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NCT04557462PHASE3Recruiting

A Rollover Extension Program (REP) to Evaluate the Long-term Safety and Tolerability of Open Label Iptacopan/LNP023 in Participants With Primary IgA Nephropathy

Novartis Pharmaceuticals

Start Date

9/20/2021

Completion Date

12/4/2030

Summary

The purpose of this study is to evaluate the long-term safety and tolerability, of open label iptacopan in primary IgA nephropathy participants who have completed either the CLNP023X2203 or CLNP023A2301 clinical trials. The open-label design of the current study is appropriate to provide study participants the opportunity to receive treatment with iptacopan until marketing authorizations are received and the drug product becomes commercially available while enabling collection of long-term safety and tolerability data for the investigational drug. Furthermore efficacy assessments conducted every 6 months will afford the opportunity to evaluate the clinical effects of iptacopan on long-term disease progression.

Detailed Description

This is an open-label, non-randomized, multicenter roll-over extension program (REP) to: * CLNP023X2203, a Phase II trial investigating the dose ranging effects of LNP023 on efficacy, pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability in primary IgAN patients, and * CLNP023A2301, a Phase III trial, investigating the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of LNP023 in patients with primary IgAN. Subjects completing the CLNP023X2203 and CLNP023A2301 trials on study drug, who want to continue treatment and who meet the inclusion/exclusion requirements of the roll over extension program, will have the opportunity to receive iptacopan until: * 3 years from LPFV of this study CLNP023A2002B, or * the participant no longer derives benefit from iptacopan according to the Investigator, or * the benefit-risk profile of the product in IgAN is no longer positive, or * initiation of maintenance hemodialysis, kidney transplantation or eGFR \< 15 mL/min/1.73m2 , or * the product becomes commercially available in a specific country following product launch and subsequent reimbursement for IgAN, where applicable, or * if a marketing application or reimbursement of an investigational product is rejected/not pursued in a region/country for the indication under study or which ever is sooner

Eligibility Criteria

Age Range: 18 years to 100 years

Inclusion Criteria: * For LNP023X2203, participants must have completed part 1 or part 2 of the trial. For LNP023A2301, participants must have completed the entire core trial defined as the full 24 month treatment period. * eGFR\* ≥ 20 ml/min/1.73m2 \*eGFR calculated using the CKD-EPI formula (or modified MDRD formula according to specific ethnic groups and local practice guidelines) * Per investigator's clinical judgement, the participant may benefit from receiving the open-label treatment of iptacopan 200 mg b.i.d. * Prior Vaccination against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae infections should be up to date (i.e. any boosters required administered according to local regulations. * All participants must be on supportive care regimen of ACEi or ARB\* as per KDIGO guidelines. * participants who are not taking KDIGO guideline doses because they have documented allergies or intolerance to ACEi and ARB are eligible for the study Exclusion Criteria: * participants who screen or baseline failed in the CLNP023X2203 Part 1 or Part 2, or CLNP023A2301 studies or who prematurely withdrew from either study for any reason. * Evidence of severe urinary obstruction or difficulty in voiding; any urinary tract disorder other than IgAN at screening and before dosing with LNP023. * Current (within 4 weeks of study drug administration in the REP) acute kidney injury (AKI) * Presence of Rapidly Progressive Glomerulonephritis (RPGN) as defined by 50% decline in eGFR within the last 3 months. * Participants treated with immunosuppressive or other immunmodulatory agents such as but not limited to cyclophosphamide, rituximab, infliximab, eculizumab, canakinumab, mycophenolate mofetil (MMF) or mycophenolate sodium (MPS), cyclosporine, tacrolimus, sirolimus, everolimus and/or systemic corticosteroids exposure (\>7.5 mg/d prednisone/prednisolone equivalent) within 5 half-lives of respective medication or 90 days prior to first study drug administration, whichever is shorter. Rituximab requires 180 days wash out. * Use of other investigational drugs at the time of enrolment, or within 5 half-lives of enrolment or within 30 days whichever is longer. * History of recurrent invasive infections caused by encapsulated organisms, such as meningococcus and pneumococcus.

Interventions

DRUG

LNP023

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Conditions

Primary IgA Nephropathy

Locations

AZ Kidney Dise and Hypertension Ctr

Glendale, Arizona 85306

United States

Kaiser Permanente

San Diego, California 92111

United States

North America Research Institute

San Dimas, California 91773

United States

University of Colorado Anschutz

Aurora, Colorado 80045

United States

Nephrology Associates PA

Newark, Delaware 19713

United States

CaRe Research

Chubbuck, Idaho 83202

United States

Nep Assoc of Northern Illinois

Hinsdale, Illinois 60521

United States

Johns Hopkins Hospital

Baltimore, Maryland 21287

United States

Brigham and Womens Hosp Harvard Med School

Boston, Massachusetts 02115

United States

Mayo Clinic Rochester

Rochester, Minnesota 55905

United States

Clin Rsrch Consult a JCCT Company

Kansas City, Missouri 64112

United States

DaVita Clinical Research

Las Vegas, Nevada 89146

United States

New Jersey Kidney Care

Jersey City, New Jersey 07305

United States

Col Uni Med Center New York Presby

New York, New York 10032

United States

Dallas Renal Group

Dallas, Texas 75230

United States

Prolato Clinical Research Center

Houston, Texas 77054

United States

Novartis Investigative Site

Córdoba, Córdoba Province X5016KEH

Argentina

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Córdoba, Córdoba Province X5016KET

Argentina

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CABA, C1181ACH

Argentina

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CABA, C1426ABP

Argentina

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Santa Fe, S3000EPV

Argentina

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Woolloongabba, Queensland 4102

Australia

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Adelaide, South Australia 5000

Australia

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Parkville, Victoria 3065

Australia

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Roeselare, West Vlaanderen 8800

Belgium

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Edegem, 2650

Belgium

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Leuven, 3000

Belgium

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Belo Horizonte, Minas Gerais 30150-221

Brazil

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Curitiba, Paraná 80440-020

Brazil

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Porto Alegre, Rio Grande do Sul 90035-074

Brazil

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São José do Rio Preto, São Paulo 15090 000

Brazil

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São Paulo, São Paulo 04038-002

Brazil

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São Paulo, São Paulo 05403-000

Brazil

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Oshawa, Ontario L1G 2B9

Canada

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Temuco, 4781151

Chile

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Beijing, Beijing Municipality 100013

China

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Beijing, Beijing Municipality 102218

China

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Guangzhou, Guangdong 510080

China

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Luoyang, Henan 471003

China

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Zhengzhou, Henan 450003

China

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Changsha, Hunan 410011

China

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Changchun, Jilin 130041

China

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Yinchuan, Ningxia 750004

China

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Taiyuan, Shanxi 030001

China

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Xian, Shanxi 710061

China

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Ürümqi, Xinjiang 830001

China

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Ningbo, Zhejiang 315016

China

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Wenzhou, Zhejiang 325000

China

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Beijing, 100034

China

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Guangzhou, 510080

China

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Ningbo, 315010

China

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Qingdao, 266000

China

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Shanghai, 200025

China

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Shanghai, 200040

China

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Shenzhen, 518036

China

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Medellín, Antioquia 050001

Colombia

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Barranquilla, Atlántico 080020

Colombia

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Prague, 128 08

Czechia

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Aalborg, 9000

Denmark

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Aarhus N, 8200

Denmark

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Copenhagen, 2100

Denmark

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Odense C, 5000

Denmark

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Marseille, 13005

France

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Montpellier, 34295

France

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Paris, 75015

France

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Freiburg im Breisgau, Baden-Wurttemberg 79106

Germany

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Stuttgart, Baden-Wurttemberg 70376

Germany

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Aachen, 52074

Germany

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Berlin, 13353

Germany

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Essen, 45147

Germany

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Hanover, 30625

Germany

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Heidelberg, 69120

Germany

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Kiel, 24105

Germany

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Magdeburg, 39120

Germany

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Mainz, 55131

Germany

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Tübingen, 72076

Germany

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Ulm, 89081

Germany

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Hong Kong, Hong Kong 999077

Hong Kong

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Pécs, Baranya 7623

Hungary

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Debrecen, Hajdu Bihar Megye 4032

Hungary

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Bangalore, Karnataka 560004

India

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New Delhi, National Capital Territory of Delhi 110017

India

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New Delhi, National Capital Territory of Delhi 110029

India

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Hyderabad, Telangana 500082

India

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Ashkelon, 7830604

Israel

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Jerusalem, 9112001

Israel

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Petah Tikva, 4941492

Israel

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Bologna, BO 40138

Italy

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Naples, 80131

Italy

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Kasugai, Aichi-ken 4868510

Japan

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Toyoake, Aichi-ken 4701192

Japan

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Toyota, Aichi-ken 4718513

Japan

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Sapporo, Hokkaido 0068555

Japan

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Sapporo, Hokkaido 0608604

Japan

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Kawasaki, Kanagawa 2138587

Japan

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Yokohama, Kanagawa 2248503

Japan

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Yokohama, Kanagawa 2360004

Japan

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Kyoto, Kyoto 6050981

Japan

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Sendai, Miyagi 9813205

Japan

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Matsumoto, Nagano 3908621

Japan

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Osaka, Osaka 5340021

Japan

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Ōmihachiman, Shiga 5230082

Japan

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Chiba, 2608712

Japan

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Niigata, 9518520

Japan

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Okayama, 7008558

Japan

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Osaka, 5300012

Japan

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Osaka, 5308480

Japan

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Kuala Lumpur, Kuala Lumpur 50586

Malaysia

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Kuala Lumpur, 59100

Malaysia

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Benito Juárez, Mexico City 03100

Mexico

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Querétaro, 76000

Mexico

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Groningen, Provincie Groningen 9713 GZ

Netherlands

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Nordbyhagen, Oslo 1478

Norway

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Bergen, NO-5021

Norway

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Rostov-on-Don, 344022

Russia

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Saint Petersburg, 197110

Russia

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Singapore, 119074

Singapore

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Singapore, 169608

Singapore

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Košice, 040 11

Slovakia

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Maribor, Slovenia 2000

Slovenia

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Ljubljana, 1000

Slovenia

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Bloemfontein, Free State 9301

South Africa

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Bundang Gu, Gyeonggi-do 13620

South Korea

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Seoul, Korea 02841

South Korea

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Seoul, Korea 03312

South Korea

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Cheongju-si, North Chungcheong 28644

South Korea

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Seoul, Seoul 03080

South Korea

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Busan, 47392

South Korea

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Seoul, 03722

South Korea

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Seoul, 05278

South Korea

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Seoul, 06591

South Korea

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Seoul, 06973

South Korea

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Taegu, 41944

South Korea

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Pamplona, Navarre 31008

Spain

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Barcelona, 08036

Spain

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Salamanca, 37007

Spain

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Stockholm, 141 86

Sweden

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Kaohsiung City, 833

Taiwan

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New Taipei City, 22060

Taiwan

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New Taipei City, 23561

Taiwan

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Taichung, 40447

Taiwan

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Taichung, 407219

Taiwan

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Taipei, 10002

Taiwan

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Taoyuan, 33305

Taiwan

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Bangkok, 10330

Thailand

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Bangkok, 10400

Thailand

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Bangkok, 10700

Thailand

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Istanbul, Fatih 34098

Turkey (Türkiye)

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Köseköy, Kocaeli 41380

Turkey (Türkiye)

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Antalya, Konyaalti 07070

Turkey (Türkiye)

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Kayseri, Melikgazi 38039

Turkey (Türkiye)

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Istanbul, Sariyer 34396

Turkey (Türkiye)

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Ankara, Yenimahalle 06500

Turkey (Türkiye)

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Mersin, Yenisehir 33110

Turkey (Türkiye)

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Newcastle upon Tyne, Tyne and Wear NE7 7DN

United Kingdom

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Cambridge, CB2 0QQ

United Kingdom

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Leicester, LE5 4PW

United Kingdom

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London, SE5 9RS

United Kingdom

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Salford, M6 8HD

United Kingdom

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Ho Chi Minh City, VNM 700000

Vietnam

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Ho Chi Minh City, 700000

Vietnam