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

Phase 2
Completed
Conditions
Osteoporosis
Interventions
Drug: rhBMP-2/CPM injection and bisphosphonates, calcium, and vitamin D (oral bisphosphonate therapy)
Drug: bisphosphonates, calcium, and vitamin D
Registration Number
NCT00752557
Lead Sponsor
Pfizer
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
50
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.
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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1rhBMP-2/CPM injection and bisphosphonates, calcium, and vitamin D (oral bisphosphonate therapy)rhBMP-2/CPM , 1.0 mg/mL
3bisphosphonates, calcium, and vitamin DOral bisphosphonate therapy (standard of care)
2rhBMP-2/CPM injection and bisphosphonates, calcium, and vitamin D (oral bisphosphonate therapy)rhBMP-2/CPM , 2.0 mg/mL
Primary Outcome Measures
NameTimeMethod
Timecourse Distribution of Volumetric Bone Mineral Density (BMD) for the Hip Under Study (HUS). Volume of Interest: Femoral NeckAt Month 12

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.

Change From Baseline in Bone Mineral Density (BMD) Measured by Dual-Energy X-ray Absorptiometry (DXA)Baseline, 12 months post dose

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.

Time Course Distribution of Volumetric BMD for the Hip Under Study (HUS) for Total HipAt Month 12

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 \[CPM\]).

Secondary Outcome Measures
NameTimeMethod
Summary of Volumetric Density of Cortical and Trabecular Bone Calculated by Quantitative Computed Tomography (vQTC)24 months

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.

Number of Participants With Any Significant Changes in Serum Biomarkers of Bone Turnover From BaselineBaseline up to 12 months

Participants with significant change in serum biomarkers of bone formation and resorption from baseline are reported. Significant changes were judged by investigator.

Percentage Change From Baseline in Areal Bone Mineral Density (BMD) for Contralateral Total Hip36 months

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.

Number Participant Responses to Injectability Questionnaire Injected PopulationParticipants were monitored after treatment administration (dosing period)

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.

Trial Locations

Locations (34)

Florida Arthritis & Osteoporosis Center

🇺🇸

Port Richey, Florida, United States

Victoria Park Imaging

🇺🇸

DeLand, Florida, United States

Suncoast Clinical Research Inc

🇺🇸

New Port Richey, Florida, United States

Shrock Orthopedic Research

🇺🇸

Fort Lauderdale, Florida, United States

University Orthopedics Center

🇺🇸

State College, Pennsylvania, United States

Andre Dumont Ziekenhuis - ZOL, Campus Andre Dumont

🇧🇪

Waterschei (Genk), Belgium

Westside Regional Medical Center

🇺🇸

Plantation, Florida, United States

Tucson Orthopaedic Institute

🇺🇸

Tucson, Arizona, United States

Cool Spring Interventional, PLLC

🇺🇸

Franklin, Tennessee, United States

Instituto Palacios de Salud y Medicina de la Mujer

🇪🇸

Madrid, Spain

Arizona Research Center, Inc.

🇺🇸

Phoenix, Arizona, United States

John C. Lincoln Hospital - Deer Valley

🇺🇸

Phoenix, Arizona, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

Center for Women's Health Research at Meharry Medical College

🇺🇸

Nashville, Tennessee, United States

UC Davis Medical Center

🇺🇸

Sacramento, California, United States

Florida Hospital Deland

🇺🇸

DeLand, Florida, United States

Florida Orthopaedic Associates, P.A.

🇺🇸

DeLand, Florida, United States

Coastal orthopedic and Sports Medicine

🇺🇸

New Port Richey, Florida, United States

Florida Research Associates, LLC

🇺🇸

DeLand, Florida, United States

Columbia University Medical Center

🇺🇸

New York, New York, United States

Center for Advanced Medicine

🇺🇸

Saint Louis, Missouri, United States

Radiologica, Pracownia Rezonansu Magnetycznego i Tomografii Komputerowej

🇵🇱

Warsaw, Mazowieckie, Poland

Universitair Ziekenhuis Gent

🇧🇪

Gent, Belgium

Clinica Ruber

🇪🇸

Madrid, Spain

Prairie Lakes Healthcare Systems

🇺🇸

Watertown, South Dakota, United States

Intensive Research Unit

🇺🇸

Saint Louis, Missouri, United States

Diagnostic Professionals, Inc.

🇺🇸

Fort Lauderdale, Florida, United States

Medical Center of Trinity

🇺🇸

Trinity, Florida, United States

Creighton University Osteoporosis Research Center

🇺🇸

Omaha, Nebraska, United States

Brown Clinic

🇺🇸

Watertown, South Dakota, United States

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

Synexus Polska Sp. z o.o.

🇵🇱

Warszawa, Mazowieckie, Poland

Centralny Szpital Kliniczny MSWiA, Zaklad Diagnostyki Radiologicznej

🇵🇱

Warszawa, Mazowieckie, Poland

Creighton University Medical Center

🇺🇸

Omaha, Nebraska, United States

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