Tralokinumab Monotherapy for Moderate to Severe Atopic Dermatitis - ECZTRA 1 (ECZema TRAlokinumab Trial no. 1)
- Registration Number
- NCT03131648
- Lead Sponsor
- LEO Pharma
- Brief Summary
Primary objective:
To evaluate the efficacy of tralokinumab compared with placebo in treating moderate to severe atopic dermatitis (AD).
Secondary objectives:
To evaluate the efficacy of tralokinumab on severity and extent of AD, itch, and health related quality of life compared with placebo.
Maintenance objective:
To evaluate maintenance of effect with continued tralokinumab dosing up to 52 weeks compared to placebo for subjects achieving clinical response at Week 16.
- Detailed Description
Subjects found eligible following the screening period were randomized 3:1 to initial treatment with tralokinumab 300 mg every 2 weeks (Q2W) or placebo. Randomization was stratified by region (North America, Europe, and Japan) and disease severity (Investigator's Global Assessment \[IGA\] 3 or 4).
Subjects achieving a clinical response at Week 16 (defined as IGA of 0 or 1 on a 5-point scale ranging from 0 \[clear\] to 4 \[severe\], or at least 75% reduction in Eczema Area and Severity Index \[EASI\] score from baseline \[EASI75\]) continued into maintenance treatment that continued until Week 52.
Subjects randomized to tralokinumab in the initial treatment period and who achieved a clinical response at Week 16 (defined by IGA 0 or 1, or EASI75) were re-randomized 2:2:1 to one of the following Q2W maintenance regimens stratified by region (North America, Europe, and Japan) and IGA response at Week 16 (IGA 0/1 or IGA \>1):
* Tralokinumab 300 mg Q2W.
* Tralokinumab 300 mg Q4W (alternating dose administrations tralokinumab 300 mg and placebo).
* Placebo (Subjects randomized to placebo in the initial treatment period who achieved a clinical response at Week 16 \[defined by IGA 0 or 1, or EASI75\] continued to receive placebo Q2W in the maintenance treatment period).
Subjects not achieving a clinical response at Week 16 as well as those who met the criteria listed below during maintenance treatment were transferred to open-label tralokinumab 300 mg Q2W treatment with optional use of topical corticosteroid (TCS) up to Week 52.
Transfer to open-label treatment during maintenance:
Subjects with IGA=0 at Week 16: IGA of at least 2 and not achieved EASI75 over at least a 4-week period (i.e. over 3 consecutive visits).
Subjects with IGA=1 at Week 16: IGA of at least 3 and not achieved EASI75 over at least a 4-week period (i.e. over 3 consecutive visits).
Subjects with IGA \>1 at Week 16: not achieved EASI75 over at least a 4-week period (i.e. over 3 consecutive visits).
Subjects transferring to open-label treatment had the option to self-administer tralokinumab in their home after adequate training (at 3 dosing visits in the open-label period after additional consent has been obtained) by site staff at the investigator's discretion.
After completion of the maintenance treatment period (or open-label treatment), all subjects, except for those who entered the open-label long-term extension trial, continued in a 14-week off-treatment follow-up period for the assessment of safety and anti-drug antibody (ADA).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 802
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Written informed consent and any locally required authorisation obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
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Age 18 and above.
-
Diagnosis of AD as defined by the Hanifin and Rajka (1980) criteria for AD (34; Appendix 5).
-
Diagnosis of AD for ≥1 year.
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Subjects who have a recent history (within 1 year before the screening visit) of inadequate response to treatment with topical medications or for whom topical treatments are otherwise medically inadvisable (e.g., due to important side effects or safety risks).
Inadequate response is defined as failure to achieve and maintain remission or a low disease activity state (comparable to IGA 0=clear to 2=mild) despite treatment with a daily regimen of TCS of medium to higher potency (±TCI as appropriate), applied for at least 28 days or for the maximum duration recommended by the product prescribing information (e.g., 14 days for super potent TCS), whichever is shorter.
Subjects with documented systemic treatment for AD in the past year are also considered as inadequate responders to topical treatments and are potentially eligible for treatment with tralokinumab after appropriate washout.
Important side effects or safety risks are those that outweigh the potential treatment benefits and include intolerance to treatment, hypersensitivity reactions, significant skin atrophy, and systemic effects, as assessed by the investigator or by the subject's treating physician.
-
AD involvement of ≥10% body surface area at screening and baseline (visit 3).
-
An EASI score of ≥12 at screening and 16 at baseline.
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An IGA score of ≥3 at screening and at baseline.
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A Worst Daily Pruritus numeric rating scale (NRS) average score of ≥4 during the week prior to baseline.
Worst Daily Pruritus NRS at baseline will be calculated from daily assessments of worst itch severity (Worst Daily Pruritus NRS) during the 7 days immediately preceding randomisation (Day 6 to 0). A minimum of 4 Worst Daily Pruritus NRS scores out of the 7 days is required to calculate the baseline average score. For subjects who do not have at least 4 scores reported during the 7 days immediately preceding the planned randomisation date, randomisation should be postponed until this requirement is met, but without exceeding the 6 weeks maximum duration for screening.
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Subjects must have applied a stable dose of emollient twice daily (or more, as needed) for at least 14 days before randomisation (refer to exclusion criterion no. 8 for limitations regarding emollients).
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Women of childbearing potential must use a highly effective* form of birth control (confirmed by the investigator) throughout the trial and at least for 16 weeks (5 half lives) after last administration of IMP.
- A highly effective method of birth control is defined as one which results in a low failure rate (less than 1% per year) such as bilateral tubal occlusion, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), sexual abstinence (when this is in line with the preferred and usual life style of the subject), vasectomised partner (given that the subject is monogamous). The subjects must have used the contraceptive method continuously for at least 1 month prior to the pregnancy test at baseline. A female is defined as not being of child-bearing potential if she is postmenopausal (at least 12 months with no menses without an alternative medical cause prior to screening), or surgically sterile (hysterectomy, bilateral salpingectomy or bilateral oophorectomy).
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Concurrent enrolment in another clinical trial where the subject is receiving an IMP.
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Previous randomisation in tralokinumab trials.
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Active dermatologic conditions that may confound the diagnosis of AD or would interfere with assessment of treatment, such as scabies, cutaneous lymphoma, or psoriasis.
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Known active allergic or irritant contact dermatitis that is likely to interfere with the assessment of severity of AD.
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Use of tanning beds or phototherapy (narrow band ultraviolet B [NBUVB], ultraviolet B [UVB], ultraviolet A1 [UVA1], psoralen + ultraviolet A [PUVA]), within 6 weeks prior to randomisation.
-
Treatment with the following medications within 4 weeks prior to randomisation:
- Systemic immunosuppressive/immunomodulating drugs (e.g. methotrexate, cyclosporine, azathioprine, mycophenolate mofetil, Janus kinase inhibitors etc.).
- Systemic corticosteroid use (excludes topical, inhaled, or intranasal delivery).
- Three or more bleach baths during any week within the 4 weeks.
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Treatment with the following medications within 2 weeks prior to randomisation
- TCS.
- TCI.
- Topical PDE 4 inhibitor.
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Initiation of treatment of AD with prescription emollients or emollients containing additives such as ceramide, hyaluronic acid, urea, or filaggrin degradation products during the screening period (subjects may continue using stable doses of such emollients if initiated before the screening visit).
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Receipt of live attenuated vaccines 30 days prior to the date of randomisation and during the trial including the safety follow-up period.
• Receipt of inactive/killed vaccinations (e.g. inactive influenza) are allowed, provided they are not administered within 5 days before/after any study visit.
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Receipt of any marketed (i.e. immunoglobulin, anti-IgE) or investigational biologic agent, including dupilumab:
- Any cell-depleting agents including but not limited to rituximab: within 6 months prior to randomisation, or until lymphocyte count returns to normal, whichever is longer.
- Other biologics: within 3 months or 5 half-lives, whichever is longer, prior to randomisation.
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Receipt of any investigational non-biologic agent within 5 half-lives prior to randomisation.
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Receipt of blood products within 4 weeks prior to screening.
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Major surgery within 8 weeks prior to screening, or planned in-patient surgery or hospitalisation during the trial period.
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Known or suspected allergy or reaction to any component of the IMP formulation.
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History of any active skin infection within 1 week prior to randomisation.
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History of a clinically significant infection within 4 weeks prior to randomisation which, in the opinion of the investigator or sponsor's medical expert, may compromise the safety of the subject in the trial, interfere with evaluation of the IMP, or reduce the subject's ability to participate in the trial. Clinically significant infections are defined as:
- a systemic infection.
- a serious skin infection requiring parenteral (intravenous or intramuscular) antibiotics, antiviral, or antifungal medication.
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A helminth parasitic infection within 6 months prior to the date informed consent is obtained that has not been treated with, or has failed to respond to, standard of care therapy.
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History of anaphylaxis following any biologic therapy.
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History of immune complex disease.
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History of cancer:
- Subjects who have had basal cell carcinoma, localised squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible provided that the subject is in remission and curative therapy was completed at least 12 months prior to the date informed consent was obtained.
- Subjects who have had other malignancies are eligible provided that the subject is in remission and curative therapy was completed at least 5 years prior to the date informed consent was obtained.
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Tuberculosis requiring treatment within the 12 months prior to screening. Evaluation will be according to local guidelines as per local standard of care.
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History of any known primary immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test at screening, or the subject taking antiretroviral medications as determined by medical history and/or subject's verbal report.
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History of chronic alcohol or drug abuse within 12 months prior to screening, or any condition associated with poor compliance as judged by the investigator.
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History of attempted suicide or is at significant risk of suicide (either in the opinion of the investigator or defined as a "yes" to suicidal ideation questions no. 4 or 5 or answering "yes" to suicidal behaviour on the Columbia-Suicide Severity Rating Scale [C-SSRS] Screening version).
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Any disorder, including but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, immunological, psychiatric, or major physical impairment that is not stable, in the opinion of the investigator, and could:
- Affect the safety of the subject throughout the trial.
- Influence the findings of the trial or their interpretations.
- Impede the subject's ability to complete the entire duration of trial.
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Any clinically significant abnormal findings in physical examination, vital signs, electrocardiogram (ECG), haematology, clinical chemistry, or urinalysis during the screening period, which in the opinion of the investigator, may put the subject at risk because of his/her participation in the trial, or may influence the results of the trial, or the subject's ability to complete entire duration of the trial.
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Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.0 times the ULN (upper limit of normal) at screening.
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Positive hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B core antibody (HBcAb) or hepatitis C virus antibody (anti-HCV) serology at screening. Subjects with positive HBsAb may be randomised provided they are hepatitis B vaccinated and have negative HBsAg and HBcAb.
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Subjects who are not willing to abstain from donating blood and/or plasma from the time of informed consent and for 16 weeks (5 half-lives) after last dose of IMP.
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Subjects who are legally institutionalised.
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Pregnant, breastfeeding, or lactating women.
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Employees of the trial site or any other individuals directly involved with the planning or conduct of the trial, or immediate family members of such individuals.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Maintenance treatment period - Tralokinumab Q2W Tralokinumab Week 16 to Week 52: Tralokinumab responders from the initial treatment period re-randomised at Week 16 and administered tralokinumab maintenance subcutaneous injection regimen Q2W for 36 weeks. Initial treatment period - Placebo Q2W Placebo Week 0 to Week 16: Two subcutaneous (SC) injections of placebo as a loading dose on Day 0 followed by a SC injection of placebo Q2W regimen for 16 weeks. Maintenance treatment period - Tralokinumab Q4W Tralokinumab Week 16 to Week 52: Tralokinumab responders from the initial treatment period re-randomised at Week 16 and administered tralokinumab maintenance subcutaneous injection regimen Q4W for 36 weeks. Subjects in this group receive alternating doses of tralokinumab SC injection and placebo SC injection every 2 weeks. Maintenance treatment period - Tralokinumab Q4W Placebo Week 16 to Week 52: Tralokinumab responders from the initial treatment period re-randomised at Week 16 and administered tralokinumab maintenance subcutaneous injection regimen Q4W for 36 weeks. Subjects in this group receive alternating doses of tralokinumab SC injection and placebo SC injection every 2 weeks. Maintenance treatment period - Placebo Q2W Placebo Week 16 to Week 52: Tralokinumab responders from initial treatment period randomised at Week 16 and administered placebo subcutaneous maintenance injection for 36 weeks. Maintenance treatment period - Placebo Placebo Week 16 to Week 52: Placebo responders from the initial treatment period re-assigned at Week 16 and administered placebo maintenance subcutaneous injection regimen Q2W for 36 weeks. Open-label treatment - Tralokinumab + optional TCS Tralokinumab Week 16 to Week 52: Subjects receiving initial treatment with tralokinumab Q2W or placebo Q2W assigned to open-label treatment at Week 16 and administered Tralokinumab subcutaneous (SC) injection + optional TCS\* regimen Q2W. OR Subjects receiving maintenance treatment with tralokinumab Q2W/Q4W or placebo assigned to open-label treatment after Week 16 and administered tralokinumab SC injection + optional TCS\* regimen Q2W. \*TCS = topical corticosteroids. Initial treatment period - Tralokinumab Q2W Tralokinumab Week 0 to Week 16: Two subcutaneous (SC) injections of tralokinumab as a loading dose on Day 0, followed by a SC injection of tralokinumab Q2W regimen for 16 weeks. Open-label short-term- Tralokinumab + optional TCS Tralokinumab Week 52 to Week 68 \[Short term extension (Japan only)\] : Japanese subjects who were transferred to the open-label tralokinumab Q2W arm at Week 16 continued an additional 16 weeks (Week 52 to Week 66) of open-label treatment to receive 52 weeks of active therapy.
- Primary Outcome Measures
Name Time Method Subjects Achieving at Least 75% Reduction in Eczema Area and Severity Index [EASI] at Week 16 At Week 16 The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition.
Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16 At Week 16 The IGA is an instrument used in clinical trials to rate the severity of the subject's global AD and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).
- Secondary Outcome Measures
Name Time Method Reduction of Worst Daily Pruritus Numeric Rating Scale (Weekly Average) of at Least 4 From Baseline to Week 16. Week 0 to Week 16 Subjects will assess their worst itch severity over the past 24 hours using an 11 point NRS ('Worst Daily Pruritus NRS') with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'.
Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 52 Among Subjects With IGA of 0/1 at Week 16 At Week 52 The IGA is an instrument used in clinical trials to rate the severity of the subject's global AD and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).
Subjects With at Least 75% Reduction in Eczema Area and Severity Index [EASI] at Week 52 Among Subjects With EASI75 at Week 16 At Week 52 The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition.
Safety and Tolerability: Adverse Event (AE) /Serious Adverse Event (SAE) Frequency Week 0 to Week 16 Overall summary of AEs and SAEs during the Initial treatment period is presented. For list of AEs and SAEs by MedDRA system organ class (SOC) and preferred term (PT) during the entire trial period (including safety follow-up), see Adverse Events Overview section.
Frequency of Anti-drug Antibodies Week 0 to Week 16 Anti-tralokinumab antibody levels were analysed using a validated bioanalytical method.
Subjects Achieving at Least 50% Reduction in Eczema Area and Severity Index [EASI] at Week 16 At Week 16 The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition.
Change From Baseline to Week 16 in Eczema Area and Severity Index [EASI] Score Week 0 to Week 16 The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition.
Subjects Achieving at Least 90% Reduction in Eczema Area and Severity Index [EASI] at Week 16 At Week 16 The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition.
Change in Scoring Atopic Dermatitis (SCORAD) From Baseline to Week 16 Week 0 to Week 16 The SCORAD is a validated tool to evaluate the extent and severity of atopic dermatitis lesions, along with subjective symptoms. The score ranges from 0 to 103, with higher values indicating a more extensive and/or severe condition.
Change in Dermatology Life Quality Index (DLQI) Score From Baseline to Week 16 Week 0 to Week 16 The Dermatology Life Quality Index (DLQI) is a validated questionnaire with content specific to those with dermatology conditions. It consists of 10 items addressing the subject's perception of the impact of their skin disease on different aspects of their quality of life (QoL) over the last week such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4 point Likert scale (0 = not at all ⁄not relevant; 1 = a little; 2 = a lot; 3 = very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor QoL.
Subjects Achieving at Least 75% Reduction in Scoring Atopic Dermatitis (SCORAD) at Week 16 At Week 16 The SCORAD is a validated tool to evaluate the extent and severity of atopic dermatitis lesions, along with subjective symptoms. The score ranges from 0 to 103, with a higher values indicating a more extensive and/or severe condition.
Subjects Achieving at Least 50% Reduction in Scoring Atopic Dermatitis (SCORAD) at Week 16 At Week 16 The SCORAD is a validated tool to evaluate the extent and severity of atopic dermatitis lesions, along with subjective symptoms. The score ranges from 0 to 103, with higher values indicating a more extensive and/or severe condition.
Change From Baseline to Week 16 in Worst Daily Pruritus NRS (Weekly Average) Week 0 to Week 16 Subjects will assess their worst itch severity over the past 24 hours using an 11 point NRS ('Worst Daily Pruritus NRS') with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'
Reduction of Worst Daily Pruritus NRS (Weekly Average) ≥3 From Baseline to Week 16 Week 0 to Week 16 Subjects will assess their worst itch severity over the past 24 hours using an 11 point NRS ('Worst Daily Pruritus NRS') with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'.
Reduction From Baseline to Week 16 of Dermatology Life Quality Index (DLQI) of ≥4 Points Among Subjects With Baseline DLQI ≥4 Week 0 to Week 16 The DLQI is a validated questionnaire with content specific to those with dermatology conditions. It consists of 10 items addressing the subject's perception of the impact of their skin disease on different aspects of their QoL over the last week such as dermatology related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4 point Likert scale (0 = not at all/not relevant; 1 = a little; 2 = a lot; 3 = very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor QoL.
Trial Locations
- Locations (123)
Dermatology Research Associates
🇺🇸Los Angeles, California, United States
PMG Research of Christie Clinic
🇺🇸Chicago, Illinois, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Dermatology Associates of Seattle
🇺🇸Seattle, Washington, United States
Houston Skin Associates
🇺🇸Houston, Texas, United States
Dermatology Specialists, Inc.
🇺🇸Oceanside, California, United States
Center for Clinical Studies
🇺🇸Webster, Texas, United States
Tekton Research
🇺🇸Austin, Texas, United States
Dermtology Treatment and Research Center
🇺🇸Dallas, Texas, United States
CHU de Dijon, Service de Dermatologie
🇫🇷Dijon, France
GHRMSA, Service de Dermatologie
🇫🇷Mulhouse, France
Jichi Medical University Hospital
🇯🇵Tochigi, Japan
Nippon Medical School Hospital
🇯🇵Tokyo, Japan
Hôpital de l'Archet II, Service de Dermatologie- Vénérologie
🇫🇷Nice, France
Hôpital Robert Debré, Service de Dermatologie
🇫🇷Reims, France
Clinical Trials of SWLA, LLC
🇺🇸Lake Charles, Louisiana, United States
Hôpital St ANDRE, CHU de BORDEAUX, Service de Dermatologie
🇫🇷Bordeaux, France
Cabinet Médical, Le Bateau Blanc-Immeuble A
🇫🇷Martigues, France
UPMC Department of Dermatology
🇺🇸Pittsburgh, Pennsylvania, United States
Dermatologists of Greater Columbus
🇺🇸Bexley, Ohio, United States
Centre Hospitalier Universitaire, Clinique dermatologique 7 eme nord
🇫🇷Nantes, France
Hôpital Saint vincent de paul, Clinique de Dermatologie
🇫🇷Lille Cedex, France
Virginia Clinical Research
🇺🇸Norfolk, Virginia, United States
CHRU de Brest - Hôpital Morvan, Service de Dermatologie
🇫🇷Brest Cedex, France
Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Dermatologie
🇩🇪Dresden, Saxony, Germany
Hôpital Claude Huriez-CHRU, Service de dermatologie
🇫🇷Lille, France
Osaka Habikono Medical Center
🇯🇵Habikino, Japan
Charité - Universitätsmedizin Berlin, Klinik für Dermatologie, Allergologie und Venerologie
🇩🇪Berlin, Germany
Universitätsklinikum Leipzig, Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
🇩🇪Leipzig, Saxony, Germany
CMB Collegium Medicum Berlin GmbH
🇩🇪Berlin, Germany
JR Sapporo Hospital
🇯🇵Chūō, Japan
Klinikum Darmstadt GmbH, Hautklinik
🇩🇪Darmstadt, Hessia, Germany
Asahikawa City Hospital
🇯🇵Asahikawa, Japan
Fukuoka University Hospital
🇯🇵Fukuoka, Japan
Niesmann, Hautzentrum im Jahrhunderthaus
🇩🇪Bochum, NRW, Germany
Hyogo College Of Medicine Hospital
🇯🇵Hyōgo, Nishinomiya, Japan
NTT Medical Center Tokyo
🇯🇵Tokyo, Shinagawa, Japan
Tokyo Medical University Hospital
🇯🇵Tokyo, Japan
Hôpital Charles Nicolle, Clinique Dermatologique
🇫🇷Rouen, France
Gifu University Hospital
🇯🇵Gifu-shi, Japan
The Jikei University Hospital
🇯🇵Tokyo, Japan
Kurume University Hospital
🇯🇵Fukuoka, Japan
Hautzentrum Dülmen
🇩🇪Dülmen, NRW, Germany
Hospital Clinic de Barcelona, Dermatology Department
🇪🇸Barcelona, Catalunya, Spain
Hospital Infanta Leonor, Servicio Dermatología
🇪🇸Madrid, Spain
Hospital de Cruces, Servicio Dermatología
🇪🇸Bilbao, País Vasco, Spain
Hospital Universitario y Politécnico La Fe, Servicio Dermatología
🇪🇸Valencia, Spain
Hospital de la Santa Creu i Sant Pau, Servicio Dermatología
🇪🇸Barcelona, Catalunya, Spain
Hospital de Fuenlabrada, Servicio Dermatología
🇪🇸Madrid, Spain
Hospital del Mar, Servicio Dermatología
🇪🇸Barcelona, Catalunya, Spain
Hamamatsu University hospital
🇯🇵Hamamatsu, Japan
Kyoto Prefectural Hospital
🇯🇵Kyoto, Japan
Fukushima Medical University Hospital
🇯🇵Fukushima, Japan
Ichinomiya Municipal Hospital
🇯🇵Ichinomiya, Japan
Hospital de Basurto, Servicio Dermatología
🇪🇸Bilbao, País Vasco, Spain
Hospital Germans Trias i Pujol, Servicio Dermatología
🇪🇸Badalona, Catalunya, Spain
Hospital Virgen de la Macarena, Servicio Dermatología
🇪🇸Sevilla, Andalucía, Spain
Hospital Universitario La Paz, Servicio Dermatología
🇪🇸Madrid, Spain
University Clinical Trials, Inc.
🇺🇸San Diego, California, United States
Facharztpraxis für Dermatologie, Allergologie, Venerologie und Umweltmedizin
🇩🇪Mahlow, Brandenburg, Germany
Derma-Study-Center Friedrichshafen GmbH
🇩🇪Friedrichshafen, Baden-Württemberg, Germany
Hautärzte Zentrum Hannover
🇩🇪Hannöver, Lower Saxony, Germany
Universitätsklinikum Halle (Saale), Universitätsklinik und Poliklinik für Dermatologie und Venerologie
🇩🇪Halle (Saale), Saxony-Anhalt, Germany
Klinikum Augsburg, Klinik für Dermatologie und Allergologie
🇩🇪Augsburg, Bavaria, Germany
Universitätsklinikum Erlangen, Hautklinik
🇩🇪Erlangen, Bavaria, Germany
SRH Wald-Klinikum Gera, Klinik für klinische Studien
🇩🇪Gera, Thuringia, Germany
Medizinische Hochschule Hannover, Klinik für Dermatologie, Allergologie und Venerologie
🇩🇪Hannöver, Lower Saxony, Germany
Clinical Research Center of Alabama
🇺🇸Birmingham, Alabama, United States
Oregon Medical Research Center
🇺🇸Portland, Oregon, United States
Oregon Health & Sciences University
🇺🇸Portland, Oregon, United States
SCIderm GmbH
🇩🇪Hamburg, Germany
LMU München, Klinik und Poliklinik für Dermatologie und Allergologie
🇩🇪München, Bavaria, Germany
Tien Q. Nguyen, MD, Inc.
🇺🇸Fountain Valley, California, United States
Quest Dermatology Research
🇺🇸Northridge, California, United States
Skin Care Research, Inc.
🇺🇸Boca Raton, Florida, United States
The GWU Medical Faculty Associates
🇺🇸Washington, District of Columbia, United States
Allergy Center at Brookstone Research
🇺🇸Columbus, Georgia, United States
Georgia Pollens Clinical Research Centers, Inc.
🇺🇸Albany, Georgia, United States
Park Avenue Dermatology
🇺🇸Orange Park, Florida, United States
Research Institute of the Southeast, LLC
🇺🇸West Palm Beach, Florida, United States
ACRC Dermatology
🇺🇸West Palm Beach, Florida, United States
Altman Dermatology Associates
🇺🇸Arlington Heights, Illinois, United States
Dermatologic Surgery Specialists
🇺🇸Macon, Georgia, United States
Meridian Clinical Research
🇺🇸Savannah, Georgia, United States
Deaconess Clinic
🇺🇸Evansville, Indiana, United States
DermAssociates, PC
🇺🇸Rockville, Maryland, United States
Clarkston Skin Research
🇺🇸Clarkston, Michigan, United States
University at Buffalo Department of Dermatology
🇺🇸Buffalo, New York, United States
JDR Dermatology Research
🇺🇸Las Vegas, Nevada, United States
Derm Center
🇺🇸Troy, Michigan, United States
MediSearch LLC
🇺🇸Saint Joseph, Missouri, United States
Juva Skin & Laser Center
🇺🇸New York, New York, United States
Weil Cornell Medicine
🇺🇸New York, New York, United States
Deramatology Consulting Services, PLLC
🇺🇸High Point, North Carolina, United States
Centre Hospitalier de Valence
🇫🇷Valence, Drôme, France
West Virginia Research Institute
🇺🇸Morgantown, West Virginia, United States
CHU de Toulouse Hôpital Larrey, Service de Dermatologie
🇫🇷Toulouse, France
C.H.U. de Saint-Etienne - Hôpital Nord, Service de dermatologie
🇫🇷Saint-Etienne Cedex 2, France
KliFOs - Klinische Forschung Osnabrück
🇩🇪Osnabrück, Lower Saxony, Germany
Klinikum Bielefeld Rosenhöhe, Hautklinik
🇩🇪Bielefeld, NRW, Germany
Universitätsklinikum Bonn, Klinik und Poliklinik für Dermatologie und Allergologie
🇩🇪Bonn, NRW, Germany
Universitätsklinikum Essen (AöR), Klinik für Dermatologie, Venerologie und Allergologie
🇩🇪Essen, NRW, Germany
Universitätsklinikum Münster Klinik und Poliklinik für Hautkrankheiten Münster, Zentrale Studienkoordination für innovative Dermatologie
🇩🇪Münster, NRW, Germany
KUME Clinic
🇯🇵Sakai City, Osaka, Japan
Meiwa Hospital
🇯🇵Hyōgo, Nishinomiya, Japan
Medical Corporation Kojinkai
🇯🇵Chūō, Japan
Shirasaki Dermatology Clinic
🇯🇵Tōyama, Japan
Kagoshima University Hospital
🇯🇵Kagoshima, Japan
Tokyo Teishin Hospital
🇯🇵Tokyo, Japan
Chukyo Hospital
🇯🇵Nagoya, Japan
Takagi Dermatological Clinic
🇯🇵Obihiro, Japan
Iwate Prefectural Central Hospital
🇯🇵Morioka, Japan
The Fraternity Memorial Hospital
🇯🇵Tokyo, Japan
Gokeikai Osaka Kaisei Hospital
🇯🇵Ōsaka, Japan
Ogikubo Hospital
🇯🇵Tokyo, Japan
Osaka Hospital
🇯🇵Ōsaka, Japan
Hospital Universitario de la Princesa, Servicio Dermatología
🇪🇸Madrid, Spain
Hospital Reina Sofía, Servicio Dermatología
🇪🇸Córdoba, Andalucía, Spain
Center for Dermatology and Laser Surgery
🇺🇸Sacramento, California, United States
Skin Sciences, PLLC
🇺🇸Louisville, Kentucky, United States
Forward Clinical Trials
🇺🇸Tampa, Florida, United States
Austin Dermatology Associates
🇺🇸Austin, Texas, United States
Clínica Universitaria de Navarra, Servicio Dermatología
🇪🇸Pamplona, Navarra, Spain