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

Osteoporosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00752557
• Other study ID #: 3100N0-2213
• Secondary ID: B19210022007-007
• Status: Completed
• Phase: Phase 2
• Start date: December 3, 2008
• Est. completion date: April 24, 2015

Study information

• Verified date: March 2020
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: April 24, 2015
• Est. primary completion date: April 24, 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 65 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Osteoporosis

Intervention

Drug:
• rhBMP-2/CPM injection and bisphosphonates, calcium, and vitamin D (oral bisphosphonate therapy)
Single, unilateral intraosseous injection of 6mL of rhBMP-2/CPM , 1.0 mg/mL.
• rhBMP-2/CPM injection and bisphosphonates, calcium, and vitamin D (oral bisphosphonate therapy)
Single, unilateral intraosseous injection of 6mL of rhBMP-2/CPM , 2.0 mg/mL.
• bisphosphonates, calcium, and vitamin D
Oral bisphosphonate therapy

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Andre Dumont Ziekenhuis - ZOL, Campus Andre Dumont	Waterschei (Genk)
Poland	Radiologica, Pracownia Rezonansu Magnetycznego i Tomografii Komputerowej	Warsaw	Mazowieckie
Poland	Centralny Szpital Kliniczny MSWiA, Zaklad Diagnostyki Radiologicznej	Warszawa	Mazowieckie
Poland	Synexus Polska Sp. z o.o.	Warszawa	Mazowieckie
Spain	Clinica Ruber	Madrid
Spain	Instituto Palacios de Salud y Medicina de la Mujer	Madrid
United States	University Orthopedics Center	Altoona	Pennsylvania
United States	Florida Hospital Deland	DeLand	Florida
United States	Florida Orthopaedic Associates, P.A.	DeLand	Florida
United States	Florida Research Associates, LLC	DeLand	Florida
United States	Victoria Park Imaging	DeLand	Florida
United States	Duke University Medical Center	Durham	North Carolina
United States	Diagnostic Professionals, Inc.	Fort Lauderdale	Florida
United States	Shrock Orthopedic Research	Fort Lauderdale	Florida
United States	Cool Spring Interventional, PLLC	Franklin	Tennessee
United States	Center for Women's Health Research at Meharry Medical College	Nashville	Tennessee
United States	Coastal orthopedic and Sports Medicine	New Port Richey	Florida
United States	Suncoast Clinical Research Inc	New Port Richey	Florida
United States	Columbia University Medical Center	New York	New York
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Creighton University Osteoporosis Research Center	Omaha	Nebraska
United States	Arizona Research Center, Inc.	Phoenix	Arizona
United States	John C. Lincoln Hospital - Deer Valley	Phoenix	Arizona
United States	Westside Regional Medical Center	Plantation	Florida
United States	Florida Arthritis & Osteoporosis Center	Port Richey	Florida
United States	UC Davis Medical Center	Sacramento	California
United States	Center for Advanced Medicine	Saint Louis	Missouri
United States	Intensive Research Unit	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University Orthopedics Center	State College	Pennsylvania
United States	Medical Center of Trinity	Trinity	Florida
United States	Tucson Orthopaedic Institute	Tucson	Arizona
United States	Brown Clinic	Watertown	South Dakota
United States	Prairie Lakes Healthcare Systems	Watertown	South Dakota

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Belgium,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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)
Secondary	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
Secondary	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

External Links

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