Study Evaluating Changes In Bone Mineral Density (BMD), And Safety Of Rhbmp-2/CPM In Subjects With Decreased BMD

Study Overview
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Brief Summary
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The main purpose of this study is to assess whether a locally-administered rhBMP-2/CPM injection can rapidly increase bone mass in subjects at high risk for osteoporotic fractures of the hip. All subjects will receive standard treatment for low bone mass, consisting of bisphosphonates, calcium, and vitamin D (all taken by mouth). Subjects that are randomly selected to receive treatment with rhBMP-2 will receive an injection directly into the hip. The injection is given in a surgery room using a light anesthesia.

Official Title
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A PHASE 2, MULTICENTER, RANDOMIZED, ACTIVE-CONTROLLED, PARALLEL-GROUP, DOSE-FINDING AND SAFETY STUDY OF RECOMBINANT HUMAN BONE MORPHOGENETIC PROTEIN-2 (RHBMP-2)/CALCIUM PHOSPHATE MATRIX(CPM) IN SUBJECTS WITH DECREASED BONE MINERAL DENSITY

Conditions
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Osteoporosis

Intervention / Treatment
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* Drug: rhBMP-2/CPM injection and bisphosphonates, calcium, and vitamin D (oral bisphosphonate therapy)
* Drug: rhBMP-2/CPM injection and bisphosphonates, calcium, and vitamin D (oral bisphosphonate therapy)
* Drug: bisphosphonates, calcium, and vitamin D


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Community-dwelling, ambulatory (with or without assistive device), postmenopausal females, age greater than 65 years. BMD T-score (total hip or femoral neck) of -2.5 or less in at least 1 hip. Subjects with BMD T-scores of -2.0 or less may be enrolled if at least one of the following risk factors is also present: Age greater than 75 years Family (maternal) history of fragility fracture Previous fragility fracture (self) after age 45 Subjects may either be treatment naïve or on a previously-established regimen ( greater than 1year, but less than 5 years duration) of bisphosphonate therapy. Subjects must be willing to comply with 1of the 3 protocol-designated oral bisphosphonates (risedronate, alendronate, or ibandronate sodium) with risedronate considered as first-line therapy. Exclusion Criteria: Metabolic bone disorder or disease affecting bone and mineral metabolism (eg, Paget's disease, vitamin D deficiency [ less than 20 ng/mL], hyperparathyroidism, renal osteodystrophy, osteomalacia, hypocalcemia, hypercalcemia). Coagulopathy and/or history of venous thromboembolic events (deep vein thrombosis, pulmonary embolus, retinal vein thrombosis) within the past 12 months. Inflammatory arthritis including rheumatoid, psoriatic, or crystal-induced (gouty) arthritis, or those associated with systemic lupus erythematosus (SLE), spondyloarthropathy, Reiters syndrome, or Crohns disease.

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>rhBMP-2/CPM , 1.0 mg/mL | Drug: rhBMP-2/CPM injection and bisphosphonates, calcium, and vitamin D (oral bisphosphonate therapy)<br>* Single, unilateral intraosseous injection of 6mL of rhBMP-2/CPM , 1.0 mg/mL.<br>|
| Experimental: 2<br>rhBMP-2/CPM , 2.0 mg/mL | Drug: rhBMP-2/CPM injection and bisphosphonates, calcium, and vitamin D (oral bisphosphonate therapy)<br>* Single, unilateral intraosseous injection of 6mL of rhBMP-2/CPM , 2.0 mg/mL.<br>|
| Active Comparator: 3<br>Oral bisphosphonate therapy (standard of care) | Drug: bisphosphonates, calcium, and vitamin D<br>* Oral bisphosphonate therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Bone Mineral Density (BMD) Measured by Dual-Energy X-ray Absorptiometry (DXA) | Evaluating local changes (expected increases) in BMD after administration of rhBMP-2/CPM, compared to those observed with systemic osteoporosis therapy alone. Alternatively, if changes in the total area surrounding the proximal femur are observed, bone mineral content (BMC) may instead be applied for the primary measure. BMD is defined as a derived measure of bone density, generated by dividing the bone mineral content value obtained from a bone densitometry technique (for example, DXA) by the total area of the region scanned. | Baseline, 12 months post dose | 
| Time Course Distribution of Volumetric BMD for the Hip Under Study (HUS) for Total Hip | Time course distribution of volumetric Bone mineral density (BMD) for hip is assessed by volumetric Quantitative Computed Tomography (vQCT) technique which is a 4-detector spiral (helical) computed tomography (CT) scanner with designated calibration phantom, obtain a CT scan of the proximal femora (bilateral simultaneous acquisition with volumetric rendering) to identify the specified region of interests (ROIs) for volumetric parameter to be quantified, reconstruct images of both hips and send reconstructed data (in electronic format). The vQCT regions of interest are cortical, the subcortical and trabecular. Cortical and the subcortical BMD are distinguished from trabecular effects. Peeled trabecular BMD reflects the subtraction of the extended CPM. Integral BMD reflects the cortical, subcortical, and peeled trabecular regions (minus the extended Calcium phosphate matrix [CPM]). | At Month 12 | 
| Timecourse Distribution of Volumetric Bone Mineral Density (BMD) for the Hip Under Study (HUS). Volume of Interest: Femoral Neck | Evaluating local changes (expected increases) in BMD after administration of rhBMP-2/CPM, compared to those observed with systemic osteoporosis therapy alone. Alternatively, if changes in the total area surrounding the proximal femur are observed, bone mineral content (BMC) may instead be applied for the primary measure. | At Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary of Volumetric Density of Cortical and Trabecular Bone Calculated by Quantitative Computed Tomography (vQTC) | Here, measurement of density of cortical and trabecular bone in various regions of interest (ROIs) in the femoral neck, proximal shaft, and individual trochanters and was calculated by Quantitative Computed Tomography (vQTC) in ROIs. | 24 months | 
| Number Participant Responses to Injectability Questionnaire Injected Population | Investigator documents preparation of the study medication evaluates injectability and product placement relative to desired location (for participants in active treatment groups). Surgeon performing the injection had to complete the questionnaire that evaluates ease of preparing the study medication, ability to administer study medication, and ability for the study medication to remain in the location it was administered. | Participants were monitored after treatment administration (dosing period) | 
| Number of Participants With Any Significant Changes in Serum Biomarkers of Bone Turnover From Baseline | Participants with significant change in serum biomarkers of bone formation and resorption from baseline are reported. Significant changes were judged by investigator. | Baseline up to 12 months | 
| Percentage Change From Baseline in Areal Bone Mineral Density (BMD) for Contralateral Total Hip | Evaluating local changes (expected increases) in BMD after administration of rhBMP-2/CPM, compared to those observed with systemic osteoporosis therapy alone. The percentage change from baseline in BMD for total hip (assessed by DXA) is presented for the contralateral (untreated) hip below. | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bone mineral density, bone morphogenetic protein, osteoporosis