MedPath

A Study to Evaluate the Efficacy and Safety of Dapirolizumab Pegol in Study Participants With Moderately to Severely Active Systemic Lupus Erythematosus

Phase 3
Completed
Conditions
Systemic Lupus Erythematosus
Interventions
Other: Placebo
Drug: DZP
Registration Number
NCT04294667
Lead Sponsor
UCB Biopharma SRL
Brief Summary

The purpose of this study is to evaluate the ability of dapirolizumab pegol (DZP) as an add-on treatment to standard of care (SOC) medication to achieve clinically relevant long term improvement of moderate to severe disease activity.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
321
Inclusion Criteria
  • Rescreening will be allowed once during the study in case there is new evidence for an inclusion criterion that was not fulfilled at the first screening or in case a study participant no longer meets an exclusion criterion or screening period exceeded the maximum duration due to delays in screening processes

  • Study participant must be ≥16 years of age, unless restricted by local regulation, at the time of signing the Informed Consent form (ICF)

  • Study participants who have moderate to severe disease activity due to either persisting active SLE or due to an acute worsening of SLE in the scope of frequent flaring/relapsing-remitting systemic lupus erythematosus (SLE) despite stable standard of care (SOC) medication defined as:

    a. Diagnosed with SLE at least 24 weeks before the Screening Visit (Visit 1) study entry by a qualified physician b. Classified by 2019 SLE European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for SLE c. With serological evidence for SLE at Screening as demonstrated by at least 1 of the following: i) Evidence for anti-dsDNA (in central laboratory at Screening) ii) Either complement C3 < lower limit of normal (LLN) OR complement C4 <LLN OR elevated erythrocyte-bound complement C4d (where available) as measured by central laboratory iii) Antinuclear antibodies with a titer of at least 1:80 confirmed by central laboratory in combination with evidence of at least 1 of the following SLE typical autoantibodies:

    1. Anti-Smith (anti-Sm) antibodies (central laboratory) 2. Anti-Sjögren's syndrome antibody A (Anti-SSA) (Ro)/Anti-Sjögren's syndrome antibody B (anti-SSB) (La) autoantibodies (central laboratory) 3. Historic evidence for anti-dsDNA antibodies

    d. Moderately to severely active defined as

  • British Isles Lupus Assessment Group Disease Activity Index 2004 (BILAG 2004) Grade B in ≥2 organ systems and/or a BILAG 2004 Grade A in ≥1 organ systems at Screening and Baseline Visit AND

  • Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) ≥6 at Screening Visit AND

  • SLEDAI-2K without labs ≥4 at Baseline Visit

    e. Receiving the following SOC medication at stable dose:

    • Antimalarial treatment in combination with corticosteroids and/or immunosuppressants or as stand-alone treatment if justified OR Treatment with corticosteroids and/or immunosuppressants if anti-malarial treatment is not possible
Exclusion Criteria
  • Study participant has any medical or psychiatric condition (including conditions due to neuropsychiatric systemic lupus erythematosus (SLE)) that, in the opinion of the Investigator, could jeopardize or would compromise the study participant's ability to participate in this study. This includes study participants with a life threatening condition
  • Study participant has a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins, or monoclonal antibodies
  • Study participant has a history of malignancy, except the following treated cancers: cervical carcinoma in situ, basal cell carcinoma, or dermatological squamous cell carcinoma
  • Study participant has an increased risk for thromboembolic events due to an ongoing heart disease or due to a medical device, including but not limited to vascular graft, valvular heart disease, atrial fibrillation, or a heart rhythm disorder
  • Study participant has evidence of human immunodeficiency virus (HIV) infection, agammaglobulinemias, T-cell deficiencies, or human T-cell lymphotropic virus-1 infection
  • Study participant had a reactivated latent infection (example, cytomegalovirus, herpes simplex virus, or herpes zoster infection) or opportunistic infection (including but not limited to, pneumocystis, cytomegalovirus, or severe herpes zoster infection) within 12 weeks prior to the first study medication infusion (Visit 2), or is currently receiving suppressive therapy for an opportunistic infection
  • Study participants who have received live/live attenuated vaccines within 6 weeks prior to the first study medication infusion
  • Study participant has clinically significant active or latent infection
  • Study participant has a mixed connective tissue disease, scleroderma, and/or overlap syndrome of these diseases with SLE
  • Study participant takes any protocol defined prohibited concomitant medication
  • Study participant has previously been randomized within this study or participant has previously been assigned to treatment with dapirolizumab pegol (DZP) in a study evaluating DZP
  • Study participant has participated in another study of an IMP within the previous 12 weeks or 5 half-lives of the investigational medicinal product (IMP) whatever is longer or is currently participating in another study of an IMP
  • Study participant has chronic kidney failure stage 4, manifested by estimated glomerular filtration rate <30mL/min/1.73m^2, or serum creatinine >2.5 mg/dL, or participant has proteinuria >3 g/day, or protein: creatinine ratio >340 mg/mmol at the Screening Visit

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboSubjects will receive placebo througout the Treatment Period.
Dapirolizumab pegolDZPSubjects will receive dapriolizumab pegol througout the Treatment Period.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With Achievement of BILAG 2004-based Composite Lupus Assessment (BICLA) Response at Week 48Week 48

Study participants were considered to be a BILAG 2004-based Composite Lupus Assessment (BICLA) responder if all of the following were fulfilled:

* British Isles Lupus Assessment Group Disease Activity Index 2004 (BILAG 2004) improvement without worsening (A scores at Baseline improved to B, C or D; B scores improved to C or D; no new A scores and less than or equal to \[≤\] 1 new B.); Here, score A ("Active"): Severely active disease; score B ("Beware"): Moderately active disease; score C ("Contentment"): Mild stable disease; score D ("Discount"): Inactive now but previously active; and

* No worsening in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score compared to Baseline Visit (defined as no increase in SLEDAI-2K total score); and

* No worsening in the Physician's Global Assessment of Disease (PGA) compared to Baseline Visit defined as \[≤\] 10 millimeter (mm) increase on a 100 mm visual analog scale (VAS).

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With Achievement of BICLA Response at Week 24Week 24

Study participants were considered to be a BICLA responder if all of the following were fulfilled:

* BILAG 2004 improvement without worsening (A scores at Baseline improved to B, C or D; B scores improved to C or D; no new A scores and ≤ 1 new B.); Here, score A ("Active"): Severely active disease; score B ("Beware"): Moderately active disease; score C ("Contentment"): Mild stable disease; score D ("Discount"): Inactive now but previously active; and

* No worsening in the SLEDAI-2K total score compared to Baseline Visit (defined as no increase in SLEDAI-2K total score); and

* No worsening in the PGA compared to Baseline Visit defined as ≤ 10 mm increase on a 100 mm VAS.

Percentage of Participants With Achievement of BICLA Response at Week 12Week 12

Study participants were considered to be a BICLA responder if all of the following were fulfilled:

* BILAG 2004 improvement without worsening (A scores at Baseline improved to B, C or D; B scores improved to C or D; no new A scores and ≤ 1 new B.); Here, score A ("Active"): Severely active disease; score B ("Beware"): Moderately active disease; score C ("Contentment"): Mild stable disease; score D ("Discount"): Inactive now but previously active and

* No worsening in the SLEDAI-2K total score compared to Baseline Visit (defined as no increase in SLEDAI-2K total score); and

* No worsening in the PGA compared to Baseline Visit defined as ≤ 10 mm increase on a 100 mm VAS.

Percentage of Participants With Achievement of Prevention of Severe British Isles Lupus Assessment Group (BILAG) Flares (Severe BILAG Flare-free) Through Week 48During Treatment Period up to Week 48

A severe BILAG flare was defined as a british isles lupus assessment group disease activity index 2004 (BILAG 2004) Grade A in any system due to individual items that were new or worse qualifying for the Grade A. Determination of items that were new or worse and were qualifying for the Grade A were according to the supplementary information for the numerical scoring of the BILAG-2004 index. Here, Grade A ("Active"): Severely active disease (sufficient to require systemic immunosuppressant or anticoagulant therapy.

Percentage of Participants With Achievement of Lupus Low Disease Activity State (LLDAS) in ≥50% of Post-Baseline Visits Through Week 48During Treatment Period up to Week 48

The LLDAS includes domains that capture the absence of organ-threatening disease activity and harmful treatment burden. The LLDAS is defined as:

* SLEDAI-2K score was ≤4 with no activity in major organ systems.

* No new and/or worsening disease activity defined as no SLEDAI-2K component documented as present that was not documented present at the previous visit.

* PGA ≤ 33 mm.

* Prednisone equivalent systemic dose for systemic lupus erythematosus (SLE) indication ≤ 7.5 mg per day.

* Stable standard maintenance doses of immunosuppressive drugs as allowed by protocol, defined as no increase in dose in the past 12 weeks and no dose higher than allowed as per protocol.

Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) at Week 48From Baseline (Day 1) to Week 48

The SLEDAI-2K is a global index which includes 24 clinical and laboratory variables such as antibodies, renal, and hematological components measured 30 days before, and at the timepoint of assessment. The variables were weighted by the type of manifestation, but not by severity or dynamic of the individual item. The SLEDAI-2K includes scoring for antibodies (anti-dsDNA positive or negative) and low complement, as well as some renal and hematologic parameters. The total score falls between 0 and 105, with higher scores representing increased disease activity. Mixed effects models for repeated measurements (MMRM).

Percentage of Participants With Achievement of BILAG Improvement Without Worsening at Week 48Week 48

The BILAG improvement without worsening defined as A scores at Baseline improved to B, C or D; B scores improved to C or D; no new A scores and ≤1 new B Score. Here, score A ("Active"): Severely active disease (sufficient to require systemic immunosuppressant or anticoagulant therapy; score B ("Beware"): Moderately active disease (requires low dose or local immunosuppressant therapy or symptomatic therapy; score C ("Contentment"): Mild stable disease (no indication for changes in treatment); score D ("Discount"): Inactive now but previously active.

Change From Baseline in Physician's Global Assessment (PGA) at Week 48From Baseline (Day 1) to Week 48

The PGA is a measure of systemic lupus erythematosus (SLE) signs and symptoms by the physician using a visual analog scale of 0 to 100mm, Where 0 indicate "very good", asymptomatic, and no limitation of normal activity and 100 indicate "severe disease".

Percentage of Participants With Achievement of Systemic Lupus Erythematosus Responder Index Response - 4 (SRI-4) Response at Week 48Week 48

The SRI-4 define responders as meeting all of the following criteria:

* Reduction in SLEDAI-2K score of ≥ 4.

* No shift from BILAG 2004 Grade B, C, D, or E to A post-Baseline. Here, Grade A ("Active"): Severely active disease; Grade B ("Beware"): Moderately active disease; Grade C ("Contentment"): Mild stable disease; Grade D ("Discount"): Inactive now but previously active; Grade E ("Excluded"): Never affected.

* No more than 1 shift from BILAG 2004 Grade C, D, or E to B post-Baseline.

* No worsening in the PGA compared to study entry defined as ≤ 10 mm increase on a 100 mm visual analog scale, equivalent to less than a 10 mm increase in the PGA compared to study entry score.

Percentage of Participants With Achievement of Prevention of Moderate/Severe BILAG Flares (Moderate/Severe BILAG Flare-free) Through Week 48During Treatment Period up to Week 48

Achievement of prevention of moderate/severe BILAG flares through Week 48 was defined as the percentage of participants with no moderate or severe flare through Week 48. A severe BILAG flare was defined as a BILAG 2004 Grade A in any system due to individual items that were new or worse qualifying for the Grade A. Determination of items that were new or worse and were qualifying for the Grade A, according to the supplementary information for the numerical scoring of the BILAG-2004 index. A moderate BILAG flare was defined as 2 or more BILAG 2004 Grade B due to individual items that were new or worse and were qualifying for the Grade B in any system. Determination of items that were new or worse qualifying for the Grade B, according to the supplementary information for the numerical scoring of the BILAG- 2004 index. Here, Grade A ("Active"): Severely active disease; Grade B ("Beware"): Moderately active disease.

Time to Severe BILAG Flare Through Week 48During Treatment Period up to Week 48

Time to severe BILAG flare (the event) through Week 48 was defined as the time from randomization until the start of the event. A severe BILAG flare was defined as a BILAG 2004 Grade A in any system due to individual items that were new or worse qualifying for the Grade A. Determination of items that were new or worse and were qualifying for the Grade A, according to the supplementary information for the numerical scoring of the BILAG-2004 index. Here, Grade A ("Active"): Severely active disease.

Time to Moderate/Severe BILAG Flare Through Week 48During Treatment Period up to Week 48

Time to moderate/severe BILAG flare (the event) through Week 48 was defined as the time from randomization until the start of the event. Moderate BILAG flare was defined as 2 or more BILAG 2004 Grade B due to individual items that were new or worse and were qualifying for the Grade B in any system. Determination of items that were new or worse qualifying for the Grade B, according to the supplementary information for the numerical scoring of the BILAG-2004 index. Severe BILAG flare was defined as a BILAG 2004 Grade A in any system due to individual items that were new or worse qualifying for the Grade A. Determination of items that were new or worse and are qualifying for the Grade A, according to the supplementary information for the numerical scoring of the BILAG-2004 index. Here, Grade A ("Active"): Severely active disease; Grade B ("Beware"): Moderately active disease.

Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) During the StudyFrom Baseline (Day 1) until Safety Follow-Up (up to Week 54)

An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of investigational medicinal product (IMP), whether or not considered related to the IMP. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IMP. Treatment-emergent AEs were those with onset date on or after the first administration of study drug, and up to 60 days after last dose.

Percentage of Participants With Serious Treatment-emergent Adverse Events During the StudyFrom Baseline (Day 1) until Safety Follow-Up (up to Week 54)

A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: Results in death; Is life-threatening, Requires in patient hospitalization or prolongation of existing hospitalization; Results in persistent disability/incapacity; Is a congenital anomaly/birth defect; and Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above. Treatment-emergent AEs were those with onset date on or after the first administration of study drug, and up to 60 days after last dose.

Percentage of Participants With Treatment-emergent Adverse Events of Special Interest During the StudyFrom Baseline (Day 1) until Safety Follow-Up (up to Week 54)

An adverse event of special interest (AESIs) is any AE that a regulatory authority has mandated be reported on an expedited basis, regardless of the seriousness, expectedness, or relatedness of the AE to the administration of a product/compound.

Percentage of Participants With Treatment-emergent Adverse Events of Special Monitoring During the StudyFrom Baseline (Day 1) until Safety Follow-Up (up to Week 54)

An AE of special monitoring is a product-specific AEs, adverse reactions, or safety topics considered as requiring special monitoring by UCB.

Trial Locations

Locations (177)

Sl0043 50418

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Colleyville, Texas, United States

Sl0043 40380

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Sofia, Bulgaria

Sl0043 50257

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La Jolla, California, United States

Sl0043 50383

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Beverly Hills, California, United States

Sl0043 50378

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Loma Linda, California, United States

Sl0043 50258

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Los Angeles, California, United States

Sl0043 50340

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Orange, California, United States

Sl0043 50331

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Poway, California, United States

Sl0043 50239

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Brandon, Florida, United States

Sl0043 50059

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Ormond Beach, Florida, United States

Sl0043 50324

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Plantation, Florida, United States

Sl0043 50240

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Idaho Falls, Idaho, United States

Sl0043 50382

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Atlanta, Georgia, United States

Sl0043 50368

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Atlanta, Georgia, United States

Sl0043 50360

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Skokie, Illinois, United States

Sl0043 50474

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Hopkinsville, Kentucky, United States

Sl0043 50288

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Cumberland, Maryland, United States

Sl0043 50015

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Hagerstown, Maryland, United States

Sl0043 50333

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Grand Blanc, Michigan, United States

Sl0043 50366

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Canton, New York, United States

Sl0043 50010

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Brooklyn, New York, United States

Sl0043 50334

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New York, New York, United States

Sl0043 50266

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Great Neck, New York, United States

Sl0043 50264

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Manhasset, New York, United States

Sl0043 50077

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New York, New York, United States

Sl0043 50238

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Charlotte, North Carolina, United States

Sl0043 50241

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Syracuse, New York, United States

Sl0043 50364

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Philadelphia, Pennsylvania, United States

Sl0043 50147

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Hershey, Pennsylvania, United States

Sl0043 50020

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Duncansville, Pennsylvania, United States

Sl0043 50001

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Jackson, Tennessee, United States

Sl0043 50263

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Amarillo, Texas, United States

Sl0043 50338

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Bellaire, Texas, United States

Sl0043 50057

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Dallas, Texas, United States

Sl0043 50036

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Mesquite, Texas, United States

Sl0043 50304

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Dallas, Texas, United States

Sl0043 50050

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Beckley, West Virginia, United States

Sl0043 50061

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Spokane, Washington, United States

Sl0043 60002

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Capital Federal, Argentina

Sl0043 60001

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Ciudad Autonoma de Buenos Aire, Argentina

Sl0043 60029

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Mendoza, Argentina

Sl0043 60011

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San Juan, Argentina

Sl0043 60003

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Quilmes, Argentina

Sl0043 30020

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Parkville, Australia

Sl0043 30025

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St Albans, Australia

Sl0043 40387

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Wien, Austria

Sl0043 40123

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Bruxelles, Belgium

Sl0043 40189

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Plovdiv, Bulgaria

Sl0043 40522

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Plovdiv, Bulgaria

Sl0043 50374

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Calgary, Canada

Sl0043 50337

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Edmonton, Canada

Sl0043 50259

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Rimouski, Canada

Sl0043 50045

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Toronto, Canada

Sl0043 50044

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Trois-rivieres, Canada

Sl0043 60021

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Providencia, Santiago, Chile

Sl0043 60013

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Barranquilla, Colombia

Sl0043 60030

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Santiago, Chile

Sl0043 60019

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Barranquilla, Colombia

Sl0043 40066

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Praha 2, Czechia

Sl0043 40505

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Paris Cedex 12, France

Sl0043 40386

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Cologne, Germany

Sl0043 40506

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Montpellier Cedex 5, France

Sl0043 40322

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Dessau, Germany

Sl0043 40356

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Dresden, Germany

Sl0043 40072

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Freiburg, Germany

Sl0043 40024

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Hanover, Germany

Sl0043 40027

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Herne, Germany

Sl0043 40378

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Athens, Greece

Sl0043 40078

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Leipzig, Germany

Sl0043 40402

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Tübingen, Germany

Sl0043 40377

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Crete, Greece

Sl0043 40507

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Larisa, Greece

Sl0043 40375

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Thessaloniki, Greece

Sl0043 40413

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Gyula, Hungary

Sl0043 40031

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Szeged, Hungary

Sl0043 20141

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Busan, Korea, Republic of

Sl0043 20106

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Daejeon, Korea, Republic of

Sl0043 20108

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Incheon, Korea, Republic of

Sl0043 20104

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Seoul, Korea, Republic of

Sl0043 50317

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Chihuahua, Mexico

Sl0043 50250

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Cuernavaca, Mexico

Sl0043 50249

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Guadalajara, Mexico

Sl0043 50271

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Leon, Mexico

Sl0043 50252

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Merida, Mexico

Sl0043 50251

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Monterrey, Mexico

Sl0043 60026

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Arequipa, Peru

Sl0043 60008

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Lima, Peru

Sl0043 40490

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Krakow, Poland

Sl0043 40502

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Krakow, Poland

Sl0043 40037

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Lublin, Poland

Sl0043 40151

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Lublin, Poland

Sl0043 40483

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Nadarzyn, Poland

Sl0043 40044

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Poznan, Poland

Sl0043 40090

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Poznan, Poland

Sl0043 40097

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Warszawa, Poland

Sl0043 40394

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Warszawa, Poland

Sl0043 40382

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Galati, Romania

Sl0043 40383

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Bucuresti, Romania

Sl0043 40466

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Kragujevac, Serbia

Sl0043 40045

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A Coruna, Spain

Sl0043 40160

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Barcelona, Spain

Sl0043 40101

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Sabadell, Spain

Sl0043 40341

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Málaga, Spain

Sl0043 40521

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Mérida, Spain

Sl0043 40400

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Sevilla, Spain

Sl0043 20142

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Taichung City, Taiwan

Sl0043 40099

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Vigo, Spain

Sl0043 20113

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Taichung City, Taiwan

Sl0043 20099

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Taipei City, Taiwan

Sl0043 20082

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Taoyuan City, Taiwan

Sl0043 50321

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Morgantown, West Virginia, United States

Sl0043 40006

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Plovdiv, Bulgaria

Sl0043 60015

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Santiago de Chile, Chile

Sl0043 60007

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Chia, Colombia

Sl0043 50328

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Tucson, Arizona, United States

Sl0043 50341

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Washington, District of Columbia, United States

Sl0043 50285

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Lake Charles, Louisiana, United States

Sl0043 60022

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Quilmes, Argentina

Sl0043 60006

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Bogota, Colombia

Sl0043 60016

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Bucaramanga, Colombia

Sl0043 40501

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Haidari - Athens, Greece

Sl0043 40499

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Szekesfehervar, Hungary

Sl0043 50273

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Las Vegas, Nevada, United States

Sl0043 60014

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Tucuman, Argentina

Sl0043 60028

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Medellín, Colombia

Sl0043 40411

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Debrecen, Hungary

Sl0043 20182

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Davao, Philippines

Sl0043 40388

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Graz, Austria

Sl0043 40060

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Liege, Belgium

Sl0043 40482

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Bialystok, Poland

Sl0043 40392

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Novi Sad, Serbia

Sl0043 60018

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Santiago, Chile

Sl0043 60027

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Bogota, Colombia

Sl0043 20111

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Manila, Philippines

Sl0043 40098

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Warszawa, Poland

Sl0043 40397

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Wroclaw, Poland

Sl0043 60031

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Monteria, Colombia

Sl0043 60023

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Lima, Peru

Sl0043 20110

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Angeles, Philippines

Sl0043 20181

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Makati, Philippines

Sl0043 40481

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Wroclaw, Poland

Sl0043 40464

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Bucharest, Romania

Sl0043 40461

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Belgrade, Serbia

Sl0043 40412

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Budapest, Hungary

Sl0043 20095

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Taipei, Taiwan

Sl0043 60009

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Lima, Peru

Sl0043 40119

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Bydgoszcz, Poland

Sl0043 40398

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Katowice, Poland

Sl0043 40393

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Belgrade, Serbia

Sl0043 40489

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Odense, Denmark

Sl0043 40084

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Catania, Italy

Sl0043 40472

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Ferrara, Italy

Sl0043 40514

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Genova, Italy

Sl0043 40291

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Milano, Italy

Sl0043 40448

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Milano, Italy

Sl0043 40471

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Milano, Italy

Sl0043 40509

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Padova, Italy

Sl0043 40492

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Rozzano, Italy

Sl0043 40148

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Roma, Italy

Sl0043 50140

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Birmingham, Alabama, United States

Sl0043 50052

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Phoenix, Arizona, United States

Sl0043 50122

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Miami, Florida, United States

Sl0043 50275

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La Palma, California, United States

Sl0043 50377

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San Diego, California, United States

Sl0043 50219

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Detroit, Michigan, United States

Sl0043 50330

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Cincinnati, Ohio, United States

Sl0043 50316

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San Leandro, California, United States

Sl0043 50339

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Denver, Colorado, United States

Sl0043 50310

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Chicago, Illinois, United States

Sl0043 50262

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Oklahoma City, Oklahoma, United States

Sl0043 50365

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Pittsburgh, Pennsylvania, United States

Sl0043 50267

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Seattle, Washington, United States

Sl0043 50283

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Tampa, Florida, United States

Sl0043 50329

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Tampa, Florida, United States

Sl0043 50367

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New Haven, Connecticut, United States

Sl0043 50362

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Gainesville, Florida, United States

Sl0043 50179

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Winston-Salem, North Carolina, United States

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