NCT03733301: BREEZE-AD7

A Study of Baricitinib (LY3009104) in Combination With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis

Completed Phase 3 Results posted Last updated 11 August 2020

What this trial tests

Phase 3 trial testing Baricitinib in Atopic Dermatitis in 329 participants. Completed in 22 August 2019.

Timeline

16 November 2018

Primary endpoint
29 July 2019

22 August 2019

Quick facts

Lead sponsor	Eli Lilly and Company
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	329
Start date	16 November 2018
Primary completion	29 July 2019
Estimated completion	22 August 2019
Sites	68 locations across Italy, Japan, Austria, Taiwan, Germany, Poland, South Korea, Argentina

Drugs / interventions tested

• Baricitinib (baricitinib) — full drug profile →
• Topical corticosteroid — full drug profile →
• Placebo

Conditions studied

• Atopic Dermatitis — all drugs for Atopic Dermatitis →

Sponsor

Eli Lilly and Company — full company profile →

Who can join

18 and older, any sex, with Atopic Dermatitis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 With a ≥ 2 Point Improvement Primary · 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.

Group	Value	95% CI
Placebo	14.7
2 mg Baricitinib	23.9
4 mg Baricitinib	30.6

Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) Secondary · 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

Group	Value	95% CI
Placebo	22.9
2 mg Baricitinib	43.1
4 mg Baricitinib	47.7

Percentage of Participants Achieving EASI90 Secondary · 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

Group	Value	95% CI
Placebo	13.8
2 mg Baricitinib	16.5
4 mg Baricitinib	24.3

Percent Change From Baseline on EASI Score Secondary · 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

Group	Value	95% CI
Placebo	-45.08	± 3.828
2 mg Baricitinib	-58.16	± 3.689
4 mg Baricitinib	-67.21	± 3.679

Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75) Secondary · 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)

Group	Value	95% CI
Placebo	7.3
2 mg Baricitinib	11.0
4 mg Baricitinib	18.0

Percentage of Participants Achieving a 4-Point Improvement in Itch Numeric Rating Scale (NRS) Secondary · 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.

Group	Value	95% CI
Placebo	20.2
2 mg Baricitinib	38.1
4 mg Baricitinib	44.0

Change From Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS) Secondary · 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

Group	Value	95% CI
Placebo	-0.51	± 0.151
2 mg Baricitinib	-1.33	± 0.147
4 mg Baricitinib	-1.42	± 0.147

Change From Baseline in Skin Pain NRS Secondary · 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.

Group	Value	95% CI
Placebo	-2.06	± 0.231
2 mg Baricitinib	-3.22	± 0.224
4 mg Baricitinib	-3.73	± 0.226

Percentage of Participants Achieving EASI50 Secondary · 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

Group	Value	95% CI
Placebo	41.3
2 mg Baricitinib	64.2
4 mg Baricitinib	70.3

Percentage of Participants Achieving IGA of 0 Secondary · 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.

Group	Value	95% CI
Placebo	2.8
2 mg Baricitinib	3.7
4 mg Baricitinib	8.1

Change From Baseline in SCORAD Secondary · 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 (

Group	Value	95% CI
Placebo	-21.40	± 1.941
2 mg Baricitinib	-29.88	± 1.867
4 mg Baricitinib	-35.78	± 1.862

Percentage of Participants Achieving SCORAD90 Secondary · 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 (

Group	Value	95% CI
Placebo	0.9
2 mg Baricitinib	3.7
4 mg Baricitinib	7.2

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to 20 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 4/108 (4%)

Deaths: 0/108

2 mg Baricitinib

Serious: 2/109 (2%)

Deaths: 0/109

4 mg Baricitinib

Serious: 4/111 (4%)

Deaths: 0/111

Serious adverse events (10 terms)

Reaction	System	Placebo	2 mg Baricitinib	4 mg Baricitinib
Cataract	Eye disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Eye infection toxoplasmal	Infections and infestations	—	—	—
Postoperative abscess	Infections and infestations	—	—	—
Skin laceration	Injury, poisoning and procedural complications	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	—	—	—
Asthma	Respiratory, thoracic and mediastinal disorders	—	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—	—
Dermatitis atopic	Skin and subcutaneous tissue disorders	—	—	—

Other adverse events (3 terms — click to expand)

Reaction	System	Placebo	2 mg Baricitinib	4 mg Baricitinib
Nasopharyngitis	Infections and infestations	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—
Folliculitis	Infections and infestations	—	—	—

Most-reported serious reactions: Cataract, Abdominal pain, Eye infection toxoplasmal, Postoperative abscess, Skin laceration, Back pain, Intervertebral disc protrusion, Asthma.

Data from ClinicalTrials.gov NCT03733301 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. JAK inhibitors in the treatment of atopic dermatitis.
   Chovatiya R, Paller AS. · · 2021 · cited 258× · PMID 34437922 · DOI 10.1016/j.jaci.2021.08.009
2. Efficacy and Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial.
   Reich K, Kabashima K, Peris K, Silverberg JI, et al · · 2020 · cited 202× · PMID 33001140 · DOI 10.1001/jamadermatol.2020.3260
3. JAK-STAT signaling pathway in the pathogenesis of atopic dermatitis: An updated review.
   Huang IH, Chung WH, Wu PC, Chen CB. · · 2022 · cited 195× · PMID 36569854 · DOI 10.3389/fimmu.2022.1068260
4. Targeting the Janus Kinase Family in Autoimmune Skin Diseases.
   Howell MD, Kuo FI, Smith PA. · · 2019 · cited 180× · PMID 31649667 · DOI 10.3389/fimmu.2019.02342
5. The translational revolution in atopic dermatitis: the paradigm shift from pathogenesis to treatment.
   Facheris P, Jeffery J, Del Duca E, Guttman-Yassky E. · · 2023 · cited 150× · PMID 36928371 · DOI 10.1038/s41423-023-00992-4
6. Tyrosine Kinases in Autoimmune and Inflammatory Skin Diseases.
   Szilveszter KP, Németh T, Mócsai A. · · 2019 · cited 102× · PMID 31447854 · DOI 10.3389/fimmu.2019.01862
7. New and Emerging Systemic Treatments for Atopic Dermatitis.
   Newsom M, Bashyam AM, Balogh EA, Feldman SR, et al · · 2020 · cited 76× · PMID 32519223 · DOI 10.1007/s40265-020-01335-7
8. Emerging systemic JAK inhibitors in the treatment of atopic dermatitis: a review of abrocitinib, baricitinib, and upadacitinib.
   Nezamololama N, Fieldhouse K, Metzger K, Gooderham M. · · 2020 · cited 69× · PMID 33240390 · DOI 10.7573/dic.2020-8-5