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

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

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.

Study Overview

• Status: Completed
• Conditions: Osteoporosis
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Waterschei (Genk), Belgium, 3600
    • Andre Dumont Ziekenhuis - ZOL, Campus Andre Dumont
• Poland
  • Mazowieckie
    • Warsaw, Mazowieckie, Poland, 01-258
      • Radiologica, Pracownia Rezonansu Magnetycznego i Tomografii Komputerowej
    • Warszawa, Mazowieckie, Poland, 01-192
      • Synexus Polska Sp. z o.o.
    • Warszawa, Mazowieckie, Poland, 02-507
      • Centralny Szpital Kliniczny MSWiA, Zaklad Diagnostyki Radiologicznej
• Spain
  • Madrid, Spain, 28009
    • Instituto Palacios de Salud y Medicina de la Mujer
  • Madrid, Spain, 28006
    • Clinica Ruber
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85023
      • Arizona Research Center, Inc.
    • Phoenix, Arizona, United States, 85027
      • John C. Lincoln Hospital - Deer Valley
    • Tucson, Arizona, United States, 85712
      • Tucson Orthopaedic Institute
  • California
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
  • Florida
    • DeLand, Florida, United States, 32720
      • Florida Research Associates, LLC
    • DeLand, Florida, United States, 32720
      • Florida Hospital DeLand
    • DeLand, Florida, United States, 32720
      • Florida Orthopaedic Associates, P.A.
    • DeLand, Florida, United States, 32724
      • Victoria Park Imaging
    • Fort Lauderdale, Florida, United States, 33316
      • Shrock Orthopedic Research
    • Fort Lauderdale, Florida, United States, 33311
      • Diagnostic Professionals, Inc.
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research Inc
    • New Port Richey, Florida, United States, 34653
      • Coastal orthopedic and Sports Medicine
    • Plantation, Florida, United States, 33324
      • Westside Regional Medical Center
    • Port Richey, Florida, United States, 34668
      • Florida Arthritis & Osteoporosis Center
    • Trinity, Florida, United States, 34655
      • Medical Center of Trinity
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63110
      • Intensive Research Unit
    • Saint Louis, Missouri, United States, 63310
      • Center for Advanced Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • Creighton University Medical Center
    • Omaha, Nebraska, United States, 68131
      • Creighton University Osteoporosis Research Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16602
      • University Orthopedics Center
    • State College, Pennsylvania, United States, 16801
      • University Orthopedics Center
  • South Dakota
    • Watertown, South Dakota, United States, 57201
      • Brown Clinic
    • Watertown, South Dakota, United States, 57201G
      • Prairie Lakes Healthcare Systems
  • Tennessee
    • Franklin, Tennessee, United States, 37067
      • Cool Spring Interventional, PLLC
    • Nashville, Tennessee, United States, 37208-3599
      • Center for Women's Health Research at Meharry Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 85 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; rhBMP-2/CPM , 1.0 mg/mL	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.; Drug: 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.
Experimental: 2; rhBMP-2/CPM , 2.0 mg/mL	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.; Drug: 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.
Active Comparator: 3; Oral bisphosphonate therapy (standard of care)	Drug: bisphosphonates, calcium, and vitamin D; Oral bisphosphonate therapy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2008
• Primary Completion (Actual): April 24, 2015
• Study Completion (Actual): April 24, 2015

Study Registration Dates

• First Submitted: September 12, 2008
• First Submitted That Met QC Criteria: September 12, 2008
• First Posted (Estimate): September 15, 2008

Study Record Updates

• Last Update Posted (Actual): March 20, 2020
• Last Update Submitted That Met QC Criteria: March 7, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: osteoporosis; Bone mineral density; bone morphogenetic protein
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Calcium; Vitamins; Calcium, Dietary; Ergocalciferols; Diphosphonates
• Other Study ID Numbers: 3100N0-2213; B1921002 (Other Identifier: Alias Study Number); 2007-007456-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.