NCT03334396: BREEZE-AD1

A Study of Baricitinib (LY3009104) in Patients With Moderate to Severe Atopic Dermatitis

Completed Phase 3 Results posted Last updated 18 August 2020

What this trial tests

Phase 3 trial testing Baricitinib in Atopic Dermatitis in 660 participants. Completed in 16 August 2019.

Timeline

23 November 2017

Primary endpoint
6 December 2018

16 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	660
Start date	23 November 2017
Primary completion	6 December 2018
Estimated completion	16 August 2019
Sites	93 locations across Denmark, France, Italy, Japan, Russia, Taiwan, Germany, Mexico

Drugs / interventions tested

• Baricitinib (baricitinib) — 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 (Placebo, 2 mg, or 4 mg Baricitinib) Primary · 16 Weeks

The IGA measures the investigator's 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) 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	4.8
2 mg Baricitinib	11.4
4 mg Baricitinib	16.8

Percentage of Participants Achieving IGA of 0 or 1 With a ≥ 2 Point Improvement (Placebo, 1 mg Baricitinib) Secondary · 16 Weeks

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	4.8
1 mg Baricitinib	11.8

Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) Secondary · 16 Weeks

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	8.8
1 mg Baricitinib	17.3
2 mg Baricitinib	18.7
4 mg Baricitinib	24.8

Percentage of Participants Achieving EASI90 Secondary · 16 Weeks

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	4.8
1 mg Baricitinib	8.7
2 mg Baricitinib	10.6
4 mg Baricitinib	16.0

Percent Change From Baseline in EASI Score Secondary · Baseline, 16 Weeks

The EASI assesses objective physician estimates of 2 dimensions of AD - 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

Group	Value	95% CI
Placebo	-34.82	± 3.64
1 mg Baricitinib	-48.22	± 4.52
2 mg Baricitinib	-51.89	± 4.29
4 mg Baricitinib	-59.36	± 3.84

Percentage of Participants Achieving SCORing Atopic Dermatitis 75 (SCORAD75) Secondary · 16 Weeks

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 visual analog scale (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	1.2
1 mg Baricitinib	5.5
2 mg Baricitinib	7.3
4 mg Baricitinib	10.4

Percentage of Participants Achieving a 4-Point Improvement in Itch Numeric Rating Scale (NRS) Secondary · 16 Weeks

The Itch Numeric Rating Scale (NRS) is a participant-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 participants 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	7.2
1 mg Baricitinib	10.5
2 mg Baricitinib	12.0
4 mg Baricitinib	21.5

Change From Baseline in the Score of Item 2 of the Atopic Dermatitis Sleep Scale (ADSS) Secondary · Baseline, 16 Weeks

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 c

Group	Value	95% CI
Placebo	-0.84	± 0.15
1 mg Baricitinib	-1.21	± 0.18
2 mg Baricitinib	-1.04	± 0.17
4 mg Baricitinib	-1.42	± 0.16

Change From Baseline in the Skin Pain Numeric Rating Scale (NRS) Secondary · Baseline, 16 Weeks

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, 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	-0.84	± 0.24
1 mg Baricitinib	-1.92	± 0.30
2 mg Baricitinib	-1.58	± 0.29
4 mg Baricitinib	-1.93	± 0.26

Percentage of Participants Achieving EASI50 Secondary · 16 Weeks

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

Group	Value	95% CI
Placebo	15.3
1 mg Baricitinib	26.0
2 mg Baricitinib	30.1
4 mg Baricitinib	41.6

Percentage of Participants Achieving IGA of 0 Secondary · 16 Weeks

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	0.8
1 mg Baricitinib	1.6
2 mg Baricitinib	2.4
4 mg Baricitinib	1.6

Change From Baseline in SCORAD Secondary · Baseline, 16 Weeks

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	-13.51	± 2.00
1 mg Baricitinib	-18.85	± 2.48
2 mg Baricitinib	-21.47	± 2.36
4 mg Baricitinib	-28.30	± 2.10

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: 6/249 (2%)

Deaths: 0/249

1 mg Baricitinib

Serious: 1/127 (1%)

Deaths: 0/127

2 mg Baricitinib

Serious: 0/123 (0%)

Deaths: 0/123

4 mg Baricitinib

Serious: 2/125 (2%)

Deaths: 0/125

Placebo Maximum Extended Enrollment

Serious: 0/15 (0%)

Deaths: 0/15

1 mg Baricitinib Maximum Extended Enrollment

Serious: 0/5 (0%)

Deaths: 0/5

2 mg Baricitinib Maximum Extended Enrollment

Serious: 0/8 (0%)

Deaths: 0/8

4 mg Baricitinib Maximum Extended Enrollment

Serious: 0/8 (0%)

Deaths: 0/8

Serious adverse events (7 terms)

Reaction	System	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib	Placebo Maximum Extended E…	1 mg Baricitinib Maximum E…	2 mg Baricitinib Maximum E…	4 mg Baricitinib Maximum E…
Dermatitis atopic	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—
Alcohol poisoning	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—
Clavicle fracture	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—
Rib fracture	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—	—
Papillary thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—	—
Suicide attempt	Psychiatric disorders	—	—	—	—	—	—	—	—

Other adverse events (19 terms — click to expand)

Reaction	System	Placebo	1 mg Baricitinib	2 mg Baricitinib	4 mg Baricitinib	Placebo Maximum Extended E…	1 mg Baricitinib Maximum E…	2 mg Baricitinib Maximum E…	4 mg Baricitinib Maximum E…
Nasopharyngitis	Infections and infestations	—	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—	—	—
Oral herpes	Infections and infestations	—	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—
Leukopenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—
Lymphopenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—
Oedema	General disorders	—	—	—	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—	—	—	—
Skin infection	Infections and infestations	—	—	—	—	—	—	—	—
Vulvovaginal candidiasis	Infections and infestations	—	—	—	—	—	—	—	—
Weight decreased	Investigations	—	—	—	—	—	—	—	—

Most-reported serious reactions: Dermatitis atopic, Alcohol poisoning, Clavicle fracture, Rib fracture, Breast cancer, Papillary thyroid cancer, Suicide attempt.

Data from ClinicalTrials.gov NCT03334396 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the efficacy and safety of baricitinib as monotherapy 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. Emerging Topical and Systemic JAK Inhibitors in Dermatology.
   Solimani F, Meier K, Ghoreschi K. · · 2019 · cited 199× · PMID 31849996 · DOI 10.3389/fimmu.2019.02847
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. Understanding the immune landscape in atopic dermatitis: The era of biologics and emerging therapeutic approaches.
   Moyle M, Cevikbas F, Harden JL, Guttman-Yassky E. · · 2019 · cited 100× · PMID 30825336 · DOI 10.1111/exd.13911
8. A biofabricated vascularized skin model of atopic dermatitis for preclinical studies.
   Liu X, Michael S, Bharti K, Ferrer M, et al · · 2020 · cited 73× · PMID 32059197 · DOI 10.1088/1758-5090/ab76a1