Atopic Dermatitis
Conditions
Keywords
Atopic Eczema
Brief summary
The purpose of this study is to evaluate the safety and effectiveness of Baricitinib in eczema.
Interventions
DRUGBaricitinib
Administered orally
DRUGPlacebo
Administered orally
Administered topically
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have moderate-to-severe Atopic Dermatitis (AD), as determined by all of the following: 1. EASI of 12 or more 2. Greater than or equal to 10% of body surface area involvement 3. Diagnosed with AD at least 2 years prior * Have a history of inadequate clinical response to other eczema treatments
Exclusion criteria
* Females who are pregnant or nursing * Participants who do not agree to use adequate contraception * Are currently experiencing or have a history of: * Skin conditions such as psoriasis or lupus erythematosus * Skin disease that requires frequent hospitalizations or intravenous treatment * Compromised immunity * Serious illness that could interfere with study participation, or a clinically important deviation in physical examination, vital sign measurements, electrocardiograms, or abnormalities on laboratory tests * Currently experiencing or have a history of: * Active or latent Tuberculosis or specific immunity disorders and infections * Malignancy or lymphoproliferative diseases in the last 5 years (or cervical, basal or squamous skin cancer re-occurrence in the last 3 years) * Human Immunodeficiency Virus (HIV) * Hepatitis B, Hepatitis C, or chronic liver disease * Have received certain types of vaccinations
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a 50% or Greater Reduction in the Eczema Area and Severity Index (EASI 50) | Week 16 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in the EASI at Week 16 | Baseline, Week 16 | 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. |
| Change From Baseline in the Scoring Atopic Dermatitis (SCORAD) at Week 16 | Baseline, Week 16 | 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. |
| Change From Baseline in the Investigator's Global Assessment (IGA) at Week 16 | Baseline, 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). |
| Change From Baseline in the EASI at Week 16 | Baseline, Week 16 | 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. |
| Change From Baseline in the Itch Numerical Rating Scale (NRS) at Week 16 | Baseline, Week 16 | 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. |
| Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Baricitinib | 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. | Pharmacokinetics (PK): Maximum serum concentration (Cmax) of Baricitinib |
| Change From Baseline in the Dermatologic Life Quality Index (DLQI) at Week 16 | 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. 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. |
Countries
Japan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo administered orally (PO) once daily (QD), for 16 weeks Triamcinolone 0.1% applied topically also permitted throughout study. | 49 |
| 2 mg Baricitinib 2mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study. | 37 |
| 4mg Baricitinib 4mg Baricitinib administered PO QD for 16 weeks. Triamcinolone 0.1% applied topically also permitted throughout study. | 38 |
| Total | 124 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 3 | 6 |
| Overall Study | Lack of Efficacy | 9 | 4 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 | 1 |
| Overall Study | Met Exclusion Criteria | 0 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 2 | 4 |
Baseline characteristics
| Characteristic | Total | 4mg Baricitinib | 2 mg Baricitinib | Placebo |
|---|---|---|---|---|
| Age, Continuous | 37.8 years STANDARD_DEVIATION 14.03 | 36.4 years STANDARD_DEVIATION 14.47 | 40.0 years STANDARD_DEVIATION 14.38 | 37.3 years STANDARD_DEVIATION 13.49 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 6 Participants | 4 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 110 Participants | 32 Participants | 33 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Median EASI Total Score | 21.2 units on a scale | 19.5 units on a scale | 22.1 units on a scale | 22.1 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 33 Participants | 9 Participants | 8 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 25 Participants | 9 Participants | 9 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 61 Participants | 18 Participants | 20 Participants | 23 Participants |
| Region of Enrollment Japan | 20 Participants | 6 Participants | 6 Participants | 8 Participants |
| Region of Enrollment United States | 105 Participants | 32 Participants | 31 Participants | 42 Participants |
| Sex: Female, Male Female | 56 Participants | 16 Participants | 15 Participants | 25 Participants |
| Sex: Female, Male Male | 68 Participants | 22 Participants | 22 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 37 | 0 / 38 |
| other Total, other adverse events | 14 / 49 | 13 / 37 | 19 / 38 |
| serious Total, serious adverse events | 0 / 49 | 2 / 37 | 1 / 38 |
Outcome results
Primary
Percentage of Participants With a 50% or Greater Reduction in the Eczema Area and Severity Index (EASI 50)
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.
Time frame: Week 16
Population: All participants who received at least one dose of study drug and had EASI 50 data at Week 16.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a 50% or Greater Reduction in the Eczema Area and Severity Index (EASI 50) | 37 percentage of participants |
| 2 mg Baricitinib | Percentage of Participants With a 50% or Greater Reduction in the Eczema Area and Severity Index (EASI 50) | 57 percentage of participants |
| 4mg Baricitinib | Percentage of Participants With a 50% or Greater Reduction in the Eczema Area and Severity Index (EASI 50) | 61 percentage of participants |
p-value: =0.065Chi-squared
p-value: =0.027Chi-squared
Secondary
Change From Baseline in the Dermatologic Life Quality Index (DLQI) at 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. 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.
Time frame: Baseline, Week 16
Population: All participants who have received at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Dermatologic Life Quality Index (DLQI) at Week 16 | -6.27 units on a scale | Standard Error 0.82 |
| 2 mg Baricitinib | Change From Baseline in the Dermatologic Life Quality Index (DLQI) at Week 16 | -6.89 units on a scale | Standard Error 0.89 |
| 4mg Baricitinib | Change From Baseline in the Dermatologic Life Quality Index (DLQI) at Week 16 | -7.96 units on a scale | Standard Error 0.86 |
Secondary
Change From Baseline in the EASI at Week 16
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.
Time frame: Baseline, Week 16
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the EASI at Week 16 | -10.84 units on a scale | Standard Error 1.62 |
| 2 mg Baricitinib | Change From Baseline in the EASI at Week 16 | -16.44 units on a scale | Standard Error 1.72 |
| 4mg Baricitinib | Change From Baseline in the EASI at Week 16 | -16.04 units on a scale | Standard Error 1.72 |
Secondary
Change From Baseline in the Investigator's Global Assessment (IGA) 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).
Time frame: Baseline, Week 16
Population: All participants who received at least one dose of study drug and had IGA data at Week 16 .
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Investigator's Global Assessment (IGA) at Week 16 | -0.9 units on a scale | Standard Deviation 0.69 |
| 2 mg Baricitinib | Change From Baseline in the Investigator's Global Assessment (IGA) at Week 16 | -1.4 units on a scale | Standard Deviation 1.31 |
| 4mg Baricitinib | Change From Baseline in the Investigator's Global Assessment (IGA) at Week 16 | -1.3 units on a scale | Standard Deviation 1.01 |
Secondary
Change From Baseline in the Itch Numerical Rating Scale (NRS) at Week 16
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.
Time frame: Baseline, Week 16
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Itch Numerical Rating Scale (NRS) at Week 16 | -1.72 units on a scale | Standard Error 0.44 |
| 2 mg Baricitinib | Change From Baseline in the Itch Numerical Rating Scale (NRS) at Week 16 | -2.61 units on a scale | Standard Error 0.47 |
| 4mg Baricitinib | Change From Baseline in the Itch Numerical Rating Scale (NRS) at Week 16 | -2.22 units on a scale | Standard Error 0.46 |
Secondary
Change From Baseline in the Scoring Atopic Dermatitis (SCORAD) at Week 16
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.
Time frame: Baseline, Week 16
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Scoring Atopic Dermatitis (SCORAD) at Week 16 | -11.89 units on a scale | Standard Error 2.88 |
| 2 mg Baricitinib | Change From Baseline in the Scoring Atopic Dermatitis (SCORAD) at Week 16 | -23.87 units on a scale | Standard Error 3.03 |
| 4mg Baricitinib | Change From Baseline in the Scoring Atopic Dermatitis (SCORAD) at Week 16 | -26.54 units on a scale | Standard Error 2.97 |
Secondary
Percentage Change From Baseline in the EASI at Week 16
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.
Time frame: Baseline, Week 16
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage Change From Baseline in the EASI at Week 16 | -45.87 units on a scale | Standard Error 5.85 |
| 2 mg Baricitinib | Percentage Change From Baseline in the EASI at Week 16 | -64.19 units on a scale | Standard Error 6.2 |
| 4mg Baricitinib | Percentage Change From Baseline in the EASI at Week 16 | -64.69 units on a scale | Standard Error 6.21 |
Secondary
Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Baricitinib
Pharmacokinetics (PK): Maximum serum concentration (Cmax) of Baricitinib
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Baricitinib | 18.5 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 70 |
| 2 mg Baricitinib | Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Baricitinib | 37.7 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 38.9 |