A Study of Baricitinib (LY3009104) in Combination With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis
- Conditions
- Atopic Dermatitis
- Interventions
- Registration Number
- NCT03733301
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
The purpose of this study is to evaluate the efficacy and safety of baricitinib in combination with topical corticosteroids (TCS) in participants with moderate to severe atopic dermatitis.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 329
- Have been diagnosed with moderate to severe atopic dermatitis for at least 12 months.
- Have had inadequate response to existing topical (applied to the skin) medications within 6 months preceding screening.
- Are willing to discontinue certain treatments for eczema (such as systemic and topical treatments during a washout period).
- Agree to use emollients daily.
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Are currently experiencing or have a history of other concomitant skin conditions (e.g., psoriasis or lupus erythematosus), or a history of erythrodermic, refractory, or unstable skin disease that requires frequent hospitalizations and/or intravenous treatment for skin infections.
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A history of eczema herpeticum within 12 months, and/or a history of 2 or more episodes of eczema herpeticum in the past.
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Participants who are currently experiencing a skin infection that requires treatment, or is currently being treated, with topical or systemic antibiotics.
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Have any serious illness that is anticipated to require the use of systemic corticosteroids or otherwise interfere with study participation or require active frequent monitoring (e.g., unstable chronic asthma).
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Have been treated with the following therapies:
- Monoclonal antibody for less than 5 half-lives prior to randomization.
- Received prior treatment with any oral Janus kinase (JAK) inhibitor less than 4 weeks prior to randomization.
- Received any parenteral corticosteroids administered by intramuscular or intravenous (IV) injection within 6 weeks prior to planned randomization or are anticipated to require parenteral injection of corticosteroids during the study.
- Have had an intra-articular corticosteroid injection within 6 weeks prior to planned randomization.
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Have high blood pressure characterized by a repeated systolic blood pressure >160 millimeters of mercury (mm Hg) or diastolic blood pressure >100 mm Hg.
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Have had major surgery within the past eight weeks or are planning major surgery during the study.
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Have experienced any of the following within 12 weeks of screening: venous thromboembolic event (VTE), myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage III/IV heart failure.
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Have a history of recurrent (≥2) VTE or are considered at high risk of VTE as deemed by the investigator.
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Have a history or presence of cardiovascular, respiratory, hepatic, chronic liver disease gastrointestinal, endocrine, hematological, neurological, lymphoproliferative disease or neuropsychiatric disorders or any other serious and/or unstable illness.
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Have a current or recent clinically serious viral, bacterial, fungal, or parasitic infection including herpes zoster, tuberculosis.
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Have specific laboratory abnormalities.
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Have received certain treatments that are contraindicated.
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Pregnant or breastfeeding.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 4 Milligram (mg) Baricitinib Placebo 4 mg Baricitinib administered orally once daily in combination with topical corticosteroids (TCS). Placebo administered orally once daily to match 2 mg Baricitinib. 2 mg Baricitinib Baricitinib 2 mg Baricitinib administered orally once daily in combination with TCS. Placebo administered orally once daily to match 4 mg Baricitinib. 2 mg Baricitinib Topical corticosteroid 2 mg Baricitinib administered orally once daily in combination with TCS. Placebo administered orally once daily to match 4 mg Baricitinib. 4 Milligram (mg) Baricitinib Topical corticosteroid 4 mg Baricitinib administered orally once daily in combination with topical corticosteroids (TCS). Placebo administered orally once daily to match 2 mg Baricitinib. 2 mg Baricitinib Placebo 2 mg Baricitinib administered orally once daily in combination with TCS. Placebo administered orally once daily to match 4 mg Baricitinib. Placebo Topical corticosteroid Placebo administered orally once daily in combination with TCS. Placebo Placebo Placebo administered orally once daily in combination with TCS. 4 Milligram (mg) Baricitinib Baricitinib 4 mg Baricitinib administered orally once daily in combination with topical corticosteroids (TCS). Placebo administered orally once daily to match 2 mg Baricitinib.
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement Week 16 The IGA measures investigators global assessment of the participant's overall severity of their atopic dermatitis (AD), based on a static, numeric 5-point scale from 0 (clear skin) 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
- Secondary Outcome Measures
Name Time Method Change From Baseline on the Hospital Anxiety Depression Scale (HADS) Baseline, Week 16 The HADS is a participant-rated instrument used to assess both anxiety and depression. This instrument consists of 14 item questionnaire, each item is rated on a 4-point scale, giving maximum scores of 21 for anxiety and depression. Scores of 11 or more on either subscale are considered to be a significant 'case' of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7, 'normal.'
LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75) Week 16 The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3)oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with a visual analogue scales (VAS) where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), \& subjective symptoms (C: 0-20) combine using A/5 + 7\*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. The SCORAD75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the SCORAD score.
Percentage of Participants Achieving IGA of 0 Week 16 The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Change From Baseline in SCORAD Baseline, Week 16 The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with VAS where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease (A: 0-1-2), disease severity (B: 0-18), \& subjective symptoms (C: 0-20) combine using A/5 + 7\*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease.
LS Means were calculated using a MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by- visit-interaction as fixed continuous effects.Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment Week 16 Percentage of participants developing skin infections requiring antibiotic treatment.
Change From Baseline on the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm Baseline, Week 16 The EQ-5D-5L is a 2-part measurement. The first part is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using the United Kingdom (UK) algorithm, with scores ranging from -0.594 to 1, and the United States (US) algorithm, with scores ranging from -0.109 to 1, with higher score indicating better health state.
LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) Week 16 The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI75 is defined as a ≥ 75% improvement from baseline in the EASI score.
Percentage of Participants Achieving a 4-Point Improvement in Itch Numeric Rating Scale (NRS) Week 16 The Itch NRS is a patient-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participant's itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours.
Percentage of Participants Achieving EASI90 Week 16 The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI90 is defined as a ≥ 90% improvement from baseline in the EASI score.
Percent Change From Baseline on EASI Score Baseline, Week 16 The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe).
Least Squares Mean (LSM) were calculated using mixed model repeated measures (MMRM) with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit interaction as fixed categorical effects and baseline score and baseline score-by-visit interaction as fixed continuous effects.Percentage of Participants Achieving EASI50 Week 16 The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs affected: 0 = 0%; 1 = 1-9%; 2 = 10-29%; 3 = 30-49%; 4 = 50-69%; 5 = 70-89%; 6 = 90-100% and the severity of 4 clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head/neck, trunk, upper limbs, and lower limbs). Half scores are allowed between severities 1, 2, and 3. The final EASI score was obtained by weight-averaging these 4 scores and will range from 0 to 72 (severe). The EASI50 is defined as a ≥ 50% improvement from baseline in the EASI score.
Mean Gram Quantity of Moderate Potency Background Topical Corticosteroid (TCS) Used (Tube Weights) Week 0 through Week 16 Average weights of full tubes were used to determine the dispensed weights for each region. Returned tubes were weighed with cap without carton to determine the amount of TCS in grams (g) used at each visit. Analysis was done via analysis of variance (ANOVA), with geographic region, baseline disease severity (IGA) and treatment as factors in the model.
Percent Change From Baseline in Itch NRS Baseline, Week 16 The Itch NRS is a participant-administered, 11-point horizontal scale, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participant's itching is indicated by selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours.
LS Means were calculated using MMRM model with treatment, region, baseline disease severity, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-interaction as fixed continuous effects.Change From Baseline in the Total Score of the Patient Oriented Eczema Measure (POEM) Baseline, Week 16 The POEM is a 7-item self-assessment questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) on a scale ranging from 0-4 (0 = no days, 1 = 1-2 days, 2 = 3-4 days, 3 = 5-6 days, 4 = everyday). The sum of the 7 items gives the total POEM score of 0 (absent disease) to 28 (severe disease). High scores are indicative of more severe disease and poor quality of life.
LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.Change From Baseline in the Patient Global Impression of Severity-Atopic Dermatitis (PGI-S-AD) Score Baseline, Week 16 The PGI-S-AD is a single-item question asking the participant how they would rate their overall AD symptoms over the past 24 hours, using a daily diary. The 5 categories of responses are "(0) no symptoms", "(1) very mild", "(2) mild" "(3) moderate", and "(4) severe."
LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.Change From Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS) Baseline, Week 16 The ADSS is a 3-item, participant-administered questionnaire developed to assess the impact of itch on sleep including difficulty falling asleep due to itch, frequency of waking due to itch, and difficulty getting back to sleep last night due to itch. Item 2 frequency of waking last night is reported by selecting the number of times they woke up each night, ranging from 0 to 29 times, where the higher a number indicates a worse outcome. The ADSS is designed to be completed daily, using a daily diary, with respondents thinking about sleep "last night." Each item is scored individually. LS Mean were calculated using a MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit interaction as fixed categorical effects and baseline score and baseline score-by-visit interaction as fixed continuous effects.
Change From Baseline in Skin Pain NRS Baseline, Week 16 Skin Pain NRS is a patient-administered,11-point horizontal scale anchored at 0 and 10, with 0 representing "no pain" and 10 representing "worst pain imaginable." Overall severity of a participant's skin pain is indicated by selecting the number, using a daily diary, that best describes the worst level of skin pain in the past 24 hours. LS Means were calculated using a MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by- visit-interaction as fixed continuous effects.
Percentage of Participants Achieving SCORAD90 Week 16 The SCORAD index uses the rule of nines to assess disease extent and evaluates 6 clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3)oozing/crusts, (4) excoriation, (5) lichenification, and (6) dryness on a scale of 0 to 3 (0=absence, 1=mild, 2=moderate, 3=severe). The SCORAD index also assesses subjective symptoms of pruritus and sleep loss with VAS where 0 is no itching or no trouble sleeping and 10 is unbearable itching or a lot of trouble sleeping. These 3 aspects: extent of disease: (A: 0-1-2), disease severity (B: 0-18), \& subjective symptoms (C: 0-20) combine using A/5 + 7\*B/2+ C to give a maximum possible score of 103, where 0 = no disease and 103 = severe disease. The SCORAD90 is defined as a ≥ 90% improvement from baseline in the SCORAD score.
Change From Baseline in Body Surface Area (BSA) Affected Baseline, Week 16 The BSA affected by AD will be assessed for 4 separate body regions and is collected as part of the EASI assessment: head and neck, trunk (including genital region), upper extremities, and lower extremities (including the buttocks). Each body region will be assessed for disease extent ranging from 0% to 100% involvement. The overall total percentage will be reported based off of all 4 body regions combined, after applying specific multipliers to the different body regions to account for the percent of the total BSA represented by each of the 4 regions. Use the percentage of skin affected for each region (0 to 100%) in EASI as follows: BSA Total = 0.1\*BSAhead and neck + 0.3\*BSAtrunk + 0.2\* BSAupper limbs + 0.4\*BSAlower limbs.
LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.Change From Baseline on the Work Productivity and Activity Impairment - Atopic Dermatitis (WPAI-AD) Questionnaire Baseline, Week 16 The WPAI-AD participant questionnaire was developed to measure the effect of general health and symptom severity on work productivity and regular activities in the 7 days prior to the visit. The WPAI-AD consists of 6 items grouped in 4 domains: absenteeism (work time missed), presenteeism (impairment at work/reduced on-the-job effectiveness), work productivity loss (overall work impairment/absenteeism plus presenteeism), and activity impairment, that range from 0% to 100%, with higher values indicating greater impairment.
LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.Change From Baseline on the EQ-5D-5L Visual Analog Scale (VAS) Baseline, Week 16 The EQ-5D-5L is a 2-part measurement. The second part is assessed using a VAS that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine.
LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.Mean Number of Days Without Use of Background TCS Week 0 through Week 16 The ANCOVA model includes treatment, region, and baseline disease severity (IGA) as factors.
Percentage of Participants Achieving IGA of 0 or 1 With a ≥ 2 Point Improvement Week 4 The IGA measures the investigator's global assessment of the participant's overall severity of their AD, based on a static, numeric 5-point scale from 0 (clear skin) to 4 (severe disease). The score is based on an overall assessment of the degree of erythema, papulation/induration, oozing/crusting, and lichenification.
Change From Baseline on the Dermatology Life Quality Index (DLQI) Baseline, Week 16 The DLQI is a simple, participant-administered,10 question, validated, quality-of-life questionnaire that covers 6 domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. The recall period of this scale is over the last "week." Response categories include "not at all," "a lot," and "very much," with corresponding scores of 1, 2, and 3, respectively, and at unanswered ("not relevant") responses scored as "0." Scores range from 0 to 30 (less to more impairment), and a 4-point change from baseline is considered as the minimal clinically important difference threshold.
LS Means were calculated using MMRM model with treatment, region, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interaction as fixed continuous effects.
Trial Locations
- Locations (68)
Charité Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Kawashima Dermatology Clinic
🇯🇵Ichikawa-shi, Chiba, Japan
Yamano Dermatological Clinic
🇯🇵Dazaifu, Fukuoka, Japan
Centro de Investigaciones Metabólicas (CINME) - Comite
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Shibaki Dermatology Clinic
🇯🇵Sapporo, Hokkaido, Japan
Woden Dermatology
🇦🇺Phillip, Australian Capital Territory, Australia
Skin & Cancer Foundation Australia
🇦🇺Westmead, New South Wales, Australia
The Skin Centre
🇦🇺Benowa, Queensland, Australia
Instituto de Neumonología y Dermatología
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Parra Dermatología
🇦🇷Mendoza, Argentina
Hosono Clinic
🇯🇵Chuo-ku, Tokyo, Japan
Fremantle Dermatology
🇦🇺Perth, Western Australia, Australia
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Konkuk University Hospital
🇰🇷Seoul, Korea, Republic of
JA Shizuoka Kohseiren Enshu Hospital
🇯🇵Hamamatsu-shi, Shizuoka, Japan
Fundacion CIDEA
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Psoriahue Medicina Interdisciplinaria
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Sapporo Skin Clinic
🇯🇵Sapporo, Hokkaido, Japan
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Baden-Württemberg, Germany
Yoshioka Dermatology Clinic
🇯🇵Neyagawa-shi, Osaka, Japan
Queen's Square Dermatology and Allergology
🇯🇵Nishi-ku, Yokohama-city, Kanagawa, Japan
ULSS 8 UOC Dermatologia Viale Rodolfi, 37
🇮🇹Vicenza, Italy
Tashiro Dermatological Clinic
🇯🇵Iizuka-city, Fukuoka, Japan
Senri-Chuo Hanafusa Dermatology Clinic
🇯🇵Toyonaka-shi, Osaka, Japan
Shirasaki Clinic
🇯🇵Takaoka-shi, Toyama, Japan
Yamate Dermatological Clinic
🇯🇵Shinjuku, Tokyo, Japan
Tachikawa Dermatology Clinic
🇯🇵Tachikawa-shi, Tokyo, Japan
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Korea, Republic of
Chang Gung Memorial Hospital - Kaohsiung
🇨🇳Kaohsiung, Taiwan
Chung Shan Medical University Hospital
🇨🇳Taichung City, Taiwan
Chang Gung Memorial Hospital - Taipei
🇨🇳Taipei, Taiwan
Universitätsklinikum Schleswig-Holstein
🇩🇪Lübeck, Schleswig-Holstein, Germany
Tokyo Teishin Hospital
🇯🇵Chiyoda-Ku, Tokyo, Japan
Istituto Clinico Humanitas
🇮🇹Rozzano, Milano, Italy
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Universitätsklinikum Aachen - UKA
🇩🇪Aachen, Nordrhein-Westfalen, Germany
Universitaetsklinikum Essen
🇩🇪Essen, Nordrhein-Westfalen, Germany
Skin and Cancer Foundation Inc.
🇦🇺Melbourne, Victoria, Australia
Clinical Trials SA Pty Ltd
🇦🇺Adelaide, South Australia, Australia
Oizumi Hanawa Clinic
🇯🇵Nerima-ku, Tokyo, Japan
Veracity Clinical Research Pty Ltd
🇦🇺Woolloongabba, Queensland, Australia
Universitätsklinikum Graz
🇦🇹Graz, Steiermark, Austria
Klinikum der Universität München
🇩🇪München, Bayern, Germany
Rosenpark Research Geschäftsbereich der Rosenparkklinik GmbH
🇩🇪Darmstadt, Hessen, Germany
Policlinico Univ. Agostino Gemelli
🇮🇹Roma, Lazio, Italy
TFS Trial Form Support GmbH
🇩🇪Hamburg, Germany
Medical Corporation Soleil Miyata Dermatology Clinic
🇯🇵Matsudo-shi, Chiba, Japan
Azienda Ospedaliera Universitaria Ospedale San Martino di Genova
🇮🇹Genova, Italy
Azienda Ospedaliera - Universitaria Pisana
🇮🇹Pisa, Italy
Iidabashi Clinic
🇯🇵Chiyoda-ku, Tokyo, Japan
Korea University Ansan Hospital
🇰🇷Ansan-si, Gyeonggi-do, Korea, Republic of
Hallym University Kangnam Sacred Heart Hospital
🇰🇷Seoul, Korea, Republic of
Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Chungang University Hospital
🇰🇷Seoul, Korea, Republic of
Dongguk University Ilsan Hospital
🇰🇷Goyang, Gyeonggi-do, Korea, Republic of
Lubelskie Centrum Diagnostyczne
🇵🇱Swidnik, Poland
Centrum Medyczne Evimed
🇵🇱Warszawa, Poland
Hospital Reina Sofia
🇪🇸Cordoba, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital De Gran Canaria Dr. Negrin
🇪🇸Las Palmas de Gran Canaria, Spain
Dermatologisches Zentrum Osnabrück Nord
🇩🇪Bramsche, Niedersachsen, Germany
Universitätsklinikum Münster
🇩🇪Münster, Nordrhein-Westfalen, Germany
Hospital del Mar
🇪🇸Barcelona, Spain
Dermed Centrum Medyczne Sp. z o.o.
🇵🇱Lodz, Poland
Taipei Medical University- Shuang Ho Hospital
🇨🇳New Taipei City, Taiwan
Centrum Medyczne AMED
🇵🇱Warszawa, Poland
National Taiwan University Hospital
🇨🇳Taipei City, Taiwan
Chang Gung Memorial Hospital - Linkou
🇨🇳Taoyuan, (r.o.c.), Taiwan