MedPath

A Phase 2/3 Study of Efgartigimod PH20 SC in Adult Participants with Bullous Pemphigoid

Phase 2
Completed
Conditions
Bullous Pemphigoid
Interventions
Other: placebo
Biological: efgartigimod PH20 SC
Registration Number
NCT05267600
Lead Sponsor
argenx
Brief Summary

ARGX-113-2009 is an operationally seamless 2-part, phase 2/3, prospective, global, multicenter, randomized, double-blinded, placebo-controlled study to investigate the efficacy, safety, tolerability, immunogenicity, participant-reported outcome measures (including those assessing participant QoL), PK, and PD of efgartigimod PH20 SC administered via subcutaneous (SC) injection in adult participants with moderate to severe BP. This study intends to demonstrate that efgartigimod is an effective and safe treatment for BP, providing participants with control of disease activity (CDA) and eventually remission while reducing their cumulative exposure to OCS.

study will consist of 2 parts:

* Part A of the study is a phase 2 evaluation that intends to provide proof of concept for the therapeutic activity of efgartigimod PH20 SC in participants with BP.

* Part B of the study is a phase 3 evaluation that intends to confirm the results obtained from part A in a separate, larger group of participants with BP.

An interim analysis will be performed during part A (on data obtained through week 26 for all Part A participants) to assess the primary endpoint and several secondary endpoints, confirm the appropriate sample size for part B of the study, and determine whether the efficacy results observed through week 26 of part A warrant continued study of efgartigimod PH20 SC for the treatment of participants with BP (futility analysis).

Other than differences in main goals, endpoints, and statistical analyses, parts A and B are identical in schedule, structure, assessments, and conduct.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
98
Inclusion Criteria
  • The participant is willing and able to do the following:

    1. understand the requirements of the study
    2. provide written informed consent
    3. comply with the study protocol procedures.
  • The participant is male or female and has reached the age of consent at the time of signing the informed consent form (ICF).

  • Participants have clinical signs of BP.

  • Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies and: Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline before study intervention can be administered.

The full list of inclusion criteria can be found in the protocol.

Exclusion Criteria
  • Other forms of pemphigoid or other autoimmune bullous diseases (AIBDs).
  • Received unstable dose of treatments known to cause or exacerbate BP for at least 4 weeks prior to the baseline visit
  • Use of BP treatments other than oral corticosteroids (OCS), topical corticosteroids (TCS), conventional immunosuppressants or dapsone.
  • Known contraindication to OCS therapy
  • Active, chronic or latent infection at screening
  • Positive COVID-19 test result at screening (testing performed if required per local regulations).
  • History of malignancy unless deemed cured by adequate treatment with no evidence of recurrence for ≥3 years before the first administration of the IMP. Participants with the following cancers can be included at any time, provided they are adequately treated prior to their participation in the study: Basal cell or squamous cell skin cancer, Carcinoma in situ of the cervix, Carcinoma in situ of the breast, Incidental histological finding of prostate cancer
  • Clinical evidence of other significant serious diseases, have had a recent surgery, or who have any other condition that, in the opinion of the investigator, could confound the results of the study or put the patient at undue risk or prevent participants from complying with protocol requirements
  • Use of an investigational product within 3 months before the first dose of IMP
  • Previously participated in a clinical study with efgartigimod or currently participating in another interventional clinical study
  • Known hypersensitivity to any of the components of the administered treatments
  • Positive serum test at screening for an active infection: HBV, HCV, HIV
  • Current or history (ie, within 12 months of screening) of alcohol, drug, or medication abuse as assessed by the investigator
  • Pregnant or lactating females and those who intend to become pregnant during the study
  • Live or live-attenuated vaccine received <4 weeks before baseline visit

The full list of exclusion criteria can be found in the protocol.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
efgartigimod PH20 SCPrednisoneparticipants receiving efgartigimod PH20 SC on top of Prednisone
placebo PH20 SCplaceboparticipants receiving placebo PH20 SC on top of Prednisone
efgartigimod PH20 SCefgartigimod PH20 SCparticipants receiving efgartigimod PH20 SC on top of Prednisone
placebo PH20 SCPrednisoneparticipants receiving placebo PH20 SC on top of Prednisone
Primary Outcome Measures
NameTimeMethod
Proportion of participants who are in complete remission (CR) while receiving efgartigimod PH20 SC or placebo and have been off oral corticosteroid (OCS) therapy for ≥8 weeks at week 36at week 36
Secondary Outcome Measures
NameTimeMethod
Cumulative dose of oral corticosteroid (OCS) from baseline to week 36up to week 36
EuroQol 5-Dimension 5-Level (EQ-5D-5L) scores over timeup to week 36
Proportion of participants who achieve an Investigator Global Assessment of Bullous Pemphigoid (IGA-BP) score of 0 while receiving efgartigimod PH20 SC or placebo and have been off oral corticosteroid (OCS) therapy for ≥8 weeks at week 36at week 36
Proportion of participants who achieve an Investigator Global Assessment of Bullous Pemphigoid (IGA-BP) score of 0 or 1 while receiving efgartigimod PH20 SC or placebo and have been off oral corticosteroid (OCS) therapy for ≥8 weeks at week 36at week 36
Proportion of participants who achieve an Investigator Global Assessment of Bullous Pemphigoid (IGA-BP) score of 0 or 1 while receiving efgartigimod PH20 SC or placebo at any time through week 36up to week 36
Changes from baseline in the Bullous Pemphigoid Disease Area Index (BPDAI) activity scoreup to week 36
Proportion of participants who are in complete remission (CR) while receiving efgartigimod PH20 SC or placebo and have been receiving minimal oral corticosteroid (OCS) therapy for ≥8 weeks at week 36at week 36

Minimal oral corticosteroid (OCS) therapy is defined as ≤0.1 mg/kg/day of prednisone (or an equivalent dose of another OCS).

Time to achieve control of disease activity (CDA)up to week 36
Time to achieve complete remission (CR)up to week 36
Time to achieve complete remission (CR) while on minimal oral corticosteroid (OCS) therapy for ≥8 weeksup to week 36
Time to achieve complete remission (CR)/partial remission (PR) while off oral corticosteroid (OCS) therapy for ≥8 weeksup to week 36
Time to achieve complete remission (CR) while off oral corticosteroid (OCS) therapy for ≥8 weeksup to week 36
Time to achieve relapseup to week 36
Cumulative oral corticosteroid (OCS) dose for the participant at the time points when they exhibit control of disease activity (CDA)up to week 36
Cumulative oral corticosteroid (OCS) dose for the participant at the time points when they exhibit complete remission (CR)up to week 36
Cumulative oral corticosteroid (OCS) dose for the participant at the time points when they exhibit complete remission (CR) while on minimal oral corticosteroid (OCS) therapy for ≥8 weeksup to week 36
Cumulative oral corticosteroid (OCS) dose for the participant at the time points when they exhibit complete remission (CR)/partial remission (PR) while off oral corticosteroid (OCS) therapy for ≥8 weeksup to week 36
Cumulative oral corticosteroid (OCS) dose for the participant at the time points when they exhibit complete remission (CR) while off oral corticosteroid (OCS) therapy for ≥8 weeksup to week 36
Cumulative oral corticosteroid (OCS) dose for the participant at the time points when they exhibit relapseup to week 36
Proportion of participants who receive rescue therapy before week 36at week 36
Proportion of participants who achieve control of disease activity (CDA) while receiving efgartigimod PH20 SC or placebo and remain free of relapse through week 36up to week 36
Changes from baseline in the 24-hour average itch score from the Itch Numerical Rating Scale (Itch NRS)up to week 36
Changes from baseline in the 24-hour worst itch score from the Itch Numerical Rating Scale (Itch NRS)up to week 36
Incidence of treatment emergent adverse events (TEAEs)up to 46 weeks
Severity of treatment emergent adverse events (TEAEs)up to 46 weeks
Incidence of adverse events of special interest (AESIs)up to 46 weeks
Severity of adverse events of special interest (AESIs)up to 46 weeks
Incidence of serious adverse events (SAEs)up to 46 weeks
Severity of serious adverse events (SAEs)up to 46 weeks
The Aggregate Improvement Score (AIS) from the Glucocorticoid Toxicity Index (GTI)up to week 36
The Cumulative Worsening Score (CWS) from the Glucocorticoid Toxicity Index (GTI)up to week 36
The Glucocorticoid Toxicity Index Specific List (GTI-SL)up to week 36
Dermatology Life Quality Index (DLQI) scores over timeup to week 36
Autoimmune Bullous Disease Quality of Life (ABQoL) scores over timeup to week 36
Efgartigimod serum concentrationsup to week 43
Percent change of total IgG serum levels from baseline over timeup to 46 weeks
Percent change of Anti-BP180 and anti-BP230 antibodies from baseline over timeup to 46 weeks
Incidence of Antidrug antibodies (ADA) against efgartigimod (in serum) and antibodies produced against rHuPH20 (in plasma)up to 46 weeks
Number of participants (or their caregivers) who complete the (self-)administration training at study sitesup to week 32
Percentage of participants (or their caregivers) who complete the (self-)administration training at study sitesup to week 32
Number of participants (or their caregivers) who are determined by site staff to be sufficiently competent in (self-)administering efgartigimod PH20 SCup to week 32
Percentage of participants (or their caregivers) who are determined by site staff to be sufficiently competent in (self-)administering efgartigimod PH20 SCup to week 32
Number of participants (or their caregivers) who successfully (self-)administer efgartigimod PH20 SC under site staff supervisionup to week 35
Percentage of participants (or their caregivers) who successfully (self-)administer efgartigimod PH20 SC under site staff supervisionup to week 35

Trial Locations

Locations (129)

Investigator site 121 - US0010092

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Redwood City, California, United States

Investigator site 115 - US0010157

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Jackson, Mississippi, United States

Investigator site 34 - US0010182

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Houston, Texas, United States

Investigator site 108 - CN0860023

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Fujian, China

Investigator site 91 - CN0860017

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Beijing, China

Investigator site 107 - CN0860021

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Guangzhou, China

Investigator site 128 - CN0860097

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Hefei, China

Investigator site 109 - CN0860025

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Wuhan, China

Investigator site 15 - BG3590020

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Stara Zagora, Bulgaria

Investigator site 11 - HU0360003

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Debrecen, Hungary

Investigator site 84 - RS3810010

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Belgrad, Serbia

Investigator site 113 - SK4210002

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Bratislava, Slovakia

Investigator site 59 - GR0300005

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Thessaloníki, Greece

Investigator 68 - RS381011

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Belgrade, Serbia

Investigator site 67 - RS3810012

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Niš, Serbia

Investigator site 76 - GR030003

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Chaïdári, Greece

Investigator site 88 - LV3710004

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Riga, Latvia

Investigator site 120 - SK4210004

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Košice, Slovakia

Investigator site 19 - PL0480046

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Wrocław, Poland

Investigator site 2 - US0010087

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Boca Raton, Florida, United States

Investigator site 10 - US0010153

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Castle Rock, Colorado, United States

Investigator site 25 - US0010158

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Pittsburgh, Pennsylvania, United States

Investigator site 5 - US0010088

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Buffalo, New York, United States

Investigator site 85 - US0010159

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Lebanon, New Hampshire, United States

Investigator site 4 - US0010137

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Fairborn, Ohio, United States

Investigator site 28 - BG3590018

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Sofia, Bulgaria

Investigator site 14 - BG3590010

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Sofia, Bulgaria

Investigator site 3 - US0010151

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Morgantown, West Virginia, United States

Investigator site 27 - AU0610006

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Kogarah, Australia

Investigator site 125 - AU0610019

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Woolloongabba, Australia

Investigator site 116 - CN0860027

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Chongqing, China

Investigator site 118 - CZ4200016

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Hradec Králové, Czechia

Investigator site 124 - CN0860098

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Nanchang, China

Investigator site 94 - CN0860066

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Nanyang, China

Investigator site 127 - CN860020

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Shangai, China

Investigator site 123 - CN0860095

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Shanghai, China

Investigator site 126 - CN0860026

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Zhengzhou, China

Investigator site 37 - HR3850001

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Zagreb, Croatia

Investigator site 38 - FR0330040

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Nice, France

Investigator site 29 - FR0330029

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Rouen, France

Investigator site 97 - CZ4200015

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Brno, Czechia

Investigator site 45 - DE0490001

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Marburg, Germany

Investigator site 60 - GE0300004

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Athens, Greece

Investigator site 58 - GR0300001

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Athens, Greece

Investigator site 61 - GE0300002

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Thessaloníki, Greece

Investigator site 55 - DE0490026

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Würzburg, Germany

Investigator site 51 - DE0490008

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Essen, Germany

Investigator site 75 - DE0490047

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München, Germany

Investigator site 63 - IL9720018

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Haifa, Israel

Investigator site 39 - IL9720003

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Afula, Israel

Investigator site 129 - JP0810073

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Niigata, Japan

Investigator site 81 - IT0390030

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Genova, Italy

Investigator site 77 - IT0390062

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Milano, Italy

Investigator site 99 - JP0810050

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Kurume, Japan

Investigator site 87 - LV3710005

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Riga, Latvia

Investigator site 82 - LV3710003

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Riga, Latvia

Investigator site 66 - NL0310015

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Groningen, Netherlands

Investigator site 102 - JP0810069

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Ōsaka-sayama, Japan

Investigator site 79 - PL0480025

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Rzeszów, Poland

Investigator site 83 - PL0480050

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Warsaw, Poland

Investigator site 18 - PL0480048

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Wrocław, Poland

Investigator site 17 - PL0480047

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Łódź, Poland

Investigator site 90 - RO0400014

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Cluj-Napoca, Romania

Investigator site 89 - RO0400015

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Iaşi, Romania

Investigator site 12 - ES0340025

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Madrid, Spain

Investigator 20 - ES0340029

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Madrid, Spain

Investigator site 44 - UK0440037

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Southampton, United Kingdom

Investigator site 49 - ES0340058

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Manises, Spain

Investigator site 70 - ES0340061

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Valencia, Spain

Investigator site 9 - ES0340052

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Sevilla, Spain

Investigator site 43 - IT0390060

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Brescia, Italy

Investigator site 64 - IT0390061

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Pavia, Italy

Investigator site 30 - IT0390040

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Siena, Italy

Investigator site 23 - IT0390006

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Roma, Italy

Investigator site 42 - IT0390005

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Roma, Italy

Investigator site 33 - UK0440022

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Bristol, United Kingdom

Investigator site 103 - JP0810070

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Kumamoto, Japan

Investigator site 104 - JP0810071

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Maebashi, Japan

Investigator site 100 - JP0810046

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Nagakute, Japan

Investigator site 101 - JP0810049

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Osaka, Japan

Investigator site 112 - JP0810045

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Sapporo, Japan

Investigator site 105 - JP0810067

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Sendai, Japan

Investigator site 74 - US0010178

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Phoenix, Arizona, United States

Investigator site 6 - US0010138

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Fountain Valley, California, United States

Investigator site 72 - US0010186

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Santa Monica, California, United States

Investigator site 21 - US0010152

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Clearwater, Florida, United States

Investigator site 13 - US0010155

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West Lafayette, Indiana, United States

Investigator site 1 - US0010017

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Miami, Florida, United States

Investigator site 73 - US0010098

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Saint Louis, Missouri, United States

Investigator site 93 - US0010169

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New York, New York, United States

Investigator site 92 - US0010150

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Murray, Utah, United States

Investigator site 111 - CN0860064

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Beijing, China

Investigator site 95 - CN0860018

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Chengdu, China

Investigator site 110 - CN0860053

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Guanzhou, China

Investigator site 122 - CN0860065

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Ürümqi, China

Investigator site 22 - HR3850003

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Split, Croatia

Investigator site 16 - HR3850002

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Zagreb, Croatia

Investigator site 117 - CZ4200013

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Plzen-Bory, Czechia

Investigator site 56 - DE0490028

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Kiel, Germany

Investigator site 96 - CZ4200012

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Prague, Czechia

Investigator site 80 - DE0490041

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Düsseldorf, Germany

Investigator site 46 - DE0490039

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Berlin, Germany

Investigator site 52 - DE0490024

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Frankfurt am main, Germany

Investigator site 57 - DE0490046

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Erlangen, Germany

Investigator site 54 - DE0490030

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Dresden, Germany

Investigator site 53 - DE0490023

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Freiburg, Germany

Investigator site 62 - GE0300006

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Athens, Greece

Investigator site 26 - HU0360023

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Budapest, Hungary

Investigator site 7 - HU0360008

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Pécs, Hungary

Investigator site 41 - IL9720001

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Ramat Gan, Israel

Investigator site 65 - IT0390055

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Bologna, Italy

Investigator site 40 - IL9720002

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Tel Aviv, Israel

Investigator site 78 - IT0390039

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Catania, Italy

Investigator site 47 - IT0390031

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Firenze, Italy

Investigator site 86 - IT0390067

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Firenze, Italy

Investigator site 114 - SK4210003

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Trnava, Slovakia

Investigator site 119 - IT0390066

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Parma, Italy

Investigator site 98 - JP0810043

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Tokyo, Japan

Investigator site 106 - JP0810068

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Yokohama, Japan

Investigator site 32 - ES0340050

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Badalona, Spain

Investigator site 69 - RS3810009

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Novi Sad, Serbia

Investigator 24 - ES0340051

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Barcelona, Spain

Investigator site 8 - ES0340053

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Granada, Spain

Investigator site 48 - ES0340059

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Mieres, Spain

Investigator site 31 - ES0340057

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Málaga, Spain

Investigator site 71 - UK0440036

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London, United Kingdom

Investigator site 36 - AU0610013

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Fitzroy, Australia

Investigator site 50 - US0010149

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Ann Arbor, Michigan, United States

Investigator site 35 - US0010156

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Louisville, Kentucky, United States

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