Atopic Dermatitis
Conditions
Keywords
eczema, atopic eczema
Brief summary
This open-label study will evaluate the long-term efficacy and safety of baricitinib in adult participants with moderate to severe atopic dermatitis (AD).
Interventions
DRUGBaricitinib
Administered orally
Sponsors
Incyte Corporation
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Have participated in Study JAIW (NCT03435081), and meet specific completion requirements for that study, and do not meet any of the following Exclusions: * Have significant uncontrolled cerebro-cardiovascular (e.g., myocardial infarction \[MI\], unstable angina, unstable arterial hypertension, severe heart failure, or cerebrovascular accident), respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, neuropsychiatric disorders, or abnormal laboratory values that developed during a previous baricitinib study that, in the opinion of the investigator, pose an unacceptable risk to the participant if investigational product continues to be administered. * Have a known hypersensitivity to baricitinib or any component of this investigational product. * Had investigational product permanently discontinued at any time during a previous baricitinib study, except for participants who had investigational product discontinued during originating study because of rescue with an oral systemic AD therapy (e.g., corticosteroid, cyclosporine, methotrexate). * Had temporary investigational product interruption continue at the final study visit of a previous baricitinib study and, in the opinion of the investigator, this poses an unacceptable risk for the participant's participation in the study. * Pregnant or breastfeeding OR • Have not participated in a Study JAIW (NCT03435081) and satisfy the following criteria: Inclusion Criteria: * Have a diagnosis of atopic dermatitis (AD) at least 12 months before screening. * Have moderate to severe AD, including all of the following: * EASI score ≥16 * IGA score of ≥3 * 10%- 50% 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) * 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 episodes 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). * 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, 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) | 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. The results were analyzed using non-responder imputation (NRI). All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as EASI75. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 | Week 16 | 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. The results were analyzed using NRI. All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as IGA 0/1. |
| Percentage of Participants Achieving a Body Surface Area (BSA) of ≤3% | Week 16 | The BSA affected by AD will be assessed for 4 separate body regions: 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. BSA was calculated using the participant's palm using the 1% rule, 1 palm was equivalent to 1% with estimates of the number of palms it takes to cover the affected AD area. Maximum number of palms were 10 palms for head and neck (10%), 20 palms for upper extremities (20%), 30 palms for trunk, including axilla and groin (30%), 40 palms for lower extremities, including buttocks (40%). Percent of BSA for a body region was calculated as = total number of palms in a body region \* % surface area equivalent to 1 palm. Overall percent BSA of all 4 body regions ranges from 0% to 100 % with higher values representing greater severity of AD. |
| Percentage of Participants Achieving a ≥4-Point Improvement in Itch Numeric Rating Scale (NRS) | Week 16 | The 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 selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours. |
Countries
Canada, Puerto Rico, United States
Participant flow
Recruitment details
Eligible participants (nonresponder/partial responder: completed at least 16 weeks of treatment; responder: completed the full treatment period) from originating study JAIW (NCT03435081) enrolled into Open-label Treatment Period of JAIX \[lasting from Week 0 (baseline through Week 200) or early termination visit\]. Participants enrolled directly into Protocol Addendum I4V-MC-JAIX (2) without first completing at least 16 weeks of treatment in originating study JAIW.
Participants by arm
| Arm | Count |
|---|---|
| Placebo/Baricitinib 2-mg Open-label 2 mg baricitinib administered orally QD to participants who randomized to placebo in the originating study (JAIW). | 117 |
| Baricitinib 1-mg/Baricitinib 2-mg Open-label 2 mg baricitinib administered orally QD to participants who randomized to 1 mg baricitinib in the originating study (JAIW). | 119 |
| Baricitinib 2-mg/Baricitinib 2-mg Open-label 2 mg baricitinib administered orally QD to participants who randomized to 2 mg baricitinib in the originating study (JAIW). | 108 |
| Baricitinib 2-mg Open-Label Addendum Participants were directly enrolled to receive open-label 2 mg baricitinib orally QD. | 30 |
| Total | 374 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 5 | 3 | 0 |
| Overall Study | Death | 0 | 2 | 0 | 0 |
| Overall Study | Lack of Efficacy | 34 | 52 | 37 | 2 |
| Overall Study | Lost to Follow-up | 16 | 4 | 12 | 3 |
| Overall Study | Physician Decision | 3 | 2 | 1 | 0 |
| Overall Study | Pregnancy | 0 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 2 | 0 |
| Overall Study | Sponsor Decision | 38 | 31 | 35 | 18 |
| Overall Study | Withdrawal by Subject | 19 | 21 | 18 | 7 |
Baseline characteristics
| Characteristic | Total | Baricitinib 1-mg/Baricitinib 2-mg | Baricitinib 2-mg/Baricitinib 2-mg | Baricitinib 2-mg Open-Label Addendum | Placebo/Baricitinib 2-mg |
|---|---|---|---|---|---|
| Age, Continuous | 40.30 years STANDARD_DEVIATION 16.41 | 40.70 years STANDARD_DEVIATION 16.86 | 39.30 years STANDARD_DEVIATION 15.05 | 43.80 years STANDARD_DEVIATION 17.67 | 39.90 years STANDARD_DEVIATION 16.87 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 59 Participants | 13 Participants | 19 Participants | 10 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 309 Participants | 105 Participants | 87 Participants | 20 Participants | 97 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 6 Participants | 2 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 74 Participants | 24 Participants | 19 Participants | 4 Participants | 27 Participants |
| Race (NIH/OMB) Black or African American | 61 Participants | 15 Participants | 22 Participants | 4 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 15 Participants | 5 Participants | 4 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 215 Participants | 72 Participants | 60 Participants | 22 Participants | 61 Participants |
| Region of Enrollment Canada | 105 participants | 38 participants | 31 participants | 0 participants | 36 participants |
| Region of Enrollment United States | 269 participants | 81 participants | 77 participants | 30 participants | 81 participants |
| Sex: Female, Male Female | 188 Participants | 60 Participants | 57 Participants | 16 Participants | 55 Participants |
| Sex: Female, Male Male | 186 Participants | 59 Participants | 51 Participants | 14 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 117 | 2 / 119 | 0 / 108 | 0 / 29 |
| other Total, other adverse events | 35 / 117 | 22 / 119 | 28 / 108 | 2 / 29 |
| serious Total, serious adverse events | 8 / 117 | 8 / 119 | 10 / 108 | 0 / 29 |
Outcome results
Primary
Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75)
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. The results were analyzed using non-responder imputation (NRI). All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as EASI75.
Time frame: Week 16
Population: mITT population included all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Baricitinib 2-mg | Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) | 59.0 percentage of participants |
| Baricitinib 1-mg/Baricitinib 2-mg | Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) | 40.3 percentage of participants |
| Baricitinib 2-mg/Baricitinib 2-mg | Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) | 45.4 percentage of participants |
| Baricitinib 2-mg Open-Label Addendum | Percentage of Participants Achieving Eczema Area and Severity Index 75 (EASI75) | 50.0 percentage of participants |
Secondary
Percentage of Participants Achieving a ≥4-Point Improvement in Itch Numeric Rating Scale (NRS)
The 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 selecting the number, using a daily diary, that best describes the worst level of itching in the past 24 hours.
Time frame: Week 16
Population: mITT population included all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Baricitinib 2-mg | Percentage of Participants Achieving a ≥4-Point Improvement in Itch Numeric Rating Scale (NRS) | 41.9 percentage of participants |
| Baricitinib 1-mg/Baricitinib 2-mg | Percentage of Participants Achieving a ≥4-Point Improvement in Itch Numeric Rating Scale (NRS) | 29.4 percentage of participants |
| Baricitinib 2-mg/Baricitinib 2-mg | Percentage of Participants Achieving a ≥4-Point Improvement in Itch Numeric Rating Scale (NRS) | 30.6 percentage of participants |
| Baricitinib 2-mg Open-Label Addendum | Percentage of Participants Achieving a ≥4-Point Improvement in Itch Numeric Rating Scale (NRS) | 26.7 percentage of participants |
Secondary
Percentage of Participants Achieving a Body Surface Area (BSA) of ≤3%
The BSA affected by AD will be assessed for 4 separate body regions: 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. BSA was calculated using the participant's palm using the 1% rule, 1 palm was equivalent to 1% with estimates of the number of palms it takes to cover the affected AD area. Maximum number of palms were 10 palms for head and neck (10%), 20 palms for upper extremities (20%), 30 palms for trunk, including axilla and groin (30%), 40 palms for lower extremities, including buttocks (40%). Percent of BSA for a body region was calculated as = total number of palms in a body region \* % surface area equivalent to 1 palm. Overall percent BSA of all 4 body regions ranges from 0% to 100 % with higher values representing greater severity of AD.
Time frame: Week 16
Population: mITT population included all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Baricitinib 2-mg | Percentage of Participants Achieving a Body Surface Area (BSA) of ≤3% | 39.3 percentage of participants |
| Baricitinib 1-mg/Baricitinib 2-mg | Percentage of Participants Achieving a Body Surface Area (BSA) of ≤3% | 21.8 percentage of participants |
| Baricitinib 2-mg/Baricitinib 2-mg | Percentage of Participants Achieving a Body Surface Area (BSA) of ≤3% | 35.2 percentage of participants |
| Baricitinib 2-mg Open-Label Addendum | Percentage of Participants Achieving a Body Surface Area (BSA) of ≤3% | 43.3 percentage of participants |
Secondary
Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1
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. The results were analyzed using NRI. All participants who either discontinued the study treatment or discontinued the study for any reason at any time were defined as non-responders for the NRI analysis for categorical variables such as IGA 0/1.
Time frame: Week 16
Population: mITT population included all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo/Baricitinib 2-mg | Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 | 44.4 percentage of participants |
| Baricitinib 1-mg/Baricitinib 2-mg | Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 | 18.5 percentage of participants |
| Baricitinib 2-mg/Baricitinib 2-mg | Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 | 29.6 percentage of participants |
| Baricitinib 2-mg Open-Label Addendum | Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 | 40.0 percentage of participants |