A Study of Baricitinib (LY3009104) in Adult Participants With Moderate to Severe Atopic Dermatitis (BREEZE-AD5)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03435081 |
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Recruitment Status :
Completed
First Posted : February 15, 2018
Results First Posted : January 25, 2021
Last Update Posted : September 9, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Atopic Dermatitis | Drug: Baricitinib Drug: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 440 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib in Adult Patients With Moderate to Severe Atopic Dermatitis |
| Actual Study Start Date : | February 20, 2018 |
| Actual Primary Completion Date : | December 9, 2019 |
| Actual Study Completion Date : | August 16, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: 2 milligram (mg) Baricitinib
2 mg Baricitinib administered orally every day. Placebo administered orally to maintain the blind.
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Drug: Baricitinib
Administered orally
Other Name: LY3009104 Drug: Placebo Administered orally |
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Experimental: 1 mg Baricitinib
1 mg Baricitinib administered orally every day. Placebo administered orally to maintain the blind.
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Drug: Baricitinib
Administered orally
Other Name: LY3009104 Drug: Placebo Administered orally |
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Placebo Comparator: Placebo
Placebo administered orally every day.
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Drug: Placebo
Administered orally |
- Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) (2 mg Baricitinib) [ Time Frame: 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 Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement [ Time Frame: 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.
- Percentage of Participants Achieving EASI75 (1 mg Baricitinib) [ Time Frame: 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 EASI90 [ Time Frame: 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 in EASI Score [ Time Frame: 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 (LS) Means were calculated using a MMRM model with treatment, 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) [ Time Frame: 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 a 4-Point Improvement on the Itch Numeric Rating Scale (NRS) [ Time Frame: 16 Weeks ]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.
- Change From Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS) [ Time Frame: Baseline, Week 16 ]
Atopic Dermatitis Sleep Scale (ADSS) is a 3-item, participant-administered questionnaire developed to assess the impact of itch on sleep including difficulty falling asleep, frequency of waking, and difficulty getting back to sleep last night. 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 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.
- Change From Baseline in Skin Pain NRS [ Time Frame: Baseline, Week 16 ]
Skin Pain NRS is a participant-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, 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 of Participants Achieving EASI50 [ Time Frame: 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 (erythema, edema/papulation, excoriation, and lichenification) each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head and 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 EASI score.
- Percentage of Participants Achieving IGA of 0 [ Time Frame: 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 [ Time Frame: 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, baseline disease severity (IGA), visit and treatment-by-visit interaction as fixed categorial effects and baseline and baseline-by-visit interaction as fixed continuous effects.
- Percentage of Participants Achieving SCORAD90 [ Time Frame: 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. SCORAD90 is defined as a ≥ 90% improvement from baseline in the SCORAD score.
- Change From Baseline in Body Surface Area (BSA) Affected [ Time Frame: Baseline, Week 16 ]
Body surface area 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 a MMRM model with treatment, baseline disease severity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interactions as fixed continuous effects.
- Percentage of Participants Developing Skin Infections Requiring Antibiotic Treatment [ Time Frame: Week 16 ]Percentage of participants developing skin infections requiring antibiotic treatment.
- Percent Change From Baseline in Itch NRS [ Time Frame: 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 a MMRM model with treatment, baseline disease severity (IGA),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 Total Score of the Patient Oriented Eczema Measure (POEM) [ Time Frame: 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 a MMRM model with treatment, 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 [ Time Frame: 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 a MMRM model with treatment, 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 Hospital Anxiety Depression Scale (HADS) [ Time Frame: 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 a MMRM model with treatment, 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 Dermatology Life Quality Index (DLQI) [ Time Frame: 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 little," "a lot," and "very much," with corresponding scores of 0, 1, 2, and 3, respectively, and unanswered or "not relevant" responses scored as "0." Scores range from 0 to 30 ("no impact on participant's life" to "extremely large effect on participant's life"), and a 4-point change from baseline is considered as the minimal clinically important difference threshold.
LS Means were calculated using a MMRM model with treatment, baseline disease severity (IGA),visit, and treatment-by-visit-interaction as fixed categorical 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 [ Time Frame: 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 Mean were calculated using a MMRM model with treatment, 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 European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Index Score United States (US) and United Kingdom (UK) Algorithm [ Time Frame: 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 UK algorithm, with scores ranging from -0.594 to 1, and the US algorithm, with scores ranging from -0.109 to 1, with higher score indicating better health state.
LS Means were calculated using a MMRM model with treatment, baseline disease activity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interactions as fixed continuous effects.
- Change From Baseline on the European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Visual Analog Score (VAS) [ Time Frame: Baseline, Week 16 ]
EQ-5D-5L is a 2-part measurement. The second part is assessed using a visual analog scale (VAS) that ranges 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 a MMRM model with treatment, baseline disease activity (IGA), visit, and treatment-by-visit-interaction as fixed categorical effects and baseline and baseline-by-visit-interactions as fixed continuous effects.
- Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement [ Time Frame: 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Have a diagnosis of atopic dermatitis (AD) at least 12 months before screening.
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Have moderate to severe AD, including all of the following:
- EASI score ≥16
- IGA score of ≥3
- ≥10% of BSA involvement
- Have had inadequate response or intolerance 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.
Exclusion Criteria:
- 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.
- A history of eczema herpeticum within 12 months, and/or a history of 2 or more episode of eczema herpeticum in the past.
- Participants who are currently experiencing a skin infection that requires treatment, or is currently being treated, with topical or systemic antibiotics.
- 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 before randomization
- received prior treatment with any oral Janus kinase (JAK) inhibitor less than 4 weeks before randomization
- received any parenteral corticosteroid administered by intramuscular or intravenous injection within 6 weeks of planned randomization or are anticipated to require parenteral injection of corticosteroids during the study
- have had an intra-articular corticosteroid injection within 6 weeks of planned randomization
- probenecid at the time of randomization that cannot be discontinued for the duration of the study
- Have high blood pressure characterized by a repeated systolic blood pressure >160 millimeters of mercury (mm Hg) or diastolic blood pressure >100 mm Hg.
- Have had major surgery within the past eight weeks or are planning major surgery during the study.
- Have experienced any of the following within 12 weeks of screening: myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage III/IV heart failure.
- Have a history of venous thromboembolic event (VTE), or are considered at high risk for VTE.
- 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.
- Have a current or recent clinically serious viral, bacterial, fungal, or parasitic infection including herpes zoster, tuberculosis.
- Have specific laboratory abnormalities.
- Have received certain treatments that are contraindicated.
- Pregnant or breastfeeding.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03435081
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| Study Director: | Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) | Eli Lilly and Company |
Documents provided by Eli Lilly and Company:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Eli Lilly and Company |
| ClinicalTrials.gov Identifier: | NCT03435081 |
| Other Study ID Numbers: |
17049 I4V-MC-JAIW ( Other Identifier: Eli Lilly and Company ) |
| First Posted: | February 15, 2018 Key Record Dates |
| Results First Posted: | January 25, 2021 |
| Last Update Posted: | September 9, 2022 |
| Last Verified: | August 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Clinical Study Report (CSR) |
| Time Frame: | Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting. |
| Access Criteria: | A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement. |
| URL: | https://vivli.org/ |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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eczema atopic eczema |
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Dermatitis, Atopic Dermatitis Eczema Skin Diseases Skin Diseases, Genetic |
Genetic Diseases, Inborn Skin Diseases, Eczematous Hypersensitivity, Immediate Hypersensitivity Immune System Diseases |