Study of KRYSTEXXA® (Pegloticase) Plus Methotrexate in Participants With Uncontrolled Gout

Phase 4

Completed

Conditions: Gout

Interventions: Biological: Pegloticase
Drug: methotrexate
Dietary Supplement: folic acid
Drug: placebo
Drug: gout flare prophylaxis regimen
Drug: fexofenadine
Drug: acetaminophen
Drug: methylprednisolone

Registration Number: NCT03994731

Lead Sponsor: Amgen

Brief Summary: The purpose of this study is to assess the potential for pegloticase with methotrexate (MTX) to increase the response rate seen with pegloticase alone, and to characterize the safety, tolerability and pharmacokinetics (PK) of the concomitant use of pegloticase with MTX, by comparing pegloticase co-administered with MTX to pegloticase co-administered with placebo for MTX in adults with uncontrolled gout.

Detailed Description: Study acquired from Horizon in 2024.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 152

Inclusion Criteria

Willing and able to give informed consent.
Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the study.
Adult men or women ≥18 years of age.
Uncontrolled gout, defined as meeting the following criteria:
- Hyperuricemia during the screening period defined as sUA ≥7 mg/dL, and;
- Failure to maintain normalization of sUA with xanthine oxidase inhibitors at the maximum medically appropriate dose, or with a contraindication to xanthine oxidase inhibitor therapy based on medical record review or subject interview, and;
- Symptoms of gout including at least 1 of the following:
  - Presence of at least one tophus
  - Recurrent flares defined as 2 or more flares in the past 12 months prior to screening
  - Presence of chronic gouty arthritis
Willing to discontinue any oral urate lowering therapy for at least 7 days prior to MTX dosing at Week -6 and remain off when receiving pegloticase infusions.
Women of childbearing potential (including those with an onset of menopause <2 years prior to screening, non-therapy-induced amenorrhea for <12 months prior to screening, or not surgically sterile [absence of ovaries and/or uterus]) must have negative serum/urine pregnancy tests during Screening and Week -6; subjects must agree to use 2 reliable forms of contraception during the study, one of which is recommended to be hormonal, such as an oral contraceptive. Hormonal contraception must be started ≥1 full cycle prior to Week -6 (start of MTX) and continue for 30 days after the last dose of pegloticase, or at least one ovulatory cycle after the last dose of MTX or placebo for MTX (whichever is the longest duration after the last dose of pegloticase or MTX or placebo for MTX). Highly effective contraceptive methods (with a failure rate <1% per year), when used consistently and correctly, include implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence, or vasectomized partner.
Men who are not vasectomized must agree to use appropriate contraception so as to not impregnate a female partner of reproductive potential during the study, beginning with the initiation of MTX at Week -6 and continuing and for at least 3 months after the last dose of MTX or placebo for MTX.
Able to tolerate MTX 15 mg orally for 2 weeks (Week -6 through Week -4) prior to randomization.

Exclusion Criteria

Weight >160 kg (352 pounds) at Screening.
Any serious acute bacterial infection, unless treated and completely resolved with antibiotics at least 2 weeks prior to the Week -6 Visit.
Severe chronic or recurrent bacterial infections, such as recurrent pneumonia or chronic bronchiectasis.
Current or chronic treatment with systemic immunosuppressive agents such as MTX, azathioprine, or mycophenolate mofetil; prednisone ≥10 mg/day or equivalent dose of other corticosteroid on a chronic basis (3 months or longer) would also meet exclusion criteria.
History of any transplant surgery requiring maintenance immunosuppressive therapy.
Known history of hepatitis B virus surface antigen positivity or hepatitis B DNA positivity.
Known history of hepatitis C virus ribonucleic acid (RNA) positivity.
Known history of Human Immunodeficiency Virus (HIV) positivity.
Glucose-6-phosphate dehydrogenase deficiency (tested at the Screening Visit).
Chronic renal impairment defined as estimated glomerular filtration rate (eGFR) < 40 mL/min/1.73 m^2 or currently on dialysis.
Non-compensated congestive heart failure or hospitalization for congestive heart failure within 3 months of the Screening Visit, uncontrolled arrhythmia, treatment for acute coronary syndrome (myocardial infarction or unstable angina), or uncontrolled blood pressure (>160/100 mmHg) prior to Randomization at Week -4.
Pregnant, planning to become pregnant, breastfeeding, planning to impregnate female partner, or not on an effective form of birth control, as determined by the Investigator.
Prior treatment with pegloticase, another recombinant uricase (rasburicase), or concomitant therapy with a polyethylene glycol-conjugated drug.
Known allergy to pegylated products or history of anaphylactic reaction to a recombinant protein or porcine product.
Contraindication to MTX treatment or MTX treatment considered inappropriate.
Known intolerance to MTX.
Receipt of an investigational drug within 4 weeks or 5 half-lives, whichever is longer, prior to MTX administration at Week -6 or plans to take an investigational drug during the study.
Liver transaminase levels (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) > upper limit of normal (ULN) or albumin < the lower limit of normal (LLN) at the Screening Visit).
Chronic liver disease.
White blood cell count < 4,000/µL, hematocrit < 32 percent, or platelet count < 75,000/µL.
Currently receiving systemic or radiologic treatment for ongoing cancer.
History of malignancy within 5 years other than non-melanoma skin cancer or in situ carcinoma of cervix.
Diagnosis of osteomyelitis.
Known history of hypoxanthine-guanine phosphoribosyl-transferase deficiency, such as Lesch-Nyhan and Kelley-Seegmiller syndrome.
Unsuitable candidate for the study, based on the opinion of the Investigator (e.g., cognitive impairment), such that participation might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements or complete the study.
Alcohol use in excess of 3 alcoholic beverages per week.
A known intolerance to all protocol standard gout flare prophylaxis regimens (i.e. subject must be able to tolerate at least one: colchicine and/or non-steroidal anti inflammatory drugs and/or low dose prednisone ≤10 mg/day).
Current pulmonary fibrosis, bronchiectasis or interstitial pneumonitis. If deemed necessary by the Investigator, a chest X-ray may be performed during Screening.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pegloticase + MTX	Pegloticase	Following the MTX Tolerability Assessment Period (Week -6 until the Week -4 visit, in which participants take oral MTX 15 mg weekly), participants tolerating MTX are randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period (from Week -4 to Day 1). During the Pegloticase + Immunomodulator (IMM) Period, in addition to oral 15 mg MTX, participants receive intravenous (IV) pegloticase 8 mg administered every 2 weeks (Q2W) for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants are also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for infusion reaction (IR) prophylaxis.
Pegloticase + MTX	folic acid	Following the MTX Tolerability Assessment Period (Week -6 until the Week -4 visit, in which participants take oral MTX 15 mg weekly), participants tolerating MTX are randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period (from Week -4 to Day 1). During the Pegloticase + Immunomodulator (IMM) Period, in addition to oral 15 mg MTX, participants receive intravenous (IV) pegloticase 8 mg administered every 2 weeks (Q2W) for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants are also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for infusion reaction (IR) prophylaxis.
Pegloticase + MTX	gout flare prophylaxis regimen	Following the MTX Tolerability Assessment Period (Week -6 until the Week -4 visit, in which participants take oral MTX 15 mg weekly), participants tolerating MTX are randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period (from Week -4 to Day 1). During the Pegloticase + Immunomodulator (IMM) Period, in addition to oral 15 mg MTX, participants receive intravenous (IV) pegloticase 8 mg administered every 2 weeks (Q2W) for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants are also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for infusion reaction (IR) prophylaxis.
Pegloticase + Placebo	Pegloticase	Following the MTX Tolerability Assessment Period (Week -6 until the Week -4 visit, in which participants take oral MTX 15 mg weekly), participants tolerating MTX are randomized to receive blinded oral placebo for MTX weekly during the Run-in Period (from Week -4 to Day 1). During the Pegloticase + IMM Period, in addition to oral placebo for MTX, all participants receive IV pegloticase 8 mg administered Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants are also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.
Pegloticase + Placebo	placebo	Following the MTX Tolerability Assessment Period (Week -6 until the Week -4 visit, in which participants take oral MTX 15 mg weekly), participants tolerating MTX are randomized to receive blinded oral placebo for MTX weekly during the Run-in Period (from Week -4 to Day 1). During the Pegloticase + IMM Period, in addition to oral placebo for MTX, all participants receive IV pegloticase 8 mg administered Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants are also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.
Pegloticase + Placebo	folic acid	Following the MTX Tolerability Assessment Period (Week -6 until the Week -4 visit, in which participants take oral MTX 15 mg weekly), participants tolerating MTX are randomized to receive blinded oral placebo for MTX weekly during the Run-in Period (from Week -4 to Day 1). During the Pegloticase + IMM Period, in addition to oral placebo for MTX, all participants receive IV pegloticase 8 mg administered Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants are also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.
Pegloticase + Placebo	gout flare prophylaxis regimen	Following the MTX Tolerability Assessment Period (Week -6 until the Week -4 visit, in which participants take oral MTX 15 mg weekly), participants tolerating MTX are randomized to receive blinded oral placebo for MTX weekly during the Run-in Period (from Week -4 to Day 1). During the Pegloticase + IMM Period, in addition to oral placebo for MTX, all participants receive IV pegloticase 8 mg administered Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants are also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.
Pegloticase + MTX	methotrexate	Following the MTX Tolerability Assessment Period (Week -6 until the Week -4 visit, in which participants take oral MTX 15 mg weekly), participants tolerating MTX are randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period (from Week -4 to Day 1). During the Pegloticase + Immunomodulator (IMM) Period, in addition to oral 15 mg MTX, participants receive intravenous (IV) pegloticase 8 mg administered every 2 weeks (Q2W) for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants are also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for infusion reaction (IR) prophylaxis.
Pegloticase + MTX	fexofenadine	Following the MTX Tolerability Assessment Period (Week -6 until the Week -4 visit, in which participants take oral MTX 15 mg weekly), participants tolerating MTX are randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period (from Week -4 to Day 1). During the Pegloticase + Immunomodulator (IMM) Period, in addition to oral 15 mg MTX, participants receive intravenous (IV) pegloticase 8 mg administered every 2 weeks (Q2W) for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants are also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for infusion reaction (IR) prophylaxis.
Pegloticase + MTX	acetaminophen	Following the MTX Tolerability Assessment Period (Week -6 until the Week -4 visit, in which participants take oral MTX 15 mg weekly), participants tolerating MTX are randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period (from Week -4 to Day 1). During the Pegloticase + Immunomodulator (IMM) Period, in addition to oral 15 mg MTX, participants receive intravenous (IV) pegloticase 8 mg administered every 2 weeks (Q2W) for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants are also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for infusion reaction (IR) prophylaxis.
Pegloticase + Placebo	methotrexate	Following the MTX Tolerability Assessment Period (Week -6 until the Week -4 visit, in which participants take oral MTX 15 mg weekly), participants tolerating MTX are randomized to receive blinded oral placebo for MTX weekly during the Run-in Period (from Week -4 to Day 1). During the Pegloticase + IMM Period, in addition to oral placebo for MTX, all participants receive IV pegloticase 8 mg administered Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants are also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.
Pegloticase + Placebo	acetaminophen	Following the MTX Tolerability Assessment Period (Week -6 until the Week -4 visit, in which participants take oral MTX 15 mg weekly), participants tolerating MTX are randomized to receive blinded oral placebo for MTX weekly during the Run-in Period (from Week -4 to Day 1). During the Pegloticase + IMM Period, in addition to oral placebo for MTX, all participants receive IV pegloticase 8 mg administered Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants are also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.
Pegloticase + Placebo	fexofenadine	Following the MTX Tolerability Assessment Period (Week -6 until the Week -4 visit, in which participants take oral MTX 15 mg weekly), participants tolerating MTX are randomized to receive blinded oral placebo for MTX weekly during the Run-in Period (from Week -4 to Day 1). During the Pegloticase + IMM Period, in addition to oral placebo for MTX, all participants receive IV pegloticase 8 mg administered Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants are also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.
Pegloticase + MTX	methylprednisolone	Following the MTX Tolerability Assessment Period (Week -6 until the Week -4 visit, in which participants take oral MTX 15 mg weekly), participants tolerating MTX are randomized to receive blinded oral MTX 15 mg weekly during the Run-in Period (from Week -4 to Day 1). During the Pegloticase + Immunomodulator (IMM) Period, in addition to oral 15 mg MTX, participants receive intravenous (IV) pegloticase 8 mg administered every 2 weeks (Q2W) for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants are also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for infusion reaction (IR) prophylaxis.
Pegloticase + Placebo	methylprednisolone	Following the MTX Tolerability Assessment Period (Week -6 until the Week -4 visit, in which participants take oral MTX 15 mg weekly), participants tolerating MTX are randomized to receive blinded oral placebo for MTX weekly during the Run-in Period (from Week -4 to Day 1). During the Pegloticase + IMM Period, in addition to oral placebo for MTX, all participants receive IV pegloticase 8 mg administered Q2W for a total of 26 infusions from Day 1 through the Week 50 Visit. Per protocol, participants are also required to take folic acid, at least one protocol standard gout flare prophylaxis regimen (i.e. colchicine and/or nonsteroidal anti-inflammatory drugs and/or low-dose prednisone ≤10 mg/day), and a regimen of fexofenadine, acetaminophen, and methylprednisolone for IR prophylaxis.

Primary Outcome Measures

Name	Time	Method
Percentage of Serum Uric Acid (sUA) Responders (sUA < 6 mg/dL) During Month 6	Month 6 (Weeks 20, 21, 22, 23 and 24)	Responders are defined as participants achieving and maintaining sUA \< 6 mg/dL for at least 80% of the time during Month 6. Month 6 includes pre- and post-infusion sUA assessments at Weeks 20 and 22, non-infusion sUA at Weeks 21 and 23, pre-infusion sUA at Week 24 and any unscheduled sUA between Week 20 and Week 24. A participant must have had ≥ 2 sUA observations from different visits in order to be eligible as a responder. Participants meeting the stopping rule (those with a pre-infusion sUA \>6 mg/dL at 2 consecutive scheduled trial visits beginning with the Week 2 Visit stopped pegloticase dosing) were counted as non-responders.

Secondary Outcome Measures

Name	Time	Method
Mean Change From Baseline HAQ Pain Score at Week 52	Baseline, Week 52	The HAQ-Pain score rates the participant's pain over the past week from 0 to 100 with 0 = no pain and 100 = severe pain. A change from baseline value of 0 is imputed at the first post-baseline visit for any participants without post-baseline values.
Mean Change From Baseline in HAQ Health Score at Week 52	Baseline, Week 52	The HAQ health scale is a self-reported measure of overall health. Participants are asked to rate how they are doing, considering all the ways arthritis affects them, on a scale of 0 to 100, where 0 represents very well and 100 represents very poor. A change from baseline value of 0 is imputed at the first post-baseline visit for any participants without post-baseline values.
Percentage of sUA (sUA < 6 mg/dL) Responders During Month 12	Month 12 (Weeks 48, 50 and 52)	Responders are defined as participants achieving and maintaining sUA \<6 mg/dL for at least 80% of the time during Month 12 (Weeks 48, 50 and 52). Month 12 includes pre- and post-infusion sUA Weeks 48 and 50, pre-infusion sUA at Week 52, and any unscheduled sUA assessments done at unscheduled visits between Week 48 and 52. A participant must have had ≥ 2 sUA observations from different visits in order to be eligible as a responder. Participants meeting the stopping rule (those with a pre-infusion sUA \>6 mg/dL at 2 consecutive scheduled trial visits beginning with the Week 2 Visit stopped pegloticase dosing) were counted as non-responders.
Percentage of Participants With Complete Resolution of ≥ 1 Tophi at Week 52	Baseline, Week 52	Percentage of participants with complete resolution of ≥ 1 tophi (using digital photography) at Week 52 in participants with tophi at baseline. Participants with resolution of ≥ 1 tophi at a visit are participants with resolution of ≥ 1 tophi at the visit (i.e. have complete response), and no progressive disease for any other tophi.
Mean Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 52	Baseline, Week 52	HAQ-DI is a self-report functional status instrument that is filled out by the participant and measures disability over the past week via 20 questions relating to 8 domains of function: dressing, grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. The HAQ-DI ranges from 0 to 3 with higher values indicating higher disability. A change from baseline value of 0 is imputed at the first post-baseline visit for any participants without post-baseline values.

Trial Locations

Locations (60): Arizona Arthritis and Rheumatology Research, PLLC-East
🇺🇸
Mesa, Arizona, United States
Axis Clinical Trials
🇺🇸
Los Angeles, California, United States
Prohealth Research Center
🇺🇸
Doral, Florida, United States
MD Medical Research
🇺🇸
Oxon Hill, Maryland, United States
Benefis Hospital
🇺🇸
Great Falls, Montana, United States
Buffalo Rheumatology and Medicine
🇺🇸
Orchard Park, New York, United States
Medication Management, LLC
🇺🇸
Greensboro, North Carolina, United States
Diagnostic and Interventional Nephrology Of Houston
🇺🇸
Houston, Texas, United States
Research Consultants - Frostwood
🇺🇸
Houston, Texas, United States
Research Consultants - Astoria
🇺🇸
Houston, Texas, United States
Applied Research Center of Arkansas, Inc
🇺🇸
Little Rock, Arkansas, United States
Arizona Arthritis and Rheumatology Research, PLLC - Flagstaff
🇺🇸
Flagstaff, Arizona, United States
Arizona Arthritis and Rheumatology Research, PLLC-West
🇺🇸
Glendale, Arizona, United States
St. Luke's Clinic - Rheumatology
🇺🇸
Meridian, Idaho, United States
Physician Research Collaboration, LLC
🇺🇸
Lincoln, Nebraska, United States
University of Alabama
🇺🇸
Birmingham, Alabama, United States
TriWest Research Associates
🇺🇸
El Cajon, California, United States
Advanced Investigative Medicine, Inc.
🇺🇸
Hawthorne, California, United States
ClinEdge Sierra Rheumatology, Inc.
🇺🇸
Roseville, California, United States
ACRC Studies
🇺🇸
Poway, California, United States
San Fernando Valley Health Institute
🇺🇸
Van Nuys, California, United States
East Bay Rheumatology Medical Group, Inc.
🇺🇸
San Leandro, California, United States
Medvin Clinical Research
🇺🇸
Tujunga, California, United States
Ventura Clinical Trials
🇺🇸
Ventura, California, United States
University of Colorado Division of Rheumatology
🇺🇸
Aurora, Colorado, United States
Denver Arthritis Clinic
🇺🇸
Denver, Colorado, United States
Avail Clinical Research
🇺🇸
DeLand, Florida, United States
Omega Research Maitland
🇺🇸
Orlando, Florida, United States
DMI Research
🇺🇸
Pinellas Park, Florida, United States
Napa Research Center
🇺🇸
Pompano Beach, Florida, United States
GCP Clinical Research
🇺🇸
Tampa, Florida, United States
Florida Medical Clinic, LLC
🇺🇸
Zephyrhills, Florida, United States
The Center for Rheumatology and Bone Research
🇺🇸
Wheaton, Maryland, United States
Infusion Associates
🇺🇸
Grand Rapids, Michigan, United States
Clinical Research Institute of Michigan, LLC
🇺🇸
Saint Clair Shores, Michigan, United States
Long Island Arthritis & Osteoporosis Care
🇺🇸
Babylon, New York, United States
Santa Fe Rheumatology
🇺🇸
Santa Fe, New Mexico, United States
NorthEast Rheumatology
🇺🇸
Concord, North Carolina, United States
ClinEdge PMG Research of Hickory, LLC
🇺🇸
Hickory, North Carolina, United States
NorthEast Rheumatology/Atrium Health
🇺🇸
Concord, North Carolina, United States
PMG Research of Wilmington, LLC
🇺🇸
Wilmington, North Carolina, United States
Shelby Clinical Research, LLC
🇺🇸
Shelby, North Carolina, United States
ClinEdge PMG Research of Salisbury, LLC
🇺🇸
Salisbury, North Carolina, United States
Premier Clinical/STAT Research
🇺🇸
Dayton, Ohio, United States
Paramount Medical Research & Consulting, LLC
🇺🇸
Middleburg Heights, Ohio, United States
Clinical Research Source Inc.
🇺🇸
Perrysburg, Ohio, United States
Premier Clinical/STAT Research - Springboro
🇺🇸
Springboro, Ohio, United States
Piedmont Arthritis Clinic
🇺🇸
Greenville, South Carolina, United States
Altoona Center for Clinical Research
🇺🇸
Duncansville, Pennsylvania, United States
Articularis Healthcare Group
🇺🇸
Summerville, South Carolina, United States
West Tennessee Research Institute
🇺🇸
Jackson, Tennessee, United States
Ramesh C. Gupta, M.D.
🇺🇸
Memphis, Tennessee, United States
Arthritis Clinic of Central Texas
🇺🇸
San Marcos, Texas, United States
Arthritis & Osteoporosis Clinic - Waco
🇺🇸
Waco, Texas, United States
Clear Lake Specialties
🇺🇸
Webster, Texas, United States
Western Washington Arthritis Clinic
🇺🇸
Bothell, Washington, United States
Rheumatic Disease Center
🇺🇸
Glendale, Wisconsin, United States
Arthritis Northwest
🇺🇸
Spokane, Washington, United States
Providence St. John's Health Clinic
🇺🇸
Santa Monica, California, United States
Orthopedic Physicians Alaska
🇺🇸
Anchorage, Alaska, United States