Trial Outcomes & Findings for A Study of Baricitinib (LY3009104) in Participants With Moderate-to-Severe Atopic Dermatitis (NCT NCT02576938)

Last Updated: 2020-06-17

Results Overview

The EASI 50, defined as ≥ 50% reduction from baseline in EASI score, assesses extent of disease based on dividing the skin into 4 regions (head/neck, trunk, upper limbs, and lower limbs) and measures the following clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3.The EASI confers a maximum score of 72 with 0 = clear; 0.1 -1 = almost clear; 1.1 -7 = mild; 7.1 - 21 = moderate; 21.1 - 50 = severe; 50.1 - 72 = very severe.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

124 participants

Primary outcome timeframe

Week 16

Results posted on

2020-06-17

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Placebo administered orally (PO) once daily (QD), for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.	2 mg Baricitinib 2 milligram (mg) Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.	4 mg Baricitinib 4 mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.
Overall Study STARTED	49	37	38
Overall Study Received at Least One Dose of Study Drug	49	37	38
Overall Study COMPLETED	29	25	26
Overall Study NOT COMPLETED	20	12	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo administered orally (PO) once daily (QD), for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.	2 mg Baricitinib 2 milligram (mg) Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.	4 mg Baricitinib 4 mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.
Overall Study Adverse Event	5	3	6
Overall Study Protocol Violation	1	1	1
Overall Study Withdrawal by Subject	3	2	4
Overall Study Lack of Efficacy	9	4	0
Overall Study Lost to Follow-up	2	0	1
Overall Study Physician Decision	0	1	0
Overall Study Met Exclusion Criteria	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=49 Participants Placebo administered orally (PO) once daily (QD), for 16 weeks Triamcinolone 0.1% applied topically also permitted throughout study.	2 mg Baricitinib n=37 Participants 2mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.	4mg Baricitinib n=38 Participants 4mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.	Total n=124 Participants Total of all reporting groups
Age, Continuous	37.3 years STANDARD_DEVIATION 13.49 • n=5 Participants	40.0 years STANDARD_DEVIATION 14.38 • n=7 Participants	36.4 years STANDARD_DEVIATION 14.47 • n=5 Participants	37.8 years STANDARD_DEVIATION 14.03 • n=4 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	15 Participants n=7 Participants	16 Participants n=5 Participants	56 Participants n=4 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	22 Participants n=7 Participants	22 Participants n=5 Participants	68 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	14 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	45 Participants n=5 Participants	33 Participants n=7 Participants	32 Participants n=5 Participants	110 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	16 Participants n=5 Participants	8 Participants n=7 Participants	9 Participants n=5 Participants	33 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	9 Participants n=7 Participants	9 Participants n=5 Participants	25 Participants n=4 Participants
Race (NIH/OMB) White	23 Participants n=5 Participants	20 Participants n=7 Participants	18 Participants n=5 Participants	61 Participants n=4 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	42 Participants n=5 Participants	31 Participants n=7 Participants	32 Participants n=5 Participants	105 Participants n=4 Participants
Region of Enrollment Japan	8 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	20 Participants n=4 Participants
Median EASI Total Score	22.1 units on a scale n=5 Participants	22.1 units on a scale n=7 Participants	19.5 units on a scale n=5 Participants	21.2 units on a scale n=4 Participants

PRIMARY outcome

Timeframe: Week 16

Population: All participants who received at least one dose of study drug and had EASI 50 data at Week 16.

Outcome measures

Outcome measures
Measure	Placebo n=49 Participants Placebo administered orally (PO) once daily (QD), for 16 weeks Triamcinolone 0.1% applied topically also permitted throughout study.	2 mg Baricitinib n=37 Participants 2mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.	4mg Baricitinib n=38 Participants 4mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.
Percentage of Participants With a 50% or Greater Reduction in the Eczema Area and Severity Index (EASI 50)	37 percentage of participants	57 percentage of participants	61 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: All participants who received at least one dose of study drug.

The Eczema Area and Severity Index (EASI) assesses extent of disease based on dividing the skin into 4 regions (head/neck, trunk, upper limbs, and lower limbs) and measures the following clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3.The EASI confers a maximum score of 72 with 0 = clear; 0.1 -1 = almost clear; 1.1 -7 = mild; 7.1 - 21 = moderate; 21.1 - 50 = severe; 50.1 - 72 = very severe. Change from baseline were analyzed with a Mixed-effect Model Repeated Measure (MMRM) with fixed effects for treatment, visit, country, and the treatment-by-visit interaction, plus baseline and baseline-by-visit included as covariates.

Outcome measures

Outcome measures
Measure	Placebo n=49 Participants Placebo administered orally (PO) once daily (QD), for 16 weeks Triamcinolone 0.1% applied topically also permitted throughout study.	2 mg Baricitinib n=37 Participants 2mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.	4mg Baricitinib n=38 Participants 4mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.
Change From Baseline in the EASI at Week 16	-10.84 units on a scale Standard Error 1.62	-16.44 units on a scale Standard Error 1.72	-16.04 units on a scale Standard Error 1.72

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: All participants who received at least one dose of study drug.

The Eczema Area and Severity Index (EASI) assesses extent of disease based on dividing the skin into 4 regions (head/neck, trunk, upper limbs, and lower limbs) and measures the following clinical signs: (1) erythema, (2) edema/papulation, (3) excoriation, and (4) lichenification each on a scale of 0 to 3.The EASI confers a maximum score of 72 with 0 = clear; 0.1 -1 = almost clear; 1.1 -7 = mild; 7.1 - 21 = moderate; 21.1 - 50 = severe; 50.1 - 72 = very severe. Changes from baseline were analyzed with an MMRM with fixed effects for treatment, visit, country, and the treatment-by-visit interaction, plus baseline and baseline-by-visit included as covariates.

Outcome measures

Outcome measures
Measure	Placebo n=49 Participants Placebo administered orally (PO) once daily (QD), for 16 weeks Triamcinolone 0.1% applied topically also permitted throughout study.	2 mg Baricitinib n=37 Participants 2mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.	4mg Baricitinib n=38 Participants 4mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.
Percentage Change From Baseline in the EASI at Week 16	-45.87 units on a scale Standard Error 5.85	-64.19 units on a scale Standard Error 6.20	-64.69 units on a scale Standard Error 6.21

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: All participants who received at least one dose of study drug.

The SCORAD index uses the rule of nines to assess disease extent and evaluates five clinical characteristics to determine disease severity: (1) erythema, (2) edema/papulation, (3) oozing/crusts, (4) excoriation and (5) lichenification. SCORAD also assesses subjective symptoms of pruritus and sleep loss with Visual Analogue Scales (VAS) where 0 is no itch (or sleeplessness) and 10 is the worst imaginable itch (or sleeplessness). These three aspects: extent of disease (A: 0-102), disease severity (B: 0-18) and 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. Changes from baseline were analyzed with an MMRM with fixed effects for treatment, visit, country, and the treatment-by-visit interaction, plus baseline and baseline-by-visit included as covariates.

Outcome measures

Outcome measures
Measure	Placebo n=49 Participants Placebo administered orally (PO) once daily (QD), for 16 weeks Triamcinolone 0.1% applied topically also permitted throughout study.	2 mg Baricitinib n=37 Participants 2mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.	4mg Baricitinib n=38 Participants 4mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.
Change From Baseline in the Scoring Atopic Dermatitis (SCORAD) at Week 16	-11.89 units on a scale Standard Error 2.88	-23.87 units on a scale Standard Error 3.03	-26.54 units on a scale Standard Error 2.97

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: All participants who received at least one dose of study drug and had IGA data at Week 16 .

The IGA consists of a 6-point severity scale to measure characteristics of erythema, infiltration, papulation, oozing and crusting as guidelines for the overall severity assessment. The scale ranges from clear to very severe disease (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe disease and 5 = very severe disease).

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Placebo administered orally (PO) once daily (QD), for 16 weeks Triamcinolone 0.1% applied topically also permitted throughout study.	2 mg Baricitinib n=27 Participants 2mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.	4mg Baricitinib n=29 Participants 4mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.
Change From Baseline in the Investigator's Global Assessment (IGA) at Week 16	-0.9 units on a scale Standard Deviation 0.69	-1.4 units on a scale Standard Deviation 1.31	-1.3 units on a scale Standard Deviation 1.01

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: All participants who have received at least one dose of study drug.

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. Response categories include "Not at all," "A little," "A lot," and "Very much," with corresponding scores of 0, 1, 2, and 3 respectively. Questions 3-10 also have an additional response category of "Not relevant" which is scored as "0". For all questions, if unanswered the question is scored as "0". Totals range from 0 to 30 (less to more impairment). Changes from baseline in DLQI score were analyzed with an MMRM with fixed effects for treatment, time, country, and the treatment-by-visit interaction, plus baseline and baseline-by-visit were included as covariates.

Outcome measures

Outcome measures
Measure	Placebo n=49 Participants Placebo administered orally (PO) once daily (QD), for 16 weeks Triamcinolone 0.1% applied topically also permitted throughout study.	2 mg Baricitinib n=37 Participants 2mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.	4mg Baricitinib n=38 Participants 4mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.
Change From Baseline in the Dermatologic Life Quality Index (DLQI) at Week 16	-6.27 units on a scale Standard Error 0.82	-6.89 units on a scale Standard Error 0.89	-7.96 units on a scale Standard Error 0.86

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: All participants who received at least one dose of study drug.

The Itch 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 participant's itching is indicated by circling the number that best describes the worst level of itching in the past 24 hours. Changes from baseline were analyzed with an MMRM with fixed effects for treatment, time, country, and the treatment-by-visit interaction, plus baseline and baseline-by-visit were included as covariates.

Outcome measures

Outcome measures
Measure	Placebo n=49 Participants Placebo administered orally (PO) once daily (QD), for 16 weeks Triamcinolone 0.1% applied topically also permitted throughout study.	2 mg Baricitinib n=37 Participants 2mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.	4mg Baricitinib n=38 Participants 4mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.
Change From Baseline in the Itch Numerical Rating Scale (NRS) at Week 16	-1.72 units on a scale Standard Error 0.44	-2.61 units on a scale Standard Error 0.47	-2.22 units on a scale Standard Error 0.46

SECONDARY outcome

Timeframe: Week (Wk) 0: Predose, 15-30 minutes (min) postdose; Wk 4: 1.5 - 4 hour (hr) postdose; Wk 8: 4 - 8 hr postdose; Wk 12: Predose; Wk 16: 30 - 90 min postdose.

Population: All participants who received at least 1 dose of study drug and provided at least 1 post-dose PK sample. PK sample was not collected for the placebo group.

Pharmacokinetics (PK): Maximum serum concentration (Cmax) of Baricitinib

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants Placebo administered orally (PO) once daily (QD), for 16 weeks Triamcinolone 0.1% applied topically also permitted throughout study.	2 mg Baricitinib n=38 Participants 2mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.	4mg Baricitinib 4mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.
Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Baricitinib	18.5 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 70.0	37.7 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 38.9	—

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

2 mg Baricitinib

Serious events: 2 serious events

Other events: 13 other events

Deaths: 0 deaths

4mg Baricitinib

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=49 participants at risk Placebo administered orally (PO) once daily (QD), for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.	2 mg Baricitinib n=37 participants at risk 2mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.	4mg Baricitinib n=38 participants at risk 4mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.
Gastrointestinal disorders Large intestine polyp	0.00% 0/49 • Baseline to end of study (up to 5 months)	0.00% 0/37 • Baseline to end of study (up to 5 months)	2.6% 1/38 • Number of events 1 • Baseline to end of study (up to 5 months)
Infections and infestations Bronchitis	0.00% 0/49 • Baseline to end of study (up to 5 months)	2.7% 1/37 • Number of events 1 • Baseline to end of study (up to 5 months)	0.00% 0/38 • Baseline to end of study (up to 5 months)
Infections and infestations Cellulitis	0.00% 0/49 • Baseline to end of study (up to 5 months)	2.7% 1/37 • Number of events 1 • Baseline to end of study (up to 5 months)	0.00% 0/38 • Baseline to end of study (up to 5 months)
Infections and infestations Staphylococcal infection	0.00% 0/49 • Baseline to end of study (up to 5 months)	2.7% 1/37 • Number of events 1 • Baseline to end of study (up to 5 months)	0.00% 0/38 • Baseline to end of study (up to 5 months)
Skin and subcutaneous tissue disorders Eczema	0.00% 0/49 • Baseline to end of study (up to 5 months)	2.7% 1/37 • Number of events 1 • Baseline to end of study (up to 5 months)	0.00% 0/38 • Baseline to end of study (up to 5 months)

Other adverse events

Other adverse events
Measure	Placebo n=49 participants at risk Placebo administered orally (PO) once daily (QD), for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.	2 mg Baricitinib n=37 participants at risk 2mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.	4mg Baricitinib n=38 participants at risk 4mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study.
Blood and lymphatic system disorders Lymphopenia	6.1% 3/49 • Number of events 3 • Baseline to end of study (up to 5 months)	0.00% 0/37 • Baseline to end of study (up to 5 months)	2.6% 1/38 • Number of events 1 • Baseline to end of study (up to 5 months)
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/49 • Baseline to end of study (up to 5 months)	5.4% 2/37 • Number of events 2 • Baseline to end of study (up to 5 months)	0.00% 0/38 • Baseline to end of study (up to 5 months)
Gastrointestinal disorders Nausea	0.00% 0/49 • Baseline to end of study (up to 5 months)	5.4% 2/37 • Number of events 2 • Baseline to end of study (up to 5 months)	0.00% 0/38 • Baseline to end of study (up to 5 months)
Infections and infestations Cellulitis	6.1% 3/49 • Number of events 4 • Baseline to end of study (up to 5 months)	2.7% 1/37 • Number of events 3 • Baseline to end of study (up to 5 months)	0.00% 0/38 • Baseline to end of study (up to 5 months)
Infections and infestations Nasopharyngitis	4.1% 2/49 • Number of events 2 • Baseline to end of study (up to 5 months)	2.7% 1/37 • Number of events 1 • Baseline to end of study (up to 5 months)	10.5% 4/38 • Number of events 4 • Baseline to end of study (up to 5 months)
Infections and infestations Staphylococcal infection	0.00% 0/49 • Baseline to end of study (up to 5 months)	5.4% 2/37 • Number of events 3 • Baseline to end of study (up to 5 months)	0.00% 0/38 • Baseline to end of study (up to 5 months)
Infections and infestations Subcutaneous abscess	2.0% 1/49 • Number of events 1 • Baseline to end of study (up to 5 months)	0.00% 0/37 • Baseline to end of study (up to 5 months)	5.3% 2/38 • Number of events 2 • Baseline to end of study (up to 5 months)
Infections and infestations Upper respiratory tract infection	2.0% 1/49 • Number of events 1 • Baseline to end of study (up to 5 months)	2.7% 1/37 • Number of events 1 • Baseline to end of study (up to 5 months)	5.3% 2/38 • Number of events 2 • Baseline to end of study (up to 5 months)
Injury, poisoning and procedural complications Procedural pain	2.0% 1/49 • Number of events 2 • Baseline to end of study (up to 5 months)	0.00% 0/37 • Baseline to end of study (up to 5 months)	5.3% 2/38 • Number of events 3 • Baseline to end of study (up to 5 months)
Investigations Blood creatine phosphokinase increased	2.0% 1/49 • Number of events 1 • Baseline to end of study (up to 5 months)	2.7% 1/37 • Number of events 1 • Baseline to end of study (up to 5 months)	13.2% 5/38 • Number of events 5 • Baseline to end of study (up to 5 months)
Investigations White blood cell count decreased	0.00% 0/49 • Baseline to end of study (up to 5 months)	0.00% 0/37 • Baseline to end of study (up to 5 months)	5.3% 2/38 • Number of events 3 • Baseline to end of study (up to 5 months)
Nervous system disorders Headache	0.00% 0/49 • Baseline to end of study (up to 5 months)	5.4% 2/37 • Number of events 3 • Baseline to end of study (up to 5 months)	13.2% 5/38 • Number of events 5 • Baseline to end of study (up to 5 months)
Skin and subcutaneous tissue disorders Dermatitis atopic	10.2% 5/49 • Number of events 5 • Baseline to end of study (up to 5 months)	8.1% 3/37 • Number of events 3 • Baseline to end of study (up to 5 months)	5.3% 2/38 • Number of events 2 • Baseline to end of study (up to 5 months)

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60