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A Study to Assess the Efficacy and Safety of Abatacept in Adults With Active Primary Sjögrens Syndrome

Phase 3
Completed
Conditions
Sjogrens Disease
Interventions
Biological: Abatacept
Other: Placebo
Registration Number
NCT02915159
Lead Sponsor
Bristol-Myers Squibb
Brief Summary

The purpose of this study is to evaluate the efficacy of abatacept compared to placebo in patients with Sjögren's Syndrome.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
250
Inclusion Criteria
  • EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score of at least 5
  • Positive anti-SS-A/Ro antibody at screening
  • meet the 2016 American College of Rheumatology (ACR) / European League Against Rheumatism Classification Criteria for Sjögren's Syndrome (EULAR SS)
Read More
Exclusion Criteria
  • Secondary Sjögrens syndrome
  • Active life-threatening or organ-threatening complications of Sjögren's-syndrome
  • Other medical condition associated with sicca syndrome

Other protocol defined inclusion/exclusion criteria could apply

Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo for Abatacept for subcutaneous injection 125mg/mL in 1 mL pre-filled syringe for 6 months followed by Open-Label Abatacept for subcutaneous injection 125mg/mL in 1 mL pre-filled syringe for 6 months
AbataceptAbataceptAbatacept for subcutaneous injection 125mg/mL in 1 mL pre-filled syringe for 6 months followed by Open-Label Abatacept for subcutaneous injection 125mg/mL in 1 mL pre-filled syringe for 6 months
PlaceboAbataceptPlacebo for Abatacept for subcutaneous injection 125mg/mL in 1 mL pre-filled syringe for 6 months followed by Open-Label Abatacept for subcutaneous injection 125mg/mL in 1 mL pre-filled syringe for 6 months
Primary Outcome Measures
NameTimeMethod
Change From Baseline in EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI)Day 169

The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) total score is calculated as the sum of scores for activity level for each domain.

The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) Scoring Algorithm.

Domain: (Score) Constitutional: (No=0, Low=3, Moderate=6) Lymphadenopathy: (No=0, Low=4, Moderate=8, High=12) Glandular: (No=0, Low=2, Moderate=4) Articular: (No=0, Low=2, Moderate=4, High=6) Cutaneous: (No=0, Low=3, Moderate=6, High=9) Pulmonary: (No=0, Low=5, Moderate=10, High=15) Renal: (No=0, Low=5, Moderate=10, High=15) Muscular: (No=0, Low=6, Moderate=12, High=18) Peripheral Nervous System (PNS): (No=0, Low=5, Moderate=10, High=15) Central Nervous System (CNS): (No=0, Moderate=10, High=15) Haematological: (No=0, Low=2, Moderate=4, High=6) Biological: (No=0, Low=1, Moderate=2)

(No = No Disease Activity (DA), Low = Low DA, Moderate = Moderate DA, High = High DA)

Overall score, which can range from 0 to 123, a higher score indicates more disease activity

Secondary Outcome Measures
NameTimeMethod
Participants Who Achieve Minimally Clinically Important Change in ESSDAI in at Least 5 PointsDay 29, Day 57, Day 85, Day 113, Day 141, Day 169

Proportion of participants who achieve a minimally clinically important change (of at least 5 points) in the ESSDAI at all measured time points up to Day 169.

Change From Baseline in EULAR Sjogren's Syndrome Patient Reported Inde (ESSPRI)Day 169

The total score EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) is calculated as the mean of the 3 individual components.

Total Score Range (0 = Best outcome and 10 = Worst Outcome)

The scores for the ESSPRI individual components will be used as such reported by the participants and entered in the case report form (CRF), without any further calculations. It consists of 3 questions covering cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain. Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable), and overall score is calculated as the mean of 3 individual domains.

Change From Baseline in the Stimulated Whole Salivary FlowDay 169

The mean change from baseline in the stimulated whole salivary flow at Day 169

Change From Baseline in the Joint Component of DAS28-CRP: Tender Swollen Joints of at Least 3Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP.

Tender Joint: Count 1-28 Swollen Joint: Count 1-28

Negative Scores = Reduced number of joints impacted Positive Scores = Increased number of joints impacted

Change From Baseline in the CRP Component of DAS28-CRP: Tender Swollen Joint Count Less Than 3Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP.

CRP: measured lab value

Positive Number = Increased level of CRP Negative Number = Reduced Level of CRP

Change From Baseline in the CRP Component of DAS28-CRP: Tender Swollen Joints of at Least 3Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP.

CRP: measured lab value

Positive Number = Increased level of CRP Negative Number = Reduced Level of CRP

Change From Baseline in the Assessment of Disease Activity Component of DAS28-CRP: Tender Swollen Joints of at Least 3Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP.

Assesment of Disease Activity: 0-100 scale \[100=Most severe\]

Positive Numbers = Increased Disease Activity Negative Numbers = Decreased Diseased activity

Change From Baseline at All Measured Time Points in the ESSPRIDay 29, Day 57, Day 85, Day 113, Day 141, Day 169

The total score EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) is calculated as the mean of the 3 individual components.

Total Score Range (0 = Best outcome and 10 = Worst Outcome)

The scores for the ESSPRI individual components will be used as such reported by the participants and entered in the case report form (CRF), without any further calculations. It consists of 3 questions covering cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain. Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable), and overall score is calculated as the mean of 3 individual domains.

Change From Baseline in Components of ESSDAIDay 29, Day 57, Day 85, Day 113, Day 141 and Day 169

The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) total score is calculated as the sum of scores for activity level for each domain.

The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) Scoring Algorithm.

Domain: (Score for activity level) Constitutional: (No=0, Low=3, Moderate=6) Lymphadenopathy: (No=0, Low=4, Moderate=8, High=12) Glandular: (No=0, Low=2, Moderate=4) Articular: (No=0, Low=2, Moderate=4, High=6) Cutaneous: (No=0, Low=3, Moderate=6, High=9) Pulmonary: (No=0, Low=5, Moderate=10, High=15) Renal: (No=0, Low=5, Moderate=10, High=15) Muscular: (No=0, Low=6, Moderate=12, High=18) Peripheral Nervous System (PNS): (No=0, Low=5, Moderate=10, High=15) Central Nervous System (CNS): (No=0, Moderate=10, High=15) Haematological: (No=0, Low=2, Moderate=4, High=6) Biological: (No=0, Low=1, Moderate=2)

(No = No Disease Activity, Low = Low Disease Activity, Moderate = Moderate Disease Activity, High = High Disease Activity)

Change From Baseline in ESSPRI ComponentsDay 29, Day 57, Day 85, Day 113, Day 141, Day 169

The total score EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) is calculated as the mean of the 3 individual components.

Total Score Range (0 = Best outcome and 10 = Worst Outcome)

The scores for the ESSPRI individual components will be used as such reported by the participants and entered in the case report form (CRF), without any further calculations. It consists of 3 questions covering cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain. Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable), and overall score is calculated as the mean of 3 individual domains.

Change From Baseline of DAS28-C-reactive Peptide (CRP): In The Full PopulationDay 29, Day 57, Day 85, Day 113, Day 141, Day 169

The disease activity score DAS28-CRP is a continuous variable which is a composite of 4 variables: the 28 tender joint count (tender28), the 28 swollen joint count (swollen28), CRP and participant assessment of disease activity measure on a visual analogue scale (VAS) of 100mm.

DAS28-CRP = 0.56 \* sqrt(tender28) + 0.28 \* sqrt(swollen28) + 0.36 \* ln(hsCRP+1) + 0.014 \* VAS + 0.96.

(sqrt = Square root, ln = natural log)

Positive Scores = Increased Disease Activity Negative Scores = Reduced Disease Activity

Change From Baseline of DAS28-CRP: Tender Swollen Joint Count of at Least 3Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

The disease activity score DAS28-CRP is a continuous variable which is a composite of 4 variables: the 28 tender joint count (tender28), the 28 swollen joint count (swollen28), CRP and participant assessment of disease activity measure on a visual analogue scale (VAS) of 100mm.

DAS28-CRP = 0.56 \* sqrt(tender28) + 0.28 \* sqrt(swollen28) + 0.36 \* ln(hsCRP+1) + 0.014 \* VAS + 0.96.

(sqrt = Square root, ln = natural log)

Positive Scores = Increased Disease Activity Negative Scores = Reduced Disease Activity

Change From Baseline of DAS28-CRP: Tender Swollen Joints Count Less Than 3Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

The disease activity score DAS28-CRP is a continuous variable which is a composite of 4 variables: the 28 tender joint count (tender28), the 28 swollen joint count (swollen28), CRP and participant assessment of disease activity measure on a visual analogue scale (VAS) of 100mm.

DAS28-CRP = 0.56 \* sqrt(tender28) + 0.28 \* sqrt(swollen28) + 0.36 \* ln(hsCRP+1) + 0.014 \* VAS + 0.96.

(sqrt = Square root, ln = natural log)

Positive Scores = Increased Disease Activity Negative Scores = Reduced Disease Activity

Change From Baseline in the Joint Component of DAS28-CRP: In the Full PopulationDay 29, Day 57, Day 85, Day 113, Day 141, Day 169

The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP.

Tender Joint: Count 1-28 Swollen Joint: Count 1-28

Negative Scores = Reduced number of joints impacted Positive Scores = Increased number of joints impacted

Change From Baseline in the CRP Component of DAS28-CRP: In the Full PopulationDay 29, Day 57, Day 85, Day 113, Day 141, Day 169

The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP.

CRP: measured lab value

Positive Number = Increased level of CRP Negative Number = Reduced Level of CRP

Participants Who Achieve Minimally Clinically Important Change in ESSPRI in at Least 1 PointDay 29, Day 57, Day 85, Day 113, Day 141, Day 169

Proportion of participants who achieve a minimally clinically important change (of at least 1 point) in the ESSPRI at all measured time points up to Day 169.

Change From Baseline in Tear Break-up TimeDay 85, Day 169

The Mean change from baseline in Tear Break-up Time at all measured time points up to day 169

The CRF collects the time in seconds to first appearance of a random dry spot on the corneal surface for 3 repetitions in each eye. The average time will calculated for each eye averaging the 3 measurements for each eye separately. In case only 2 measurements are available, the average of the 2 measurements will be calculated. In case there is only 1 measurement, that measurement will be used for the analysis.

Change From Baseline in the Assessment of Disease Activity Component of DAS28-CRP: In the Full PopulationDay 29, Day 57, Day 85, Day 113, Day 141, Day 169

The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP.

Assesment of Disease Activity: 0-100 scale \[100=Most severe\]

Positive Numbers = Increased Disease Activity Negative Numbers = Decreased Diseased activity

Change From Baseline in the Joint Component of DAS28-CRP: Tender Swollen Joint Count Less Than 3Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP.

Tender Joint: Count 1-28 Swollen Joint: Count 1-28

Negative Scores = Reduced number of joints impacted Positive Scores = Increased number of joints impacted

Change From Baseline in the Assessment of Disease Activity Component of DAS28-CRP: Tender Swollen Joint Count Less Than 3Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP.

Assesment of Disease Activity: 0-100 scale \[100=Most severe\]

Positive Numbers = Increased Disease Activity Negative Numbers = Decreased Diseased activity

Change From Baseline in Schirmer's TestDay 85, Day 169

The Mean change from baseline in Schirmer's Test at all measured time points up to day 169

The length in millimeters that the strip wets during the 5 minute test period for each eye. Collection is done separately for each eye.

Laboratory Marked Abnormalities: Double Blind PeriodDay 1 up to first dose of OL abatacept or up to 56 post last dose in double -blind for those not in OL.

Laboratory values meeting the marked abnormality criteria

Participants Who Achieve Minimally Clinically Important Change in ESSDAI in at Least 3 PointsDay 29, Day 57, Day 85, Day 113, Day 141, Day 169

Proportion of participants who achieve a minimally clinically important change (of at least 3 points) in the ESSDAI at all measured time points up to Day 169.

Change From Baseline in Numeric Rating Scale for Eye DrynessDay 1, 29, 57, 85, 113, 141, 169

The mean change from baseline in patient symptoms using the Numeric Rating Scale (NRS) for eye dryness at all measured time points up to Day 169.

The oral and ocular dryness are each assessed by the patients with numeric rating scales from 0 to 10 with 0 representing no dryness and 10 representing maximal dryness

Change From Baseline in Physician Global Assessment of Disease ActivityDay 29, 57, 85, 113, 141, 169

The physician global assessment of disease activity are assessed with visual analog scales. The physician marks a vertical line through a horizontal line, where the beginning of the horizontal line represents the best situation, and the end of the horizontal line represents the very worst situation. The CRF collects the distance in millimeters from the start of the scale that is marked as well as the length of the scale in millimeters.

In cases that the length of the scale is in less or more than 100 millimeters, then the participants measurement will be rescaled to the equivalent of 100 millimeters using the formula below:

Rescale Measurement in mm = (measurement as reported on CRF in mm/length of the line on CRF in mm) \* 100mm

A negative score = physician assessment of disease activity has improved

A positive score = physician assessment of disease activity has worsened

Summary of Adverse Events: Double Blind PeriodDay 1 up to first dose of Open Label Treatment Period (OLTP) abatacept or up to 56 post last dose in double -blind for those not in OL.

Percentage of participants with adverse events, deaths, serious adverse events and adverse events leading to discontinuation

Change From Baseline at All Measured Time Points in the ESSDAIDay 29, Day 57, Day 85, Day 113, Day 141, Day 169

The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) total score is calculated as the sum of scores for activity level for each domain.

The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) Scoring Algorithm.

Domain: (Score) Constitutional: (No=0, Low=3, Moderate=6) Lymphadenopathy: (No=0, Low=4, Moderate=8, High=12) Glandular: (No=0, Low=2, Moderate=4) Articular: (No=0, Low=2, Moderate=4, High=6) Cutaneous: (No=0, Low=3, Moderate=6, High=9) Pulmonary: (No=0, Low=5, Moderate=10, High=15) Renal: (No=0, Low=5, Moderate=10, High=15) Muscular: (No=0, Low=6, Moderate=12, High=18) Peripheral Nervous System (PNS): (No=0, Low=5, Moderate=10, High=15) Central Nervous System (CNS): (No=0, Moderate=10, High=15) Haematological: (No=0, Low=2, Moderate=4, High=6) Biological: (No=0, Low=1, Moderate=2)

(No = No Disease Activity (DA), Low = Low DA, Moderate = Moderate DA, High = High DA)

Overall score, which can range from 0 to 123, a higher score indicates more disease activity

Change From Baseline in the Ocular Staining Score (OSS)Day 85, Day 169

The Mean change from baseline in OSS at all measured time points up to day 169

Score of 0 = No Staining Score of 12 = diffuse staining

The total score will be calculated as the sum of the score for these parameters for each eye.

Medial Nasal Bulbar Conjunctiva (MNBC) \[score scale: 0 - 3\], Corneal (CORN) Staining of Punctate Epithelial Erosions (PEE) \[score scale: 0 - 3\], Lateral Temporal Bulbar Conjunctiva (LTBC) \[score scale: 0 - 3\], Patches of Confluent Staining (CONF) \[score scale: 0 - 1\], PEE observed in the pupil region, i.e. central 4mm diameter portion of the cornea (PUPL) \[score scale: 0 - 1\], one of more filaments seen anywhere on the cornea (FILA) \[score scale: 0 - 1\]

Percentage of Participants With a Positive Antibody Response in the Cumulative Abatacept PeriodDay 365, post open label treatment day 85

Percentage of participants with at least one positive immunogenicity response On Day 365 (end of Open label treatment period) and day 85 post open label follow up period.

Laboratory Marked Abnormalities: Cumulative Abatacept PeriodDay 365 and 3 months of follow up approximately 450 Days

Laboratory values meeting the marked abnormality criteria

Change From Baseline in Unstimulated Salivary FlowDay 85, Day 169

The mean change from baseline in unstimulated whole salivary flow at all measured time points up to Day 169.

Change From Baseline in Stimulated Salivary FlowDay 85, Day 169

The mean change from baseline in Stimulated whole salivary flow at all measured time points up to Day 169.

Geometric Mean of Trough Concentration (Cmin) of AbataceptDay 29, 85, 113, 141, 169

Geometric mean of trough concentration (Cmin) of abatacept at all measured time points.

Summary of Adverse Events: Cumulative Abatacept PeriodDay 365 and 3 months of follow up approximately 450 Days

Percentage of participants with adverse events, deaths, serious adverse events and adverse events leading to discontinuation

Change From Baseline in Numeric Rating Scale for Mouth DrynessDay 1, 29, 57, 85, 113, 141, 169

The mean change from baseline in participant symptoms using the Numeric Rating Scale (NRS) for mouth dryness at all measured time points up to Day 169.

The oral and ocular dryness are each assessed by the patients with numeric rating scales from 0 to 10 with 0 representing no dryness and 10 representing maximal dryness

Change From Baseline in Participant Assessment of Disease ActivityDay 29, 57, 85, 113, 141, 169

The participant global assessment of disease activity are assessed with visual analog scales. The participant marks a vertical line through a horizontal line, where the beginning of the horizontal line represents the best situation, and the end of the horizontal line represents the very worst situation. The CRF collects the distance in millimeters from the start of the scale that is marked as well as the length of the scale in millimeters.

In cases that the length of the scale is in less or more than 100 millimeters, then the participants measurement will be rescaled to the equivalent of 100 millimeters using the formula below:

Rescale Measurement in mm = (measurement as reported on CRF in mm/length of the line on CRF in mm) \* 100mm

A negative score = participant assessment of disease activity has improved

A positive score = participant assessment of disease activity has worsened

Change From Baseline in Patient FatigueDay 29, 57, 85, 113, 141, 169

The mean change from baseline in patient fatigue using Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue assessment of disease activity at all measured time points up to Day 169.

PROMIS Fatigue instruments 10 Questions ranging from a score 0 to 40. Sum of the values gives you the raw sum. The raw is inputted into this formula to give you the raw score:

Raw Score = (Raw sum\*number of items on the short form)/(Number of items that were actually answered)

Raw score is translated to a T-Score using a table. T-Score is used as the final score.

The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. The standardized T-score is reported as the final score for each participant.

A negative T Score = Better Prognosis A positive T Score = Worse prognosis

Change From Baseline in Female Sexual Function Using the Female Sexual Function Index (FSFI)Day 85, Day 169

For the FSFI, is a 19 item instrument used for assessing key dimensions of female sexual function over the past 4 weeks with 6 domains being analyzed. The specific domains (desire, arousal, lubrication, orgasm, satisfaction, and pain) analyzed in the FSFI are scored on a scale ranging from 0 to 5, with higher scores indicating better performance. Domain scores are calculated by summing the scores of the individual questions that make up the domain and multiplying the sum by the factor in the table below. The full scale score is the sum of the six domain scores.

Full Scale Score range: 2.0(minimum score) - 36.0 (maximum score)

Negative Score = Reduced functioning Positive Score = Improved functioning

Change From Baseline in 36-item Short Form Health Survey (SF-36)Day 85, Day 169

The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health.

Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement

Percentage of Participants With a Positive Antibody ResponseDay 85 db, day 169 db, post treatment day 85

Percentage of participants with at least one positive immunogenicity response up to Day 169 and during 3 months follow up (for participants who discontinue during the 6-months double-blind).

Trial Locations

Locations (33)

Metroplex Clinical Research Center

🇺🇸

Dallas, Texas, United States

Ospedale Santa Maria Della Misericordia

🇮🇹

Udine, Italy

Local Institution

🇸🇪

Uppsala, Sweden

Instituto Reumatologico Strusberg

🇦🇷

Cordoba, Argentina

Medizinische Universitaetsklinik Freiburg

🇩🇪

Freiburg, Germany

St. Paul Rheumatology, P.A.

🇺🇸

Eagan, Minnesota, United States

Consultorios Medicos Dr. Catalan Pellet

🇦🇷

Caba, Argentina

West Tennessee Research Institute

🇺🇸

Jackson, Tennessee, United States

Krankenhaus St. Josef

🇩🇪

Wuppertal, Germany

Hopital Europeen

🇫🇷

Marseille, France

Scott Zashin Inc.

🇺🇸

Dallas, Texas, United States

Joint and Muscle Medical Care and Research Institute (JMMCRI)

🇺🇸

Charlotte, North Carolina, United States

Northwell Health

🇺🇸

Great Neck, New York, United States

Revmatologie s.r.o.

🇨🇿

Brno, Czechia

Duke Clinical Research Unit, Duke Univ Med Ctr, Duke South

🇺🇸

Durham, North Carolina, United States

Med Hochschule Hannover

🇩🇪

Hannover, Germany

University of Pittsburgh Medical Center

🇺🇸

Pittsburgh, Pennsylvania, United States

Hopital Lapeyronie

🇫🇷

Montpellier Cedex 5, France

Consultorio Medico de Reumatologia Dr.Jesus Alberto Lopez Garcia

🇲🇽

Leon, Guanajuato, Mexico

St. Jude Hospital Yorba Linda

🇺🇸

Fullerton, California, United States

Colorado Arthritis Associates

🇺🇸

Lakewood, Colorado, United States

Riverside Medical Clinic

🇺🇸

Riverside, California, United States

North Georgia Rheumatology Group

🇺🇸

Lawrenceville, Georgia, United States

Intermountain Research Center Inc.

🇺🇸

Boise, Idaho, United States

Johns Hopkins University

🇺🇸

Baltimore, Maryland, United States

Health Research Of Oklahoma

🇺🇸

Oklahoma City, Oklahoma, United States

Clinical Pharmacology Study Group

🇺🇸

Worcester, Massachusetts, United States

East Penn Rheumatology

🇺🇸

Bethlehem, Pennsylvania, United States

Altoona Center For Clinical Research

🇺🇸

Duncansville, Pennsylvania, United States

Instituto de Asistencia Reumatologica Integral

🇦🇷

San Fernando, Buenos Aires, Argentina

Organizacion Medica De Investigacion S.A. (Omi)

🇦🇷

Capital Federal, Buenos Aires, Argentina

Hospital Universitario Dr. Jose Eleuterio Gonzalez

🇲🇽

Monterrey, Nuevo LEON, Mexico

Centro de Alta Especialidad en Reumatologia e Investigacion del Potosi S.C.

🇲🇽

San Luis Potosi, Mexico

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