A Study of the Safety and Effectiveness of Lyophilized Certolizumab Pegol in the Treatment of Signs and Symptoms of Rheumatoid Arthritis and in Prevention of Joint Damage in Patients With Active Rheumatoid Arthritis

Phase 3

Completed

Conditions: Rheumatoid Arthritis

Interventions: Biological: Certolizumab Pegol

Registration Number: NCT00175877

Lead Sponsor: UCB Pharma

Brief Summary: An open ended study in which patients who completed the double-blind study CDP870-027 \[NCT00152386\] are given Certolizumab Pegol (CZP) and assessed for signs and symptoms of Rheumatoid Arthritis (RA).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 857

Inclusion Criteria

Patients must have either failed to achieve American College of Rheumatology 20 % Response Criteria (ACR20) at Weeks 12 and 14 in C87027 [NCT00152386], or must have completed the entire Week 52 assessment of C87027 [NCT00152386] trial.

Exclusion Criteria

A diagnosis of any other inflammatory Arthritis (e.g. Psoriatic Arthritis or Ankylosing Spondylitis)
A secondary, non-inflammatory type of Arthritis (e.g. Osteoarthritis or Fibromyalgia) that in the Investigator's opinion is symptomatic enough to interfere with evaluation of the effect of CDP870 on the patient's primary diagnosis of Rheumatoid Arthritis
Any concomitant biological therapy
Any experimental therapy, within or outside a clinical trial

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Certolizumab Pegol	Certolizumab Pegol	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection.

Primary Outcome Measures

Name	Time	Method
Percentage of Subjects With at Least One Adverse Event (AE) From First Certolizumab Pegol (CZP) Dose up to Approximately 7 Years	From first dose of CZP to the end of the open-label study (approximately 7 years)	An AE is any untoward medical occurrence in a subject or trial subject that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage. First dose of Certolizumab Pegol (CZP) was at Baseline of the preceding double-blind study \[NCT00152386\] for subjects randomized to CZP, or at Entry Visit (Week 0) of this study for subjects randomized to Placebo.
Percentage of Subjects With at Least One Serious Adverse Event (SAE) From First Certolizumab Pegol (CZP) Dose up to Approximately 7 Years	From first dose of CZP to the end of the open-label study (approximately 7 years)	A SAE is any untoward medical occurrence that at any dose: * Results in death * Is life-threatening * Requires in patient hospitalisation or prolongation of existing hospitalisation * Results in persistent or significant disability/incapacity, or * Is a congenital anomaly or birth defect * Is as infection that requires treatment parenteral antibiotics * Other important medical events which based on medical or scientific judgement may jeopardise the patients, or may require medical or surgical intervention to prevent any of the above First dose of CZP was at Baseline of the preceding double-blind study \[NCT00152386\] for subjects randomized to CZP, or at Entry Visit (Week 0) of this study for subjects randomized to Placebo.
Percentage of Subjects Who Withdrew Due to an Adverse Event (AE) During the Study	From Entry Visit (Week 0) to the end of the study (approximately 6.5 years)	An AE is any untoward medical occurrence in a subject or trial subject that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage. The results of this Primary Outcome Measure are summarized from the Adverse Event pages of the Case Report Forms.

Secondary Outcome Measures

Name	Time	Method
Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 96	From Baseline of the preceding double-blind study to Week 96 of the open-label study	The assessments are based on a 20 % or greater improvement from Baseline to Week 96 in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 144	From Baseline of the preceding double-blind study to Week 144 of the open-label study	The assessments are based on a 20 % or greater improvement from Baseline to Week 144 in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 192	From Baseline of the preceding double-blind study to Week 192 of the open-label study	The assessments are based on a 20 % or greater improvement from Baseline to Week 192 in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 240	From Baseline of the preceding double-blind study to Week 240 of the open-label study	The assessments are based on a 20 % or greater improvement from Baseline to Week 240 in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Completion/Withdrawal	From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)	The assessments are based on a 20 % or greater improvement from Baseline to Completion/Withdrawal in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 48	From Baseline of the preceding double-blind study to Week 48 of the open-label study	The assessments are based on a 50 % or greater improvement from Baseline to Week 48 in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 48	From Baseline of the preceding double-blind study to Week 48 of the open-label study	The assessments are based on a 20 % or greater improvement from Baseline to Week 48 in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 96	From Baseline of the preceding double-blind study to Week 96 of the open-label study	The assessments are based on a 50 % or greater improvement from Baseline to Week 96 in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 144	From Baseline of the preceding double-blind study to Week 144 of the open-label study	The assessments are based on a 50 % or greater improvement from Baseline to Week 144 in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 192	From Baseline of the preceding double-blind study to Week 192 of the open-label study	The assessments are based on a 50 % or greater improvement from Baseline to Week 192 in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 240	From Baseline of the preceding double-blind study to Week 240 of the open-label study	The assessments are based on a 50 % or greater improvement from Baseline to Week 240 in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Completion/Withdrawal	From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)	The assessments are based on a 50 % or greater improvement from Baseline to Completion/Withdrawal in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 48	From Baseline of the preceding double-blind study to Week 48 of the open-label study	The assessments are based on a 70 % or greater improvement from Baseline to Week 48 in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 96	From Baseline of the preceding double-blind study to Week 96 of the open-label study	The assessments are based on a 70 % or greater improvement from Baseline to Week 96 in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 144	From Baseline of the preceding double-blind study to Week 144 of the open-label study	The assessments are based on a 70 % or greater improvement from Baseline to Week 144 in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 192	From Baseline of the preceding double-blind study to Week 192 of the open-label study	The assessments are based on a 70 % or greater improvement from Baseline to Week 192 in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 240	From Baseline of the preceding double-blind study to Week 240 of the open-label study	The assessments are based on a 70 % or greater improvement from Baseline to Week 240 in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Completion/Withdrawal	From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)	The assessments are based on a 70 % or greater improvement from Baseline to Completion/Withdrawal in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Change From Baseline of the Preceding Double-Blind Study to Week 96 in Modified Total Sharp Score (mTSS)	From Baseline of the preceding double-blind study to Week 96 of the open-label study	The mTSS quantifies the extent of bone erosions and joint space narrowing for 44 and 42 joints, respectively, as assessed by x-rays of the hands and feet. The score ranges from 0 to 448 with higher scores representing greater damage. A negative value in mTSS change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.
Change From Baseline of the Preceding Double-Blind Study to Completion/Withdrawal Visit in Health Assessment Questionnaire - Disability Index (HAQ-DI) Total Score	From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)	The HAQ-DI assesses the degree of difficulty experienced in eight domains (Dressing and Grooming, Arising, Eating, Walking, Hygiene, Reach, Gripping, Other Activities) of daily living activities using 20 questions. The HAQ-DI is calculated by summing the domain scores and dividing them by the number of domains. It ranges from 0 (no difficulty) to 3 (unable to do). Negative values indicate an improvement from Baseline to the Post-Baseline Visit with larger negative values showing a better improvement.
Change From Baseline to Completion/Withdrawal Visit in Duration of Morning Stiffness	From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)	Morning stiffness is defined as the time in hours elapsed between the time of usual awakening (even if not in the morning) and the time the subject is as limber as he/she will be during a day involving typical activities. A negative value in duration of morning stiffness change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.
Change From Baseline to Completion/Withdrawal Visit in Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28[ESR])	From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)	DAS28\[ESR\] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x Global Assessment of Arthritis where 28 joints are examined and a lower score indicates less disease activity. A negative value in DAS28\[ESR\] change from Baseline indicates an improvement from Baseline.
Percentage of Subjects With Good European League Against Rheumatism (EULAR) Response at Completion/Withdrawal Visit	From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)	Good EULAR response is defined as Disease Activity Score 28 \[Erythrocyte Sedimentation Rate\] (DAS28\[ESR\]) improvement from Baseline of the preceding double-blind study \> 1.2 and DAS28\[ESR\] value \< 3.2.
Change From Baseline to Completion/Withdrawal Visit in Short-Form Health Survey (SF-36) Item Questionnaire Physical Component Summary (PCS) Score	From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)	The SF-36 is a 36-item generic health status measure that measures 8 general health concepts: Physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Each domain of the eight domains and the summary concept PCS score are scored to yield values between 0 (worst) and 100 (best).
Change From Baseline to Completion/Withdrawal Visit in Short-Form Health Survey (SF-36) Item Questionnaire Mental Component Summary (MCS) Score	From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)	The SF-36 is a 36-item generic health status measure that measures 8 general health concepts: Physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Each domain of the eight domains and the summary concept MCS score are scored to yield values between 0 (worst) and 100 (best).

Trial Locations

Locations (121): 140
🇺🇸
Orlando, Florida, United States
49
🇨🇱
Santiago de Chile, Chile
136
🇺🇸
Tampa, Florida, United States
157
🇺🇸
Coeur d'Alene, Idaho, United States
134
🇺🇸
Wheaton, Maryland, United States
14
🇦🇷
Capital Federal, Argentina
139
🇺🇸
Charleston, South Carolina, United States
32
🇨🇦
Toronto, Ontario, Canada
191
🇭🇺
Debrecen, Hungary
73
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Budapest, Hungary
76
🇭🇺
Miskolc, Hungary
93
🇱🇹
Panevezys, Lithuania
90
🇱🇹
Siauliai, Lithuania
94
🇱🇹
Vilnius, Lithuania
96
🇲🇽
Monterrey, Mexico
211
🇺🇦
Kiev, Ukraine
212
🇺🇦
Kiev, Ukraine
220
🇺🇦
Kiev, Ukraine
208
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Symferopyl, Ukraine
145
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Sarasota, Florida, United States
156
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Lincoln, Nebraska, United States
147
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Cleveland, Ohio, United States
152
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Huntsville, Alabama, United States
153
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Danbury, Connecticut, United States
133
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Ocala, Florida, United States
150
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Orlando, Florida, United States
155
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Springfield, Illinois, United States
151
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Saint Louis, Missouri, United States
135
🇺🇸
Charlotte, North Carolina, United States
190
🇨🇱
Santiago de Chile, Chile
203
🇨🇦
Winnipeg, Canada
57
🇨🇿
Ostrava Trebovice, Czechia
52
🇭🇷
Rijeka, Croatia
56
🇨🇿
Brno, Czechia
60
🇨🇿
Praha 5, Czechia
58
🇨🇿
Uherske Hradiste, Czechia
64
🇪🇪
Parnu, Estonia
62
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Zlin, Czechia
63
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Tartu, Estonia
71
🇭🇺
Budapest, Hungary
75
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Bupadest, Hungary
81
🇮🇱
Haifa, Israel
79
🇮🇱
Afula, Israel
82
🇮🇱
Ashkelon, Israel
83
🇮🇱
Haifa, Israel
78
🇮🇱
Ramat Gan, Israel
85
🇮🇱
Zerifin, Israel
77
🇮🇱
Tel Aviv, Israel
192
🇳🇿
Tauranga, New Zealand
224
🇷🇺
Moscow, Russian Federation
112
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St. Petersburg, Russian Federation
118
🇷🇸
Belgrade, Serbia
122
🇸🇰
Piestany, Slovakia
209
🇺🇦
Donetsk, Ukraine
210
🇺🇦
Dnepropetrovsk, Ukraine
148
🇺🇸
San Diego, California, United States
68
🇫🇮
Hyvinkaa, Finland
13
🇦🇷
Quilmes, Argentina
177
🇧🇪
Merksem, Belgium
187
🇨🇿
Plzen, Czechia
61
🇨🇿
Praha 2, Czechia
215
🇺🇦
Kiev, Ukraine
214
🇺🇦
Zaporozhye, Ukraine
9
🇦🇷
Capital Federal, Argentina
137
🇺🇸
Austin, Texas, United States
12
🇦🇷
Buenos Aires, Argentina
6
🇦🇷
Santa Fe, Argentina
179
🇧🇪
Antwerpen, Belgium
160
🇫🇷
Montpellier Cedex 5, France
86
🇱🇻
Riga, Latvia
18
🇦🇺
Malvern, Australia
221
🇧🇬
Sofia, Bulgaria
44
🇨🇱
Valdivia, Chile
30
🇧🇬
Sofia, Bulgaria
36
🇨🇦
Kitchener, Canada
39
🇨🇦
Toronto, Ontario, Canada
1
🇦🇷
Capital Federal, Argentina
2
🇦🇷
Cordoba, Argentina
7
🇦🇷
Rosario, Argentina
10
🇦🇷
San Miguel de Tucuman, Argentina
26
🇧🇬
Stara Zagora, Bulgaria
143
🇺🇸
San Antonio, Texas, United States
21
🇦🇺
Maroochydore, Australia
74
🇭🇺
Szolnok, Hungary
158
🇺🇸
Dayton, Ohio, United States
199
🇧🇪
Liege, Belgium
29
🇧🇬
Pleven, Bulgaria
8
🇦🇷
Ciudad Autonoma de Buenos Aire, Argentina
11
🇦🇷
Cordoba, Argentina
28
🇧🇬
Sofia, Bulgaria
35
🇨🇦
Hamilton, Canada
201
🇨🇦
Pointe Claire, Canada
23
🇦🇺
Perth, Australia
43
🇨🇦
Newmarket, Ontario, Canada
31
🇨🇦
Sainte Foy, Canada
65
🇪🇪
Tallinn, Estonia
55
🇨🇿
Praha, Czechia
88
🇱🇻
Riga, Latvia
92
🇱🇹
Alytus, Lithuania
89
🇱🇹
Kaunas, Lithuania
91
🇱🇹
Klaipeda, Lithuania
95
🇲🇽
Mexicalli, Mexico
103
🇳🇿
Auckland, New Zealand
101
🇳🇿
Christchurch, New Zealand
100
🇳🇿
South Canterbury, New Zealand
113
🇷🇺
Moscow, Russian Federation
117
🇷🇸
Belgrade, Serbia
119
🇸🇰
Bratislava, Slovakia
121
🇸🇰
Kosice, Slovakia
107
🇷🇺
Moscow, Russian Federation
120
🇸🇰
Piestany, Slovakia
216
🇺🇦
Donetsk, Ukraine
222
🇷🇺
Moscow, Russian Federation
223
🇷🇺
Moscow, Russian Federation
109
🇷🇺
St. Petersburg, Russian Federation
111
🇷🇺
St. Petersburg, Russian Federation
193
🇷🇺
St. Petersburg, Russian Federation
110
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Yaroslavl, Russian Federation
114
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Niska Banja, Serbia
115
🇷🇸
Novi Sad, Serbia
213
🇺🇦
Ivano-Frankivsk, Ukraine