MedPath

A Study of the Impact of Methotrexate (MTX) Discontinuation on the Efficacy of Subcutaneous (SC) Tocilizumab (TCZ) With MTX

Phase 3
Completed
Conditions
Rheumatoid Arthritis
Interventions
Registration Number
NCT01855789
Lead Sponsor
Hoffmann-La Roche
Brief Summary

This randomized, multicenter, double-blind, parallel group study will evaluate the impact of MTX discontinuation on the efficacy of SC TCZ in participants with moderate to severe active rheumatoid arthritis who have an inadequate response to current MTX therapy. Participants will initiate treatment with TCZ weekly or every 2 weeks along with MTX at a stable dose orally in an open-label manner for 24 weeks. Participants with a disease activity score based on 28 joints (DAS28) less than or equal to (\</=) 3.2 at Week 24, will be randomized to either continue receiving a stable dose of MTX or to switch to matching placebo up to Week 52. Participants without a DAS28 score \</=3.2 at Week 24, will continue the same treatment in a non-randomized open-label manner up to Week 52.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
718
Inclusion Criteria
  • Body weight </=150 kg
  • Active moderate to severe rheumatoid arthritis (DAS28 >/=4.4) according to the revised 1987 ACR criteria at screening and baseline (prior to treatment on Day 1)
  • Currently receiving oral MTX for at least 24 weeks and on a stable oral dose of at least 15 mg/week for at least 6 weeks prior to treatment (Day 1), with the following exception: a stable dose of at least 10 mg/week is allowed for participants with a body weight <50 kg or calculated glomerular filtration rate (or creatinine clearance) <60 milliliters per minute (mL/min)
  • History of parenteral (SC or intramuscular [IM]) MTX is allowed, but not within 6 weeks prior to treatment (Day 1). Participants must not have a documented, clinically significant intolerance to oral MTX and must be receiving oral MTX at a dose of 15 mg/week for at least 6 weeks prior to treatment (Day 1)
  • Participants who have received one prior anti-tumor necrosis factor (TNF) must have discontinued etanercept, infliximab, certolizumab, adalimumab, or golimumab for at least 6 months prior to screening
  • Oral corticosteroids must have been </=10 mg/day prednisone (or equivalent) and stable for at least 25 out of 28 days prior to treatment (Day 1)
  • Participants receiving treatment on an outpatient basis
Exclusion Criteria
  • Documented medical history of significant intolerance to oral MTX >/=15 mg/week
  • Participants receiving other (non-MTX) disease modifying anti-rheumatic drugs (DMARDs) within 8 weeks of screening
  • Previous treatment with abatacept, rituximab, tofacitinib, or anakinra
  • Treatment with parenteral corticosteroids within 4 weeks prior to treatment
  • Previous treatment with cell-depleting therapies or alkylating agents
  • Previous treatment with TCZ
  • Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery during the study
  • Rheumatic autoimmune disease other than rheumatoid arthritis
  • Non-rheumatic active autoimmune diseases (for example, inflammatory bowel diseases, psoriasis, multiple sclerosis)
  • Prior history of or current inflammatory joint disease other than rheumatoid arthritis
  • Functional Class IV according to the revised (1987) ACR criteria for rheumatoid arthritis
  • History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
  • Evidence of significant uncontrolled concomitant diseases; uncontrolled disease states where flares are commonly treated with oral or parenteral corticosteroids
  • Active current or history of recurrent infection, or any major episode of infection requiring hospitalization or treatment with intravenous antibiotics within 4 weeks prior to screening or oral antibiotics within 2 weeks prior to screening
  • Active tuberculosis requiring treatment within the previous 3 years
  • History of or currently active primary or secondary immunodeficiency
  • Pregnant or breast-feeding women
  • Positive for hepatitis B or hepatitis C infection
  • For potential MRI substudy participants: the presence of any metal-containing device or object in the body

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Non-Randomized Participants (TCZ + MTX)Tocilizumab (TCZ)All participants will receive initial treatment with open-label TCZ + MTX. Participants who complete 24-week treatment with open-label TCZ + MTX and did not achieve a DAS28 score \</=3.2 at Week 24, will continue receiving TCZ + MTX in open label manner up to Week 52.
Randomized Participants (TCZ + MTX)Tocilizumab (TCZ)Participants who complete the initial 24-week treatment with open-label TCZ + MTX and achieve a DAS28 score \</=3.2 at Week 24, will be randomized to receive TCZ along with MTX up to Week 52.
Non-Randomized Participants (TCZ + MTX)Methotrexate (MTX)All participants will receive initial treatment with open-label TCZ + MTX. Participants who complete 24-week treatment with open-label TCZ + MTX and did not achieve a DAS28 score \</=3.2 at Week 24, will continue receiving TCZ + MTX in open label manner up to Week 52.
Randomized Participants (TCZ + MTX)Methotrexate (MTX)Participants who complete the initial 24-week treatment with open-label TCZ + MTX and achieve a DAS28 score \</=3.2 at Week 24, will be randomized to receive TCZ along with MTX up to Week 52.
Randomized Participants (TCZ + PBO)Tocilizumab (TCZ)Participants who complete the initial 24-week treatment with open-label TCZ + MTX and achieve a DAS28 score \</=3.2 at Week 24, will be randomized to receive TCZ along with MTX matched placebo (PBO) up to Week 52.
Randomized Participants (TCZ + PBO)Placebo (PBO)Participants who complete the initial 24-week treatment with open-label TCZ + MTX and achieve a DAS28 score \</=3.2 at Week 24, will be randomized to receive TCZ along with MTX matched placebo (PBO) up to Week 52.
Primary Outcome Measures
NameTimeMethod
Change From Week 24 in Disease Activity Score Based on 28 Joints (DAS28) Score at Week 40Week 24, Week 40

The DAS28 was derived from assessments of erythrocyte sedimentation rate (ESR) measured in millimeters per hour (mm/h), tender joint count on 28 joints (TJC28), swollen joint count on 28 joints (SJC28), and Patient's Global Assessment of disease activity according to 100--millimeter (mm) Visual Analog Scale (VAS). DAS28 score was calculated as \[0.56 × square root of TJC\] + \[0.28 × square root of SJC\] + \[0.70 × natural log (ESR)\] + \[0.014 × VAS\]. DAS28 score could range from 0 to 10, where higher score represented higher disease activity. The change from Week 24 to Week 40 was averaged among all participants, where negative changes indicated an improvement in disease activity.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants Achieving 70% Improvement in American College of Rheumatology (ACR70) ResponseWeeks 24, 40, and 52

The ACR70 response at any time was defined as \>/=70% improvement compared to baseline in TJC (assessed on 68 joints) and SJC (assessed on 66 joints); and 70% improvement compared to baseline in 3 of the following 5 criteria, respectively: 1) Patient's global assessment of disease activity according to 100-mm VAS, 2) Physician's global assessment of disease activity according to 100-mm VAS, 3) participant's global assessment of pain according to 100-mm VAS, 4) Participant's assessment of functional ability via HAQ-DI, and 5) Acute phase reactant (ESR in mm/h or CRP in mg/dL).

Percentage of Participants With DAS28 Score </=3.2 (Low DAS28)Week 40, Week 52

The DAS28 was derived from assessments of ESR measured in mm/h, TJC28, SJC28, and Patient's global assessment of disease activity according to 100-mm VAS. DAS28 score was calculated as \[0.56 × square root of TJC\] + \[0.28 × square root of SJC\] + \[0.70 × natural log (ESR)\] + \[0.014 × VAS\]. DAS28-ESR score could range from 0 to 10, where higher score represented higher disease activity.

Percentage of Participants Achieving 20% Improvement in American College of Rheumatology (ACR20) ResponseWeeks 24, 40, and 52

The ACR20 response at any time was defined as \>/=20% improvement compared to baseline in TJC (assessed on 68 joints) and SJC (assessed on 66 joints); and 20% improvement compared to baseline in 3 of the following 5 criteria, respectively: 1) Patient's global assessment of disease activity according to 100-mm VAS, 2) Physician's global assessment of disease activity according to 100-mm VAS, 3) participant's global assessment of pain according to 100-mm VAS, 4) Participant's assessment of functional ability via a Health Assessment Questionnaire-Disability Index (HAQ-DI), and 5) Acute phase reactant (ESR in mm/h or C-Reactive Protein \[CRP\] in milligrams per deciliter \[mg/dL\]).

Change From Week 24 in Bone Erosion Score at Week 40 for Participants in the Magnetic Resonance Imaging (MRI) SubstudyWeeks 24, Week 40

Bones from the wrist regions (carpal bones, distal radius, distal ulna, and metacarpal bases) and the metacarpophalangeal (MCP) joints (metacarpal heads and phalangeal bases) were assessed for erosion via MRI and scored separately based on the proportion of eroded bone compared to the 'assessed bone volume' judged from all available images. Scoring ranged from 0 (no erosion) to 10 (91-100%). Results were summed, resulting in scores from 0 to 80 for the wrist region, 0 to 150 for the MCP joints, and 0 to 230 on aggregate. A negative value for change from Week 24 in bone erosion score indicated an improvement.

Percentage of Participants Achieving 50% Improvement in American College of Rheumatology (ACR50) ResponseWeeks 24, 40, and 52

The ACR50 response at any time was defined as \>/=50% improvement compared to baseline in TJC (assessed on 68 joints) and SJC (assessed on 66 joints); and 50% improvement compared to baseline in 3 of the following 5 criteria, respectively: 1) Patient's global assessment of disease activity according to 100-mm VAS, 2) Physician's global assessment of disease activity according to 100-mm VAS, 3) participant's global assessment of pain according to 100-mm VAS, 4) Participant's assessment of functional ability via HAQ-DI, and 5) Acute phase reactant (ESR in mm/h or CRP in mg/dL).

Percentage of Participants With >/=1.2 Points Increase (Worsening) From Week 24 in DAS28 Score at Week 40 and 52Week 24, 40, and 52

The DAS28 was derived from assessments of ESR measured in mm/h, TJC28, SJC28, and Patient's global assessment of disease activity according to 100-mm VAS. DAS28 score was calculated as \[0.56 × square root of TJC\] + \[0.28 × square root of SJC\] + \[0.70 × natural log (ESR)\] + \[0.014 × VAS\]. DAS28- score could range from 0 to 10, where higher score represented higher disease activity.

Mean TCZ Serum ConcentrationBaseline, Weeks 12, 24, 36, 52 and follow up (Week 60)
Percentage of Participants With DAS28 Score <2.6 (DAS28 Remission)Week 40, Week 52

The DAS28 was derived from assessments of ESR measured in mm/h, TJC28, SJC28, and Patient's global assessment of disease activity according to 100-mm VAS. DAS28 score was calculated as \[0.56 × square root of TJC\] + \[0.28 × square root of SJC\] + \[0.70 × natural log (ESR)\] + \[0.014 × VAS\]. DAS28 score could range from 0 to 10, where higher score represented higher disease activity.

Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to TCZBaseline, Post-baseline (assessed at Weeks 12, 24, 36, 52 and at follow up [Week 60])

Percentage of participants with positive results for ATA against TCZ at Baseline and at any of the post-baseline assessment time-points was reported. Participants positive at any post-baseline time points were participants who had no positivity at baseline for the same assay.

Mean Soluble Interleukin-6 (IL-6) Receptor ConcentrationBaseline, Weeks 12, 24, 36, 52 and follow up (Week 60)

Trial Locations

Locations (154)

Phase Iii Clinical Research

🇺🇸

Fall River, Massachusetts, United States

Fort Smith Rheumatology, PC

🇺🇸

Fort Smith, Arkansas, United States

Joao Nascimento

🇺🇸

Bridgeport, Connecticut, United States

Precision Research Organization

🇺🇸

Miami Lakes, Florida, United States

Columbus Arthritis Center

🇺🇸

Columbus, Ohio, United States

University Hospitals Case Medical Center

🇺🇸

Cleveland, Ohio, United States

New England Medical Center; Dept. of Medicine, Div. of Rheumatology

🇺🇸

Boston, Massachusetts, United States

CHI St. Vincent Medical Group Hot Springs

🇺🇸

Hot Springs, Arkansas, United States

CV Mehta MD Medical Corp

🇺🇸

Hemet, California, United States

Arthritis & Osteoporosis Center Pc

🇺🇸

Hamden, Connecticut, United States

Denver Arthritis Clinic

🇺🇸

Denver, Colorado, United States

UMass Memorial Medical Center

🇺🇸

Worcester, Massachusetts, United States

Nisus Research/Northern Michigan Hospital

🇺🇸

Petoskey, Michigan, United States

Advanced Rheumatology, PC

🇺🇸

Lansing, Michigan, United States

St. Luke's Hospital Association of Duluth

🇺🇸

Duluth, Minnesota, United States

TriWest Research Associates, LLC

🇺🇸

El Cajon, California, United States

St. Paul Rheumatology

🇺🇸

Eagan, Minnesota, United States

Arthritis and Osteoporosis Associates of New Mexico

🇺🇸

Las Cruces, New Mexico, United States

The Center for Rheumatology

🇺🇸

Albany, New York, United States

Atlantic Coast Rheumatology

🇺🇸

Toms River, New Jersey, United States

St. Jude Hospital Yorba Linda DBA St. Joseph

🇺🇸

Fullerton, California, United States

Ocean Rheumatology

🇺🇸

Toms River, New Jersey, United States

Manhattan Medical Reserach

🇺🇸

New York, New York, United States

Shores Rheumatology

🇺🇸

Saint Clair Shores, Michigan, United States

Clinical Pharmacology Study Group

🇺🇸

Worcester, Massachusetts, United States

Clayton Medical Research

🇺🇸

Saint Louis, Missouri, United States

Clinical Research Center of Ct/Ny

🇺🇸

Danbury, Connecticut, United States

Manhasset Rheumatology

🇺🇸

Manhasset, New York, United States

Altoona Center For Clinical Research

🇺🇸

Duncansville, Pennsylvania, United States

Amarillo Center For Clinical Research

🇺🇸

Amarillo, Texas, United States

Rheumatology Research Group

🇺🇸

Lebanon, New Hampshire, United States

Arthritis & Osteoporosis Center

🇺🇸

Brooklyn, New York, United States

Buffalo Rheumatology Associates

🇺🇸

Orchard Park, New York, United States

St. Alexius Medical Center; Arthritis Clinic

🇺🇸

Bismarck, North Dakota, United States

Odyssey Research Services; Main Medical Building

🇺🇸

Bismarck, North Dakota, United States

Ramesh Gupta - PP

🇺🇸

Memphis, Tennessee, United States

Arthritis Associates

🇺🇸

Erie, Pennsylvania, United States

Arthritis and Osteoporosis Associates

🇺🇸

Manalapan, New Jersey, United States

Arthritis Care & Diagnostic Center

🇺🇸

Dallas, Texas, United States

Advanced Rheumatology & Arthritis Research Center

🇺🇸

Wexford, Pennsylvania, United States

Office of Premier Chatpar Md

🇺🇸

Plainview, New York, United States

Paramount Medical Research

🇺🇸

Middleburg Heights, Ohio, United States

Clinical Research Center of Reading

🇺🇸

Wyomissing, Pennsylvania, United States

Crystal Arthritis Center, Inc.

🇺🇸

Akron, Ohio, United States

Arthritis Group

🇺🇸

Philadelphia, Pennsylvania, United States

Adriana Pop-Moody MD Clinic PA

🇺🇸

Corpus Christi, Texas, United States

Ohio State University; Rheumatology; Immun/Rheum

🇺🇸

Columbus, Ohio, United States

Arthritis & Osteoporosis Clinic

🇺🇸

Waco, Texas, United States

C Michael Neuwelt MD Inc

🇺🇸

San Leandro, California, United States

Suncoast Research Group LLC

🇺🇸

Miami, Florida, United States

South Coast Research Center, Inc.

🇺🇸

Miami, Florida, United States

Indiana Uni Medical Center

🇺🇸

Indianapolis, Indiana, United States

Diagnostic Rheumatology & Research

🇺🇸

Indianapolis, Indiana, United States

G. T. Kelly, MD

🇺🇸

Las Vegas, Nevada, United States

Triangle Orthopaedics Associates, P.A.

🇺🇸

Durham, North Carolina, United States

Cincinnati Rheumatic Disease Study Group

🇺🇸

Cincinnati, Ohio, United States

Rheumatic Disease Clin Res Ctr

🇺🇸

Houston, Texas, United States

IntraFusion Researh Network

🇺🇸

Houston, Texas, United States

Accurate Clinical Research

🇺🇸

Houston, Texas, United States

NextGen Clinical Research Inc

🇺🇸

San Antonio, Texas, United States

Arthiritis & Osteoporosis Centre of South Texas

🇺🇸

San Antonio, Texas, United States

Uni Of Alabama,Birmingham; Medicine - Rheumatology

🇺🇸

Birmingham, Alabama, United States

Lynn Health Science Inst.

🇺🇸

Oklahoma City, Oklahoma, United States

Arthritis and Rheumatology; Center of Oklahoma PLLC

🇺🇸

Oklahoma City, Oklahoma, United States

Health Research of Oklahoma, Llc

🇺🇸

Oklahoma City, Oklahoma, United States

University of Colorado Hospital

🇺🇸

Aurora, Colorado, United States

McIlwain Medical Group

🇺🇸

Tampa, Florida, United States

Burnette & Silverfield, MDS

🇺🇸

Tampa, Florida, United States

Cape Fear Arthritis Care

🇺🇸

Leland, North Carolina, United States

Emkey Arthritis & Osteoporosis

🇺🇸

Wyomissing, Pennsylvania, United States

Pinnacle Research Group; Llc, Central

🇺🇸

Anniston, Alabama, United States

Clnical & Translational Reseach Center for Alabama, PC

🇺🇸

Tuscaloosa, Alabama, United States

Arizona Arthritis & Rheumatology Associates, P.C.

🇺🇸

Glendale, Arizona, United States

Arizona Arthritis & Rheumatology Research, Pllc

🇺🇸

Mesa, Arizona, United States

Rheumatology Associates of North Alabama

🇺🇸

Huntsville, Alabama, United States

Valley Arthritis Care

🇺🇸

Phoenix, Arizona, United States

Arizona Arthritis and Rheuma

🇺🇸

Mesa, Arizona, United States

Advanced Arthritis Care & Research

🇺🇸

Scottsdale, Arizona, United States

Little Rock Diagnostic Clinic

🇺🇸

Little Rock, Arkansas, United States

NEA Baptist Clinic

🇺🇸

Jonesboro, Arkansas, United States

Medvin Clinical Research

🇺🇸

Whittier, California, United States

San Diego Arthritis Med Clnc

🇺🇸

San Diego, California, United States

NRC Research Institute

🇺🇸

Orange, California, United States

Valerius Medical Group

🇺🇸

Los Alamitos, California, United States

Inland Rheumatology; Clinical Trials, Inc.

🇺🇸

Upland, California, United States

Arthritis Assoc & Osteoporosis; Ctr of Colorado Springs

🇺🇸

Colorado Springs, Colorado, United States

New England Research Associates

🇺🇸

Trumbull, Connecticut, United States

Arthritis & Rheumatism; Disease Specialities

🇺🇸

Aventura, Florida, United States

Rheumatolgy Consultants of Deleware

🇺🇸

Lewes, Delaware, United States

Javed Rheumatology Associates, Inc.

🇺🇸

Newark, Delaware, United States

Robert Levin, Md; Research Dept

🇺🇸

Dunedin, Florida, United States

Arthritis Rsrch of Florida, Inc.

🇺🇸

Palm Harbor, Florida, United States

Jeffrey Alper M.D Research

🇺🇸

Naples, Florida, United States

Arthritis Center Palm Harbor

🇺🇸

Palm Harbor, Florida, United States

West Broward Rheumatology Associates, Inc.

🇺🇸

Tamarac, Florida, United States

Pinellas Medical Research - Allegry & Rheumatology Associates, LLC

🇺🇸

Saint Petersburg, Florida, United States

Sarasota Arthritis Res Center

🇺🇸

Sarasota, Florida, United States

Advanced Clinical Research of Orlando, Inc.

🇺🇸

Winter Garden, Florida, United States

North Georgia Rheumatology

🇺🇸

Duluth, Georgia, United States

Arthritis Center of North Georgia

🇺🇸

Gainesville, Georgia, United States

North Georgia Rheumatology Group, PC

🇺🇸

Lawrenceville, Georgia, United States

Institute of Arthritis Research

🇺🇸

Idaho Falls, Idaho, United States

Springfield Clinic

🇺🇸

Springfield, Illinois, United States

Kansas City Internal Medicine

🇺🇸

Overland Park, Kansas, United States

Klein & Associates, M.D., P.A.

🇺🇸

Hagerstown, Maryland, United States

Arthritis & Diabetes Clinic, Inc

🇺🇸

Monroe, Louisiana, United States

Mansfield Medical Center

🇺🇸

Mansfield, Massachusetts, United States

Reliant Medical Group, Inc; Rheumatology

🇺🇸

Worcester, Massachusetts, United States

Fiechtner Research Inc

🇺🇸

Lansing, Michigan, United States

Arthritis and Osteoporosis; Treatment and Research Center

🇺🇸

Flowood, Mississippi, United States

Jackson Arthritis Clinic

🇺🇸

Flowood, Mississippi, United States

David S Rosenberg

🇺🇸

Florissant, Missouri, United States

Arthritis Consultants

🇺🇸

Saint Louis, Missouri, United States

Nashua Rheumatology - Foundation Medical Partners

🇺🇸

Nashua, New Hampshire, United States

Arthritis Rheumatic & Back Disease Associates

🇺🇸

Voorhees, New Jersey, United States

Cooper Cancer Institute

🇺🇸

Voorhees, New Jersey, United States

Rheumatology Associates of Long Island

🇺🇸

Smithtown, New York, United States

Arthritis Health Associates

🇺🇸

Syracuse, New York, United States

Carolina Bone & Joint P.A.

🇺🇸

Charlotte, North Carolina, United States

Asheville Arthritis & Osteoporosis Center, PA

🇺🇸

Asheville, North Carolina, United States

Medication Management

🇺🇸

Greensboro, North Carolina, United States

PMG Research of Hickory LLC

🇺🇸

Hickory, North Carolina, United States

Shanahan Rheumatology & Immunology, PLLC

🇺🇸

Raleigh, North Carolina, United States

STAT Research Inc

🇺🇸

Dayton, Ohio, United States

Clinical Research Source, Inc.

🇺🇸

Toledo, Ohio, United States

Arthritis Care Center Oklahoma

🇺🇸

Ardmore, Oklahoma, United States

Oklahoma Center For Arthritis Therapy & Research

🇺🇸

Tulsa, Oklahoma, United States

Healthcare Research Consultants

🇺🇸

Tulsa, Oklahoma, United States

Columbia Arthritis Center (Partnership Practice)

🇺🇸

Columbia, South Carolina, United States

Piedmont Arthritis Clinic

🇺🇸

Greenville, South Carolina, United States

West Tennessee Research Institute

🇺🇸

Jackson, Tennessee, United States

Diagnostic Group

🇺🇸

Beaumont, Texas, United States

AOCBV

🇺🇸

College Station, Texas, United States

Houston Inst. For Clinical Research

🇺🇸

Houston, Texas, United States

Metroplex Clinical Research

🇺🇸

Dallas, Texas, United States

Southwest Rheumatology

🇺🇸

Mesquite, Texas, United States

Accurate Clinical Management

🇺🇸

San Antonio, Texas, United States

Arthritis Clinic Of Central Texas

🇺🇸

San Marcos, Texas, United States

Crossroads Clinical Research, LLC

🇺🇸

Victoria, Texas, United States

South Puget Sound Clinical Research

🇺🇸

Olympia, Washington, United States

Wenatchee Valley Hospital & Clinics

🇺🇸

Wenatchee, Washington, United States

Rheumatic Disease Center

🇺🇸

Glendale, Wisconsin, United States

Arthritis Northwest, Spokane

🇺🇸

Spokane, Washington, United States

Mountain State Clinical Research

🇺🇸

Clarksburg, West Virginia, United States

Lakeshore Orthopedics

🇺🇸

Manitowoc, Wisconsin, United States

Gundersen Clinic Ltd;Sec. Rheumatology/Dept. of Internal Med

🇺🇸

Onalaska, Wisconsin, United States

Rheumatology Associates of Central Florida

🇺🇸

Orlando, Florida, United States

Arthritis and Rheumatology Clinic

🇺🇸

Orlando, Florida, United States

Clinical Research Consultants,LLC

🇺🇸

Kansas City, Missouri, United States

Low Country Rheumatology, PA

🇺🇸

Charleston, South Carolina, United States

Bluegrass Comm Research, Inc.

🇺🇸

Lexington, Kentucky, United States

Albuquerque Clinical Trials

🇺🇸

Albuquerque, New Mexico, United States

Austin Regional Clinic

🇺🇸

Austin, Texas, United States

Lovelace Scientific Resources Inc.

🇺🇸

Austin, Texas, United States

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