in which patients recieve alendronate
for at least 12 months. During this phase patients will visit the hospital but
will also be followed up by phone calls. The complete study will take 25-71
months.
In total, 4095 patients in 325 hospitals wordwide were randomized. None of the
sites in the Netherlands will participate in the PK/BTM substudy.
Intervention
Patients will receive AMG785, subcutane injection, 210 mg, every month +
placebo for oral alendronate, 70 mg, every week or alendronate, oral, 70 mg,
every week + placebo for AMG785, subcutane injection, 210 mg, every month.
Study burden and risks
The following procedures will be performed according to appendix A (schedule of
assessments) of the protocol: physical examination, vital signs, blood
sampling. DXA scans (femur and spine) will be performed at 7 visits and X-rays
of the spine will be carried out at 8 visits. Questionnaires need to be
completed at 7 visits.
Patients need to come to the hospital for 14 times during the first 12 months ,
every 3 months during the next half year and every 6 months therafter untill
the end of the study. There will be phone call visits during the study duration.
For adverse events of AMG785, please see question E9.
Minervum 7061
Breda 4800DH
NL
Minervum 7061
Breda 4800DH
NL
Listed location countries
Age
Inclusion criteria
- Ambulatory postmenopausal women, age * 55 to * 90 years
- Subject meets at least one of the following BMD and fracture criteria
* BMD T-score * -2.50 at the total hip or femoral neck (as 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) 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.
Refer to Sections 7.13 and 7.14 for details.
- At least one hip is evaluable by DXA, as assessed by the principal investigator
- Subject has provided informed consent
Exclusion criteria
- Use of the following agents affecting bone metabolism (4.2.1 through 4.2.9):
* Strontium ranelate, or fluoride (for osteoporosis): more than 1 month of cumulative use within 5 years prior to randomization
* Intravenous (IV) bisphosphonates
o Zoledronic acid: any dose received within 3 years prior to randomization
o more than 1 dose received within 5 years prior to randomization
* IV ibandronate or IV pamidronate:
o any dose received within 12 months prior to randomization
o more than 3 years of cumulative use, unless last dose received * 5 years prior to randomization
* Oral bisphosphonates:
o any dose received within 3 months prior to randomization
o more than 1 month of cumulative use between 3 and 12 months prior to randomization
o more than 3 years of cumulative use, unless last dose received * 5 years prior to randomization
* Denosumab or any cathepsin K inhibitor, such as odanacatib (MK-0822): any dose received within 18 months prior to randomization
* Teriparatide or any PTH analogs:
o any dose received within 3 months prior to randomization
o 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;
- Current hyper- or hypocalcemia, defined as albumin-adjusted serum calcium outside the normal range, 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 upper limit of normal in normocalcemic subjects;
- Possible diagnosis of multiple myeloma or related lymphoproliferative disorder, as assessed by serum protein electrophoresis performed by the local laboratory (electrophoresis results within 6 months prior to signing consent will be acceptable);
- Exclusion criteria related to contraindications or possible signs of intolerance to ALN (see protocol section 4.2.17)
- General exclusion criteria as described in protocol section 4.2.18
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-003142-41-NL |
| ClinicalTrials.gov | NCT01631214 |
| CCMO | NL39710.056.12 |