A Study of Crisaborole Ointment 2%; Crisaborole Vehicle; TCS and TCI in Subjects Aged ≥ 2 Years, With Mild-moderate AD
- Conditions
- Atopic Dermatitis
- Interventions
- Registration Number
- NCT03539601
- Lead Sponsor
- Pfizer
- Brief Summary
This 4-week study will evaluate the safety and efficacy of crisaborole ointment 2%; crisaborole vehicle; topical corticosteroid and topical calcineurin inhibitor, applied twice daily (BID) in subjects who are at least 2 years of age with mild-moderate AD.
A Sub-Study of Optical Coherence Tomography and Biomarkers in Subjects ages 2 to \<18 years old, with Mild to Moderate Atopic Dermatitis, treated with Crisaborole Ointment, 2% or Crisaborole Vehicle Ointment or Hydrocortisone Butyrate 0.1% Cream applied BID will also be conducted at select sites.
- Detailed Description
Approximately 600 subjects will be enrolled in the study, of which at least 150 subjects aged 2-6; at least 140 subjects aged 7-11; at least 120 subjects aged 12-17 and up to 90 subjects will be adults. Subjects must have mild-moderate AD involving at least 5% treatable %BSA assessed on baseline/Day 1. Treatable %BSA will be defined as the percent of a subject's total body surface area that is AD involved, excluding the scalp.
Eligible subjects will be randomized at the Baseline/Day 1 visit. Randomization will be stratified by eligibility for TCS or TCI treatment as per national approved labels. Cohort 1 will be for subjects who are eligible for TCS therapy, and Cohort 2 will be for subjects who are not eligible for TCS therapy but eligible for TCI therapy. The investigational products will be applied BID for 28 days to the Treatable body surface area (BSA) identified at Baseline/Day 1.
The primary efficacy endpoint is the percent change from baseline in the Eczema Area and Severity Index (EASI) total score at Day 29.
For the efficacy comparison of crisaborole versus vehicle, subjects from both Cohort 1 and Cohort 2 are included in the analysis, adjusted for cohort effect. For the efficacy comparison of crisaborole versus TCS, only subjects from Cohort 1 are included in the analysis. For the comparison of crisaborole versus TCI, only subjects from Cohort 2 are included in the analysis.
Safety and efficacy assessments will be conducted at the investigator site by a clinical assessor blinded to treatment assignment.
Scheduled study visits for all subjects will occur at Screening, Baseline/Day 1, Day 8, Day 15, Day 22, Day 29 (End of treatment/Early termination), Day 43 or 14 Days after last dose if subject is terminated early from treatment. A follow up telephone call will be made by site staff to the subjects/subject's legally acceptable guardian(s) on Day 60 or at least 28 days after last dose if subject is terminated early from treatment. The Day 60 visit will be completed in the clinic for subjects enrolled in the OCT sub-study.
To further explore the benefit/risk of crisaborole ointment, 2%, a sub-study to evaluate differences in atrophic skin changes across study treatment groups in Cohort 1 will be conducted at select sites.
The sub-study will include obtaining Optical coherence tomography (OCT) imaging to evaluate atrophic changes in epidermal thickness during and after treatment with study investigational product in Cohort 1. This sub-study also provides an opportunity to explore differences in Transepidermal Water Loss (TEWL) and cutaneous inflammatory and barrier biomarkers associated with AD within the stratum corneum (SC) across treatment groups in Cohort 1. The Aquaflux (an evaporimeter) will be used in this sub-study to evaluate TEWL during and after treatment at select sub-study centers. Tape-strips will also be used in this sub-study to evaluate SC biomarkers from AD lesional and non-lesional skin.
This sub-study will include approximately 60 subjects from Cohort 1 that are enrolled in the main study (C3291037). Subjects will follow the main study assessments and visits as per the schedule of activities for the main study but will also follow additional procedures as described in the protocol. The telephone call at Day 60 in the main study is replaced with an in-clinic visit for sub-study participants.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 237
Is male or female 2 years and older at the Screening visit/time of informed consent/assent diagnosed with mild-moderate AD (according to the criteria of Hanifin and Rajka), of at least 5% BSA.
Has any clinically significant medical disorder, condition, or disease (including active or potentially recurrent non AD dermatological conditions and known genetic dermatological conditions that overlap with AD, such as Netherton syndrome.
Subjects in Cohort 1 are excluded if they have a contraindication for treatment with hydrocortisone butyrate cream 0.1%
Subjects in Cohort 2 are excluded if they have a contraindication for treatment with pimecrolimus cream, 1%
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pimecrolimus cream, 1% Pimecrolimus cream, 1% This treatment arm will be administered in Cohort 2 only. Crisaborole ointment, 2% Crisaborole ointment, 2% This treatment arm will be administered both in Cohort 1 and Cohort 2. Hydrocortisone butyrate cream, 0.1% Hydrocortisone butyrate cream, 0.1% This treatment arm will be administered in Cohort 1 only. Crisaborole Vehicle Crisaborole Vehicle This treatment arm will be administered both in Cohort 1 and Cohort 2.
- Primary Outcome Measures
Name Time Method Percent Change From Baseline in the Eczema Area and Severity Index (EASI) Total Score at Day 29 Baseline, Day 29 EASI quantifies severity of participant's AD (excluded scalp) based on lesion severity and percent (%) body surface area (%BSA) affected. Lesion severity included erythema (E), induration/papulation (I), excoriation (Ex), lichenification (L) scored for 4 regions (head and neck \[h\], upper limbs \[u\], trunk \[t\] \[including axillae, groin\], lower limbs \[l\] \[including buttocks\]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score (A) based upon %BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 to \<70%), 5 (70 to \<90%), 6 (90 to 100%). Total EASI score (aged \>=8 years) =0.1\*Ah\*(Eh + Ih + Exh + Lh) + 0.2\*Au\*(Eu + Iu + Exu + Lu) + 0.3\*At\*(Et + It +Ext + Lt) + 0.4\*Al\*(El + Il + Exl + Ll); for aged 2 to \<8 years =0.2\*Ah\*(Eh + Ih + Exh + Lh) + 0.2\*Au\*(Eu + Iu + Exu + Lu) + 0.3\*At\*(Et +It + Ext + Lt) + 0.3\*Al\*(El + Il + Exl + Ll). Total score ranges from 0.0 to 72.0, higher scores indicated greater AD severity.
Number of Participants With Clinically Significant Changes in Vital Signs Screening up to Day 29 Vital sign measurements included temperature, respiratory rate, pulse rate, and blood pressure. Temperature, respiratory rate, pulse rate, and blood pressure were taken in the seated or supine position, after the participant has been sitting or lying calmly for a minimum of 5 minutes (when possible for younger children). Position of recording was consistent within participant through-out the study.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment Discontinuations Due to AEs and SAEs From Baseline up to 28 days after last dose of study treatment (maximum up to 60 Days) An AE is any untoward medical occurrence in a study participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. TEAEs are events between the first dose of study drug up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A SAE is any untoward medical occurrence at any dose that: results in death; is life-threatening (immediate risk of death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); results in congenital anomaly/birth defect; or that is considered to be an important medical event.
Number of Participants With Local Tolerability Adverse Events (AEs) From Baseline up to 28 days after last dose of study treatment (maximum up to 60 Days) Local tolerability AEs included application and instillation site reactions, application site discharge, application site erythema, application site exfoliation, application site pain, application site pruritus, application site swelling, dermatitis and eczema, dermatitis atopic, dermatitis contact, eczema, skin irritation, telangiectasia and related conditions, and urticarias.
Number of Participants With Clinically Significant Abnormal Laboratory Parameters Screening up to Day 29 Hematology parameters included with criteria greater than (\>) 1.2\*upper limit of normal (ULN): leukocytes (10\^3 per cubic millimeter \[10\^3/mm\^3\]), lymphocytes (10\^3/mm\^3), lymphocytes/leukocytes (%), neutrophils (10\^3/mm\^3), neutrophils/leukocytes (%), basophils/leukocytes (%), eosinophils (10\^3/mm\^3), eosinophils/leukocytes (%), monocytes (10\^3/mm\^3), monocytes/leukocytes (%). Clinical chemistry included parameters: aspartate aminotransferase (units per liter \[U/L\]) (\>3.0\* ULN), alanine aminotransferase (U/L) (\>3.0\* ULN), alkaline phosphatase (U/L) (\>3.0\* ULN), creatinine (milligram per deciliter \[mg/dL\]) (\>1.3\* ULN), potassium (milliequivalent per liter \[mEq/L\]) (\>1.1\* ULN), bicarbonate (mEq/L) (\>1.1\* ULN).
- Secondary Outcome Measures
Name Time Method Number of Participants Who Achieved Investigator's Static Global Assessment (ISGA) Score of Clear (0) or Almost Clear (1) at Day 8, 15, 22 and 29 Day 8, 15, 22 and 29 ISGA is a five point global assessment scale of AD severity, used to characterize participants' overall disease severity across all treatable AD lesions (excluding the scalp). ISGA score ranged from 0 to 4: where 0 = clear (minor residual hypo/hyperpigmentation; no erythema or induration/papulation; no oozing/crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration/papulation and no oozing/crusting), 2= mild (faint pink erythema with mild induration/papulation and no oozing/crusting), 3= moderate (pink-red erythema with moderate induration/papulation with or without oozing/crusting), 4= severe (deep or bright red erythema with severe induration/papulation and with oozing/crusting). Higher scores indicated greater severity of AD.
Change From Baseline in Percent Body Surface Area (%BSA) at Day 8, 15, 22 and 29 Baseline, Day 8, 15, 22 and 29 Four body regions were evaluated: head and neck, upper limbs, trunk (including axillae) and lower limbs (including buttocks) excluding scalp. BSA was calculated using handprint method. Number of handprints (size of participant's full palmer hand in a closed position) fitting in affected area of a body region was estimated. Maximum number of handprints were: 10 for head, neck (20 for \<8 years age), 20 for upper limbs, 30 for trunk, 40 for lower limbs (30 for \<8 years age). Surface area (SA) of body region equivalent to 1 handprint: 10% for head, neck (5% for \<8 years age), 5% for upper limbs, 3.33% for trunk, 2.5% for lower limbs (3.33% for \<8 years age). Overall %BSA for a body region = total number of handprints in a body region \* % SA equivalent to 1 handprint. % BSA for an individual: mean of % BSA of all 4 body regions, range =0-100%, higher values = greater AD severity.
Number of Participants Who Achieved >=3 Point Improvement From Baseline in Peak Pruritus Numeric Rating Scale (NRS) in Participants Aged Greater Than or Equal to (>=) 12 Years at Day 8, 15, 22 and 29 Day 8, 15, 22 and 29 The severity of itch (pruritus) due to AD was assessed using the Peak Pruritus NRS for participants aged \>=12 years. Participants at specified time points were asked the following question: "how would you rate your itch at the worst moment during the previous 24 hours?" The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Time to First Improvement From Baseline in Eczema Area and Severity Index (EASI) Total Score of Greater Than or Equal to (>=) 75% Baseline up to Day 43 EASI quantifies severity of participant's AD (excluded scalp) based on lesion severity and %BSA affected. Lesion severity included erythema (E), induration/papulation (I), excoriation (Ex), lichenification (L) scored for 4 regions (head and neck \[h\], upper limbs \[u\], trunk \[t\] \[including axillae, groin\], lower limbs \[l\] \[including buttocks\]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score(A) based upon %BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 to \<70%), 5 (70 to \<90%), 6 (90 to 100%). Total EASI score (aged \>=8 years) =0.1\*Ah\*(Eh + Ih + Exh + Lh) + 0.2\*Au\*(Eu + Iu + Exu + Lu) + 0.3\*At\*(Et + It +Ext + Lt) + 0.4\*Al\*(El + Il + Exl + Ll); for aged 2 to \<8 years =0.2\*Ah\*(Eh + Ih + Exh + Lh) + 0.2\*Au\*(Eu + Iu + Exu + Lu) + 0.3\*At\*(Et +It + Ext + Lt) + 0.3\*Al\*(El + Il + Exl + Ll). Total score ranges from 0.0 to 72.0, higher scores indicated greater AD severity.
Number of Participants Who Achieved >=2 Point Improvement From Baseline in Peak Pruritus Numeric Rating Scale (NRS) in Participants Aged Greater Than or Equal to (>=) 12 Years at Day 8, 15, 22 and 29 Day 8, 15, 22 and 29 The severity of itch (pruritus) due to AD was assessed using the peak pruritus NRS for participants aged \>=12 years. Participants at specified time points were asked the following question: "how would you rate your itch at the worst moment during the previous 24 hours?" The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Number of Participants Who Achieved Success in the Investigator's Static Global Assessment (ISGA) (ISGA Score of Clear [0] or Almost Clear [1] With At-least a 2-Grade Improvement From Baseline) at Day 8, 15, 22 and 29 Day 8, 15, 22 and 29 ISGA is a five point global assessment scale of AD severity, used to characterize participants' overall disease severity across all treatable AD lesions (excluding the scalp). ISGA score ranged from 0 to 4: where 0= clear (minor residual hypo/hyperpigmentation; no erythema or induration/papulation; no oozing/crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration/papulation and no oozing/crusting), 2= mild (faint pink erythema with mild induration/papulation and no oozing/crusting), 3= moderate (pink-red erythema with moderate induration/papulation with or without oozing/crusting), 4= severe (deep or bright red erythema with severe induration/papulation and with oozing/crusting). Higher scores indicated greater severity of AD.
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Day 8, 15 and 22 Baseline, Day 8, 15 and 22 EASI quantifies severity of participant's AD (excluded scalp) based on lesion severity and %BSA affected. Lesion severity included erythema (E), induration/papulation (I), excoriation (Ex), lichenification (L) scored for 4 regions (head and neck \[h\], upper limbs \[u\], trunk \[t\] \[including axillae, groin\], lower limbs \[l\] \[including buttocks\]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score(A) based upon %BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 to \<70%), 5 (70 to \<90%), 6 (90 to 100%). Total EASI score (aged \>=8 years) =0.1\*Ah\*(Eh + Ih + Exh + Lh) + 0.2\*Au\*(Eu + Iu + Exu + Lu) + 0.3\*At\*(Et + It +Ext + Lt) + 0.4\*Al\*(El + Il + Exl + Ll); for aged 2 to \<8 years =0.2\*Ah\*(Eh + Ih + Exh + Lh) + 0.2\*Au\*(Eu + Iu + Exu + Lu) + 0.3\*At\*(Et +It + Ext + Lt) + 0.3\*Al\*(El + Il + Exl + Ll). Total score ranges from 0.0 to 72.0, higher scores indicated greater AD severity.
Number of Participants Who Achieved Greater Than or Equal to (>=) 75 Percent (%) Improvement From Baseline in Eczema Area and Severity Index (EASI) Total Score at Day 8, 15, 22 and 29 Day 8, 15, 22 and 29 EASI quantifies severity of participant's AD (excluded scalp) based on lesion severity and %BSA affected. Lesion severity included erythema (E), induration/papulation (I), excoriation (Ex), lichenification (L) scored for 4 regions (head and neck \[h\], upper limbs \[u\], trunk \[t\] \[including axillae, groin\], lower limbs \[l\] \[including buttocks\]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score(A) based upon %BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 to \<70%), 5 (70 to \<90%), 6 (90 to 100%). Total EASI score (aged \>=8 years) =0.1\*Ah\*(Eh + Ih + Exh + Lh) + 0.2\*Au\*(Eu + Iu + Exu + Lu) + 0.3\*At\*(Et + It +Ext + Lt) + 0.4\*Al\*(El + Il + Exl + Ll); for aged 2 to \<8 years =0.2\*Ah\*(Eh + Ih + Exh + Lh) + 0.2\*Au\*(Eu + Iu + Exu + Lu) + 0.3\*At\*(Et +It + Ext + Lt) + 0.3\*Al\*(El + Il + Exl + Ll). Total score ranges from 0.0 to 72.0, higher scores indicated greater AD severity.
Change From Baseline in Peak Pruritus Numerical Rating Scale (NRS) in Participants Aged Greater Than or Equal to (>=) 12 Years at Day 8, 15, 22 and 29 Baseline, Day 8, 15, 22 and 29 The severity of itch (pruritus) due to AD was assessed using the peak pruritus NRS for participants aged \>=12 years. Participants at specified time points were asked the following question: "how would you rate your itch at the worst moment during the previous 24 hours?" The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Time >=2 Point to Improvement From Baseline in Observer Reported Itch Severity Scale in Participants Aged Less Than (<) 6 Years Baseline up to Day 29 The severity of itch (pruritus) due to AD was assessed using the patient reported itch severity scale for participants aged \<6 years. Participant's caregivers at specified time points were asked the following question "how would you rate your observation of your child's itch (scratching, rubbing) at the worst moment during the previous 24 hours?". The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Time to >=3 Point Improvement From Baseline in Observer Reported Itch Severity Scale in Participants Aged Less Than (<) 6 Years Baseline up to Day 29 The severity of itch (pruritus) due to AD was assessed using the Patient Reported Itch Severity Scale for participants aged \<6 years. Participant's caregivers at specified time points were asked the following question "how would you rate your observation of your child's itch (scratching, rubbing) at the worst moment during the previous 24 hours?". The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Number of Participants Who Achieved Greater Than or Equal to (>=) 2 Point Improvement From Baseline in Observer Reported Itch Severity Scale in Participants Aged Less Than (<) 6 Years at Day 8, 15, 22 and 29 Day 8, 15, 22 and 29 The severity of itch (pruritus) due to AD was assessed using the Patient Reported Itch Severity Scale for participants aged \<6 years. Participant's caregivers at specified time points were asked the following question "how would you rate your observation of your child's itch (scratching, rubbing) at the worst moment during the previous 24 hours?". The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Change From Baseline in Participant Reported Itch Severity Scale in Participants Aged 6-11 Years at Day 8, 15, 22 and 29 Baseline, Day 8, 15, 22 and 29 The severity of itch (pruritus) due to AD was assessed using the five-category participant reported itch severity scale for participants aged 6-11 years. Participants at specified time points were asked to "circle the face that shows how itchy your skin has been today". The scale ranged from 0 to 4, where 0= no itch and 4= very itch. Higher scores indicated worse itch.
Change From Baseline in Observer Reported Itch Severity Scale in Participants Aged Less Than (<) 6 Years at Day 8, 15, 22 and 29 Baseline, Day 8, 15, 22 and 29 The severity of itch (pruritus) due to AD was assessed using the participant reported itch severity scale for participants aged \<6 years. Participant's caregivers at specified time points were asked the following question "how would you rate your observation of your child's itch (scratching, rubbing) at the worst moment during the previous 24 hours?". The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Time to Greater Than or Equal to (>=2) Point Improvement From Baseline in Peak Pruritus Numeric Rating Scale (NRS) in Participants Aged Greater Than (>) 12 Years Baseline up to Day 29 The severity of itch (pruritus) due to AD was assessed using the peak pruritus NRS for participants aged \>12 years. Participants at specified time points were asked the following question: "how would you rate your itch at the worst moment during the previous 24 hours?" The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Time to >= 3 Point Improvement From Baseline in Peak Pruritus Numeric Rating Scale (NRS) in Participants Aged Greater Than (>)12 Years Baseline up to Day 29 The severity of itch (pruritus) due to AD was assessed using the Peak Pruritus NRS for participants aged \>12 years. Participants at specified time points were asked the following question: "how would you rate your itch at the worst moment during the previous 24 hours?" The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Number of Participants Who Achieved Greater Than or Equal to (>=) 3 Point Improvement From Baseline in Observer Reported Itch Severity Scale in Participants Aged Less Than (<) 6 Years at Day 8, 15, 22 and 29 Day 8, 15, 22 and 29 The severity of itch (pruritus) due to AD was assessed using the Patient Reported Itch Severity Scale for participants aged \<6 years. Participant's caregivers at specified time points were asked the following question "how would you rate your observation of your child's itch (scratching, rubbing) at the worst moment during the previous 24 hours?". The scale ranged from 0 to 10, where 0= no itch and 10= worst itch imaginable. Higher scores indicated worse itch.
Change From Baseline in Dermatology Life Quality Index (DLQI) in Participants Greater Than or Equal to (>=) 16 Years at Day 8, 15, 22 and 29 Baseline, Day 8, 15, 22 and 29 DLQI is a 10-item questionnaire that measures the impact of skin disease on participants aged \>=16 years. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicated more impact on quality of life. Scores from all 10 questions were added up to give DLQI total score range from 0 (not at all) to 30 (very much). Higher scores indicated more impact on quality of life of participant.
Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) in Participants Aged 4-15 Years at Day 8, 15, 22 and 29 Baseline, Day 8, 15, 22 and 29 The CDLQI was a 10-item questionnaire that measures the impact of skin disease on children's (aged 4 to 15 years) quality of life. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicate more impact on quality of life. The CDLQI total score was the sum of individual scores of question 1-10 and ranged from 0 (not at all) to 30 (very much): 0-1 = no effect on the child's life; 2-6 = small effect; 7-12 = moderate effect; 13-18 = very large effect; 19-30 = extremely large effect. Higher scores indicated more impact on quality of life of children.
Change From Baseline in Dermatitis Family Impact Questionnaire (DFI) in Participants Aged 2-17 Years at Day 8, 15, 22 and 29 Baseline, Day 8, 15, 22 and 29 The DFI was a 10-item disease questionnaire that measures the impact of having a child (aged 2-17 years) with AD on family quality of life. It was completed by parent/legal guardian of the child (affected by AD), based on recall over the past week. Each question was scored on a 4-point scale ranging from 0 (not at all) to 30 (very much): where higher scores indicated worst quality of life of family. The DFI total score was the sum of individual scores of the 10 questions and ranged from 0 (no impact on life of family) to 30 (maximum effect on life of family), where higher DFI scores indicated maximum effect on life of family.
Trial Locations
- Locations (32)
Arlington Research Center, Inc.
🇺🇸Arlington, Texas, United States
Universitatsklinikum Schleswig-Holstein, Campus Lubeck
🇩🇪Lubeck, Schleswig-holstein, Germany
Barbara Rewerska Diamond Clinic
🇵🇱Krakow, Malopolska, Poland
Dermatology Trial Associates
🇺🇸Bryant, Arkansas, United States
NHS Tayside, Ninewells Hospital and Medical School
🇬🇧Dundee, Scotland, United Kingdom
Silmedic sp. z o.o
🇵🇱Katowice, Poland
Krakowskie Centrum Medyczne sp. z o.o.
🇵🇱Krakow, Poland
Centre Hospitalier Universitaire Vaudois (CHUV)
🇨🇭Lausanne, Switzerland
ISA - Interdisciplinary Study Association GmbH
🇩🇪Berlin, Germany
DiSSal Sezione di Dermatologia Az. Ospedaliera Universitaria
🇮🇹Genova, GE, Italy
Avdelningen for Kliniska Provningar
🇸🇪Orebro, Sweden
Universitatsklinikum Bonn
🇩🇪Bonn, NRW, Germany
Klinikum der Universitat Munchen
🇩🇪Munchen, Bayern, Germany
Fachklinik Bad Bentheim, Fachbereich Dermatologie und Allergologie, Dermatologische Ambulanz
🇩🇪Bad Bentheim, Niedersachsen, Germany
M3-Wake Research, Inc.
🇺🇸Raleigh, North Carolina, United States
California Dermatology & Clinical Research Institute
🇺🇸Encinitas, California, United States
Ospedale San Pietro Fatebenefratelli
🇮🇹Roma, RM, Italy
Rame Medical Ltd, Penntorr Health
🇬🇧Torpoint, Cornwall, United Kingdom
Klinika Ambroziak Sp. z O. O.
🇵🇱Warszawa, Poland
ROYALDERM Agnieszka Nawrocka
🇵🇱Warszawa, Poland
Universitatsklinik fuer Dermatologie
🇨🇭Bern, Switzerland
UOSD Dermatologia Gen. ed Oncologica DU, PO San Salvatore
🇮🇹L'Aquila, AQ, Italy
Azienda Ospedaliero - Universitaria Policlinico Tor Vergata
🇮🇹Roma, Rome, Italy
Universitats-Kinderspital Zurich
🇨🇭Zurich, Switzerland
Barn och Ungdomskliniken
🇸🇪Orebro, Sweden
Park Avenue Dermatology
🇺🇸Orange Park, Florida, United States
Lenus Research & Medical Group, LLC
🇺🇸Sweetwater, Florida, United States
DS Research
🇺🇸Louisville, Kentucky, United States
Tanner Clinic
🇺🇸Layton, Utah, United States
Virginia Clinical Research, Inc
🇺🇸Norfolk, Virginia, United States
Universitaetsklinikum Frankfurt
🇩🇪Frankfurt am Main, Germany
ForCare Clinical Research
🇺🇸Tampa, Florida, United States