A Study to Evaluate the Efficacy and Safety of CC-220 in Subjects With Active Systemic Lupus Erythematosus

Phase 2

Completed

Conditions: Lupus Erythematosus, Systemic

Interventions: Other: Placebo
Drug: CC-220

Registration Number: NCT03161483

Lead Sponsor: Celgene

Brief Summary: The purpose of this Phase 2, multicenter, randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of an oral treatment regimen of CC-220 versus placebo in adult subjects with active systemic lupus erythematosus.

Approximately 280 subjects with a documented diagnosis of SLE will be randomized 2:2:1:2 to receive CC-220 (0.45 mg QD, 0.3 mg QD or 0.15 mg QD) or identically appearing placebo.

Detailed Description: The study consists of four phases:

* 4-week Screening Phase

* 24-week placebo-controlled phase Subjects will receive either 0.45 mg QD, 0.3 mg QD, 0.15 mg QD or placebo for the first 24 weeks of treatment.

* 28-week active treatment phase At Week 24, all subjects on placebo will be re-randomized to active treatment.

* 52-week long-term extension phase Subjects who complete the treatment phase may be eligible to roll over into a Long-term Extension of up to 52 weeks of treatment.

* 4 - 12-week observational follow-up All subjects who complete 52 weeks of treatment or discontinue the study early will enter a post-treatment observation follow-up phase. The Observational Follow-up Phase will consist of one visit 4 weeks following cessation of study drug for all subjects with an additional 12-week Observational Follow-up visit for males only.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 289

Inclusion Criteria

Male or female 18 years of age or older at the time of signing the informed consent.
Have a diagnosis of SLE for at least 6 months prior to the Screening Visit and fulfill the 1997 update of the 1982 American College of Rheumatology (ACR) Classification Criteria for SLE at the Screening Visit.
A SLEDAI 2K score of ≥ 6 points, WITH at least 4 points being a "clinical" SLEDAI 2K score. The "clinical" score excludes points attributable to any urine or blood laboratory results including immunologic measures.
At the Baseline Visit, a clinical SLEDAI 2K score of ≥ 4 points.
Have at least one of the following positive antibodies associated with SLE per the central laboratory within the Screening Phase:
- Positive antinuclear antibody (ANA) test at the central laboratory with a titer of 1:40 or greater, associated with a diagnosis of SLE,
- Anti-dsDNA antibodies elevated to above normal
- Anti-Smith (anti-Sm) antibody elevated to above normal
Females of childbearing potential must: Have two negative pregnancy tests as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment.

o Either commit to true abstinence from heterosexual contact or agree to use two forms of reliable contraception simultaneously.
Male subjects must: Practice true abstinence or agree to use a barrier contraception during sexual contact.

All subjects must:

Understand that the IP could have potential teratogenic risk.
Agree to abstain from donating blood while taking IP and for 28 days following discontinuation of the IP.
- Have been treated with at least one of the following SLE medications prior to the Screening Visit: antimalarials, immunosuppressants, and/or corticosteroids.
- Currently receiving stable doses of at least one of the following medications: systemic corticosteroids, antimalarials, and/or immunosuppressants.

Exclusion Criteria

Received intra-articular, intralesional, subcutaneous, intradermal, intramuscular or IV pulse corticosteroids 6 weeks prior to the Baseline Visit.
Received any other biologic or non-biologic immunosuppressive agent within 2 months of 5 pharmacokinetic half-lives (whichever is longer) prior to the Baseline Visit.
Have severe lupus nephritis defined as: estimated glomerular filtration rate of < 45 mL/1.73 m2 or proteinuria > 2000 mg/day based on protein to creatinine ratio, or active lupus nephritis that may require 'induction' therapy
Have active, severe or unstable neuropsychiatric lupus disease within 6 months of the Screening Visit.
Have serologic tests consistent with infection with either hepatitis B or hepatitis C, and/or confirmed history of hepatitis B or hepatitis C infection.
Have history of congenital and/or acquired immunodeficiencies (eg, common variable immunodeficiency, human immunodeficiency virus, etc).
Have active or history of recurrent bacterial, viral, fungal, mycobacterial or other infections, or any major episode of infection requiring hospitalization or treatment with intravenous or oral antibiotics within 4 weeks of the Screening Visit and at any time during the Screening Phase, up through the first dose of IP.
Have active tuberculosis or a history of latent or active tuberculosis
Have malignancy or history of malignancy, except for:
- treated (eg, cured) basal cell or squamous cell in situ skin carcinomas
- treated (eg, cured) cervical intraepithelial neoplasia Grade 1 and Grade 2
- treated (eg, cured) carcinoma in situ of the cervix with no evidence of recurrence within 5 years of the Screening Visit.
Have a diagnosis or history consistent with Antiphospholipid Syndrome or "triple antiphospholipid positivity" (ie, positive lupus anticoagulant, anticardiolipin, and anti-B2 glycoprotein).
Have history of arterial or venous thrombosis
Have history or current diagnosis of peripheral neuropathy (sensory or motor) ≥ Grade 2.
Have presence of active uveitis or any other ophthalmological finding that in the opinion of the Investigator is clinically significant.
Have other non-SLE driven inflammatory joint or skin disease or overlap syndromes as the primary disease.
Have clinically significant or unstable or uncontrolled acute or chronic disease not due to SLE
Does not meet required laboratory criteria.
Does not meet pre-specified periods for prohibited medications.
Pregnant or a breast-feeding female.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Weeks 0 to 24: CC-220 Placebo Controlled Phase: placebo once daily (QD)
CC-220 0.45 mg QD Placebo Controlled Phase	Placebo	* At Weeks 0 to 24: CC-220 Placebo Controlled Phase: CC-220 0.45 mg once daily (QD) * At Weeks 24 to 52: CC-220 Active Treatment Phase: CC-220 0.45 mg once daily (QD) * Long-term Extension Phase (52 weeks to 104 weeks): At Week 52 all subjects who elect to continue in the Long-term Extension will stay on the same dose they were on at the conclusion of the randomized, double-blind, active treatment phase.
C-220 0.3 mg QD Placebo Controlled Phase	CC-220	* At Weeks 0 to 24: CC-220 Placebo Controlled Phase: CC-220 0.3 mg once daily (QD) * At Weeks 24 to 52: CC-220 Active Treatment Phase: CC-220 0.30 mg once daily (QD) * Long-term Extension Phase (52 weeks to 104 weeks): At Week 52 all subjects who elect to continue in the Long-term Extension will stay on the same dose they were on at the conclusion of the randomized, double-blind, active treatment phase.
C-220 0.3 mg QD Placebo Controlled Phase	Placebo	* At Weeks 0 to 24: CC-220 Placebo Controlled Phase: CC-220 0.3 mg once daily (QD) * At Weeks 24 to 52: CC-220 Active Treatment Phase: CC-220 0.30 mg once daily (QD) * Long-term Extension Phase (52 weeks to 104 weeks): At Week 52 all subjects who elect to continue in the Long-term Extension will stay on the same dose they were on at the conclusion of the randomized, double-blind, active treatment phase.
CC-220 0.15 mg QD Placebo Controlled Phase	CC-220	* At Weeks 0 to 24: CC-220 Placebo Controlled Phase: CC-220 0.15 mg once daily (QD) * At Weeks 24 to 52: CC-220 Active Treatment Phase: CC-220 0.15 mg once daily (QD) * Long-term Extension Phase (52 weeks to 104 weeks): At Week 52 all subjects who elect to continue in the Long-term Extension will stay on the same dose they were on at the conclusion of the randomized, double-blind, active treatment phase.
CC-220 0.15 mg QD Placebo Controlled Phase	Placebo	* At Weeks 0 to 24: CC-220 Placebo Controlled Phase: CC-220 0.15 mg once daily (QD) * At Weeks 24 to 52: CC-220 Active Treatment Phase: CC-220 0.15 mg once daily (QD) * Long-term Extension Phase (52 weeks to 104 weeks): At Week 52 all subjects who elect to continue in the Long-term Extension will stay on the same dose they were on at the conclusion of the randomized, double-blind, active treatment phase.
CC-220 0.45 mg QD Placebo Controlled Phase	CC-220	* At Weeks 0 to 24: CC-220 Placebo Controlled Phase: CC-220 0.45 mg once daily (QD) * At Weeks 24 to 52: CC-220 Active Treatment Phase: CC-220 0.45 mg once daily (QD) * Long-term Extension Phase (52 weeks to 104 weeks): At Week 52 all subjects who elect to continue in the Long-term Extension will stay on the same dose they were on at the conclusion of the randomized, double-blind, active treatment phase.

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Achieve SLE Responder Index (SRI) (4) Response	Week 24	The primary objective is to evaluate the clinical efficacy of three doses of CC-220 (0.45 mg once per day \[QD\], 0.3 mg QD or 0.15 mg QD) compared to placebo, for the treatment of active systemic lupus erythematosus (SLE) using the SLE Responder Index at Week 24 Composite endpoint SRI(4), defined by the following criteria: - Reduction from Baseline of ≥ 4 points in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2K score and - No new one or more British Isles Lupus Assessment Group (BILAG) A or new (excludes A to B) 2 or more BILAG B items compared to Baseline using BILAG 2004 Index and - No worsening from Baseline defined by an increase of \< 0.30 points from Baseline on a Physician's Global Assessment (PGA) visual analog scale (VAS) from 0-3

Secondary Outcome Measures

Name	Time	Method
Mean Change From Baseline in Tender Joint Count in Participants With ≥ 2 Tender Joints at Baseline	Week 24	Joint tenderness and swelling will be noted as "present" or "absent," with no quantitation of severity using a 28- joint count. Note: Data presented is Adjusted mean data.
Number of Participants With SLEDAI 2K Score Improvement of ≥ 4 Points From Baseline	Week 24	The SLEDAI 2K score measures disease activity through assessment of 24 lupus manifestations using a weighted score of 1 to 8 points. A manifestation is recorded if it is present over the previous 30 days regardless of severity or whether it has improved or worsened. A SLEDAI 2K score of 3 to 4 points is representative of active disease and a decrease of 1 to 2 points is considered clinically meaningful.
Number of Participants With a ≥ 50% Reduction in Cutaneous Lupus Area and Severity Index (CLASI) Activity Score From Baseline, in Participants With Baseline CLASI Activity Score ≥ 10	Week 24	The CLASI Activity Score ranges from 0 to 70. To generate the activity score erythema is scored on a scale of 0 (absent) to 3 (dark red; purple/violaceous/crusted/hemorrhagic) and scale/hypertrophy are scored on a scale of 0 (absent) to 2 (verrucous/hypertrophic). Both the erythema and scale/hypertrophy scores are assessed in 13 different anatomical locations. In addition, the presence of mucous membrane lesions is scored on a scale of 0 (absent) to 1 (lesion or ulceration), the occurrence of recent hair loss is captured (1=yes; 0=no) and non-scarring alopecia is scored on a scale of 0 (absent) to 3 (focal or patchy in more than one quadrant). To calculate the activity score, all scores for erythema, scale/hypertrophy, mucous membrane lesions and alopecia are added together.
Number of Participants With no New Organ System Affected as Defined by 1 or More BILAG A or New (Excludes A to B) 2 or More BILAG B Items Compared to Baseline Using BILAG 2004 Index	Week 24	The BILAG 2004 is a composite index that is based on the Classic BILAG index. It is a clinical measure of lupus disease activity. This tool assesses the changing severity of clinical manifestations of SLE using an ordinal scale scoring system that contain 9 systems (constitutional, mucocutaneous, neuropsychiatric, musculoskeletal, cardiorespiratory, gastrointestinal, ophthalmic, renal and hematological). Activity in each organ system is scored as: A=most active disease; B=intermediate activity; C=mild, stable disease; D=previous involvement, currently inactive; E=no previous activity.
Percentage of Participants With no Worsening (Increase of < 0.30 Points From Baseline) in PGA Compared to Baseline	Week 24	The PGA uses a visual analog scale with scores between 0 and 3 to indicate worsening of disease. The scoring is as follows: 0 = none, 1 = mild disease, 2 = moderate disease, and 3 = severe disease.
Mean Change From Baseline in Swollen Joint Count in Participants With ≥ 2 Swollen Joints at Baseline	Week 24	Joint tenderness and swelling will be noted as "present" or "absent," with no quantitation of severity using a 28- joint count. Note: Data presented is Adjusted mean data.
Mean Change From Baseline in PGA Score	Week 24	The PGA uses a visual analog scale with scores between 0 and 3 to indicate worsening of disease. The scoring is as follows: 0 = none, 1 = mild disease, 2 = moderate disease, and 3 = severe disease.
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score	Week 24	The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The total FACIT-Fatigue score ranges from 0 to 52. Note: Data presented is Adjusted mean data.
Percentage of Participants With Corticosteroid Reduction	Week 24	- The percentage of participants with a prednisone or equivalent dose of ≥ 10 mg/day at Baseline whose prednisone or equivalent dose has been reduced to ≤ 7.5 mg/day by Week 16 and maintained through Week 24 with no flares between Week 16 and Week 24 - The percentage of participants with a prednisone or equivalent dose of ≥ 10 mg/day at Baseline whose prednisone or equivalent dose has been reduced to \< 10 mg/day by Week 16 and maintained through Week 24 with no flares between Week 16 and Week 24
Percent Change From Baseline in Corticosteroid Reduction	Week 24	Percent change from Baseline in oral corticosteroid (OCS) dose in subjects with prednisone or equivalent ≥ 10 mg/day at Baseline Note: Data presented is Adjusted mean data.
The Total Corticosteroid Dose From Baseline Through Week 24	Through Week 24	Standardized total oral corticosteroid (OCS) dose.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	from first dose to 28 days post-last dose through Week 24 (placebo-controlled phase), approximately 28 weeks total	Number of participants who experienced a TEAE during the course of the study

Trial Locations

Locations (184): North Shore-LIJ Health System-Division of Rheumatology
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Great Neck, New York, United States
University Of Pennsylvania
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Philadelphia, Pennsylvania, United States
Integral Rheumatology and Immunology Specialists
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Plantation, Florida, United States
Desert Medical Advances
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Palm Desert, California, United States
UCLA Division of Rheumatology
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Los Angeles, California, United States
Clinic of Robert Hozman
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Skokie, Illinois, United States
Advanced Rheumatology
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Lansing, Michigan, United States
Hershey Medical Center
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Hershey, Pennsylvania, United States
Centro Medico Privado de Reumatologia
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San Miguel de Tucumán, Argentina
Local Institution - 101
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Charlotte, North Carolina, United States
Local Institution - 630
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Quilmes, Argentina
Organización Médica de Investigación
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Buenos Aires, Argentina
Great Lakes Center of Rheumatology
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Lansing, Michigan, United States
Local Institution - 134
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Great Neck, New York, United States
Clinique de Rhumatologie Du Centre Du Quebec
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Quebec, Canada
CER Instituto Mèdico
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Quilmes, Argentina
Arthritis and Osteoporosis Associates of New Mexico
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Las Cruces, New Mexico, United States
Local Institution - 655
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Goiânia, Goiás, Brazil
Advanced Rheumatology & Arthritis Research Center, PC
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Wexford, Pennsylvania, United States
Local Institution - 676
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Bogota, Colombia
Local Institution - 628
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Buenos Aires, Argentina
Local Institution - 136
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Hershey, Pennsylvania, United States
Local Institution - 627
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San Miguel de Tucumán, Argentina
UT Southwestern Medical Center
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Dallas, Texas, United States
University of Pennsylvania Department of Dermatology
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Philadelphia, Pennsylvania, United States
Universitaire Ziekenhuizen (UZ) Leuven - Gasthuisberg
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Leuven, Belgium
Local Institution - 124
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Syracuse, New York, United States
Hospital General de Agudos Dr. Jose Maria Ramos Mejia
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Buenos Aires, Argentina
Local Institution - 425
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Brussels, Belgium
Local Institution - 426
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Liège, Belgium
Local Institution - 675
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Barranquilla, Colombia
Idearg S.A.S.
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Bogota, Colombia
SUNY Upstate Medical University
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Syracuse, New York, United States
Centro Internacional de Pesquisas
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Goiânia, Goiás, Brazil
Instituto de Investigaciones Clinicas de Quilmes
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Quilmes, Argentina
Local Institution - 326
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Paris, France
Centro de Investigacion en Reumatologia y Especialidades Medicas S.A.S. - Cireem S.A.S
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Bogota, Colombia
Azienda Ospedaliero - Universitaria di Cagliari
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Monserrato, Italy
Local Institution - 352
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Budapest, Hungary
Local Institution - 203
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Quebec, Canada
Local Institution - 506
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Kazan, Russian Federation
Leningrad Regional Clinical Hospital
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St. Petersburg, Russian Federation
Local Institution - 682
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Bogota, Colombia
Local Institution - 677
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Chia, Colombia
Local Institution - 503
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St. Petersburg, Russian Federation
Universitaetsklinikum Koeln
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Koeln, Germany
CHRU de Lille France
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Lille Cedex, France
Qualiclinic kft
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Budapest, Hungary
Medicity S.A.S.
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Bucaramanga, Colombia
Reumalab - Centro Integral de Reumatologia
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Medellin, Colombia
Local Institution - 507
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Moscow, Russian Federation
University of Ferrara, Azienda Ospedaliera-Universitaria S.Anna
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Ferrara, Italy
City Clinical Hospital
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Kazan, Russian Federation
Local Institution - 500
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Orenburg, Russian Federation
Servimed S.A.S.
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Bucaramanga, Colombia
Bekes Megyei Kozponti Korhaz
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Gyula, Hungary
Local Institution - 602
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Mexico, Distrito Federal, Mexico
ASST Spedali Civili P.O. di Brescia
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Brescia, Italy
CHU Hautepierre
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Strasbourg, France
Kemerovo State Medical Academy
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Kemerovo, Russian Federation
Hospital Pablo Tobon Uribe
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Medellin, Colombia
Local Institution - 376
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Koscian, Poland
Local Institution - 302
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Kiel, Germany
Assistance Publique - Hopitaux de Paris - Hopital Universitaire Pitie Salpetriere
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Paris, France
Centro Integral en Reumatología, S.A. de C.V.
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Guadalajara, Jalisco, Mexico
Local Institution - 505
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Kemerovo, Russian Federation
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
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Mainz, Germany
Egyesitett Szent Istvan es Szent Laszlo Korhaz - Rendelointezet
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Budapest, Hungary
Institute Niska Banja
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Niska Banja, Serbia
Local Institution - 479
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Niska Banja, Serbia
Local Institution - 400
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A Coruña, Spain
Local Institution - 480
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Kragujevac, Serbia
Hospital Universitario Vall D hebron
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Barcelona, Spain
Hospital Universitario Araba - Txagorritxu
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Vitoria-Gasteiz, Spain
Local Institution - 403
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Barcelona, Spain
Hospital Universitario de Canarias
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La Laguna, Spain
Local Institution - 405
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Santander, Spain
Local Institution - 350
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Budapest, Hungary
Emory University School of Medicine
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Atlanta, Georgia, United States
MetroHealth Medical Systems
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Cleveland, Ohio, United States
University of Pittsburgh UPMC Lupus Center of Excellence
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Pittsburgh, Pennsylvania, United States
Beth Israel Deaconness Medical Center
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Boston, Massachusetts, United States
Pioneer Research Solutions
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Houston, Texas, United States
Local Institution - 605
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Merida, Yucatán, Mexico
Unidad de Atencion Medica e Investigacion en Salud, S.C.
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Merida, Yucatán, Mexico
LMK Servicos Medicos S/S
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Porto Alegre, Rio Grande Do Sul, Brazil
Local Institution - 650
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Porto Alegre, Rio Grande Do Sul, Brazil
University of Miami
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Miami, Florida, United States
St. Anthony's Medical Center
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Oklahoma City, Oklahoma, United States
Local Institution - 204
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Winnipeg, Manitoba, Canada
Local Institution - 201
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Hamilton, Ontario, Canada
Local Institution - 200
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Quebec, Canada
Voronezh Regional Clinical Hopsital #1, Voronezh State Medical Academy
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Voronezh, Russian Federation
University of Colorado Denver
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Aurora, Colorado, United States
Bay Care Medical Group
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Tampa, Florida, United States
Local Institution - 626
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Cordoba, Argentina
Local Institution - 629
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Quilmes, Argentina
AZ Arthritis and Rheum Rsch, PLLC
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Mesa, Arizona, United States
Clinical and Translational Research Center of Alabama, PC
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Tuscaloosa, Alabama, United States
Saint Jude Heritage Medical Center
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Fullerton, California, United States
University of California San Diego Medical Center
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La Jolla, California, United States
Jefrey Lieberman, MD, PC
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Decatur, Georgia, United States
C Michael Neuwelt M D
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San Leandro, California, United States
Inland Rheumatology Clinical Trials
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Upland, California, United States
Centre For Rheumatology, Immun. And Arthritis
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Fort Lauderdale, Florida, United States
University of Maryland - School of Medicine
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Baltimore, Maryland, United States
Piedmont Hospital - Atlanta
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Atlanta, Georgia, United States
North Georgia Rheumatology
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Lawrenceville, Georgia, United States
DJL Clinical Research
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Charlotte, North Carolina, United States
NYU Langone Medical Center
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New York, New York, United States
Shanahan Rheumatology and Immunotherapy
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Raleigh, North Carolina, United States
Consultora Integral de Salud Centro Médico Privado
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Cordoba, Argentina
Virginia Mason Medical Center
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Seattle, Washington, United States
Local Institution - 625
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Buenos Aires, Argentina
Hospital Britanico de Buenos Aires
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Buenos Aires, Argentina
Hospital Privado Centro Medico de Cordoba
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Cordoba, Argentina
CHU de Liege
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Liège, Belgium
Hopital Erasme
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Brussels, Belgium
Local Institution - 427
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Leuven, Belgium
Centro de Estudos em Terapias Inovadoras LTDA
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Curitiba, Paraná, Brazil
Santa Casa de Misericórdia de Belo Horizonte
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Belo Horizonte, Brazil
Local Institution - 653
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Curitiba, Paraná, Brazil
Local Institution - 657
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Campinas, São Paulo, Brazil
State University of Campinas UNICAMP
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Campinas, São Paulo, Brazil
Local Institution - 652
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Belo Horizonte, Brazil
Local Institution - 651
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Rio de Janeiro, Brazil
Centro de Imunoterapia de Ipanema (CITIPA)
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Rio de Janeiro, Brazil
Hospital de Clinicas de Porto Alegre
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Porto Alegre, RS, Brazil
Local Institution - 205
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Calgary, Alberta, Canada
The University of Calgary
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Calgary, Alberta, Canada
University of Manitoba
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Winnipeg, Manitoba, Canada
Toronto Western Hospital
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Toronto, Ontario, Canada
Local Institution - 202
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Toronto, Ontario, Canada
CHUL du CHU de Quebec
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Quebec, Canada
Local Institution - 679
🇨🇴
Bucaramanga, Colombia
IPS Centro Integral de Reumatologia del Caribe Circaribe S.A.S.
🇨🇴
Barranquilla, Colombia
Local Institution - 678
🇨🇴
Medellin, Colombia
Preventive Care
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Chia, Colombia
Universitatsklinikum Schleswig-Holstein
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Kiel, Germany
Local Institution - 300
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Koeln, Germany
Centro de Investigacion en Artritis y Osteoporosis
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Mexicali, Baja California, Mexico
Local Institution - 610
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Mexicali, Baja California, Mexico
Local Institution - 600
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Guadalajara, Jalisco, Mexico
Hospital Angeles Lindavista
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D.f, Df, Mexico
Orenburg State Medical Academy
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Orenburg, Russian Federation
Institution of the Russian Academy of Medical Sciences Research Institute of Rheumatology of the Ru
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Moscow, Russian Federation
Saint Petersburg Research Institute for Emergency Medical Care
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St. Petersburg, Russian Federation
Local Institution - 502
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St. Petersburg, Russian Federation
State Higher Educational Institution
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St. Petersburg, Russian Federation
Local Institution - 504
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Vladimir, Russian Federation
Hospital Universitario a Coruna
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A Coruña, Spain
Hospital Marques de Valdecilla
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Santander, Spain
BioMed, LLC.
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Vladimir, Russian Federation
Local Institution - 377
🇵🇱
Bydgoszcz, Poland
Local Institution - 476
🇷🇸
Belgrade, Serbia
Local Institution - 608
🇲🇽
Mexico, Distrito Federal, Mexico
Local Institution - 606
🇲🇽
D.f, Df, Mexico
Biológicos Especializados S.A. de C.V.
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Mexico, Distrito Federal, Mexico
Samodzielny Publiczny Zespól Opieki Zdrowotnej w Koscianie Szpital im. Teodora Dunina
🇵🇱
Koscian, Poland
Clinica Integral de Osteoporosis y Artitis Reumatoide CLINOSAR
🇲🇽
Mexico, Distrito Federal, Mexico
Local Institution - 607
🇲🇽
Mexico, Distrito Federal, Mexico
Local Institution - 380
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Wroclaw, Woj. Dolnoslaskie, Poland
Samodzielny Publiczny Szpital Kliniczny nr 4, Klinika Reumatologii i Ukladowych Chorob Tkanki Laczne
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Lublin, Poland
Local Institution - 477
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Belgrade, Serbia
Local Institution - 478
🇷🇸
Belgrade, Serbia
Military Medical Academy
🇷🇸
Belgrade, Serbia
Clinical Center Kragujevac
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Kragujevac, Serbia
Local Institution - 680
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Medellin, Colombia
Local Institution - 351
🇭🇺
Gyula, Hungary
Centrum Medyczne Plejady
🇵🇱
Krakow, Poland
Local Institution - 475
🇷🇸
Belgrade, Serbia
Centro de Alta Especialidad en Reumatología e Investigación del Potosí S.C.
🇲🇽
San Luis Potosi, San Luis Potosí, Mexico
Centro de Investigación y Tratamiento Reumatológico
🇲🇽
Mexico, Distrito Federal, Mexico
Szpital Uniwersytecki nr 2 im. Dr Jana Biziela w Bydgoszczy
🇵🇱
Bydgoszcz, Poland
Local Institution - 375
🇵🇱
Krakow, Poland
Local Institution - 378
🇵🇱
Lublin, Poland
Niepubliczny Zaklad Opieki Zdrowotnej Biogenes Sp. z o.o.
🇵🇱
Wroclaw, Poland
Institute of Rheumatology Belgrade
🇷🇸
Belgrade, Serbia
Yale University School of Medicine
🇺🇸
New Haven, Connecticut, United States
University of Florida College of Medicine
🇺🇸
Gainesville, Florida, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
MAC Research Incorporated
🇨🇦
Hamilton, Ontario, Canada
Local Institution - 603
🇲🇽
San Luis Potosi, San Luis Potosí, Mexico
Montefiore Medical Center
🇺🇸
Bronx, New York, United States