A Long-term Study of Baricitinib (LY3009104) With Topical Corticosteroids in Adults With Moderate to Severe Atopic Dermatitis That Are Not Controlled With Cyclosporine or for Those Who Cannot Take Oral Cyclosporine Because it is Not Medically Advisable (BREEZE-AD4)

Lilly

Status and phase: Completed; Phase 3

Conditions: Atopic Dermatitis

Treatments: Drug: Topical corticosteroid; Drug: Placebo; Drug: Baricitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT03428100

16841

I4V-MC-JAIN (Other Identifier)

2017-004574-34 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to determine the efficacy and safety of baricitinib in combination with topical corticosteroids in participants with moderate to severe atopic dermatitis who have experienced failure to cyclosporine or are intolerant to, or have contraindication to cyclosporine.

Enrollment: 463 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have been diagnosed with moderate to severe Atopic Eczema (Atopic Dermatitis) for at least 12 months.
• Have had inadequate response 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 during a washout period).
• Agree to use emollients daily.
• Have a medical contraindication to cyclosporine, or had intolerance and/or unacceptable toxicity or inadequate response to cyclosporine in the past.

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 are 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 prior to randomization.
  • Received prior treatment with any oral Janus kinase (JAK) inhibitor less than 4 weeks prior to randomization.
  • Received oral corticosteroids within 4 weeks prior to randomization or parenteral corticosteroids administered by intramuscular or intravenous (IV) injection within 2 weeks prior to study entry or within 6 weeks prior to planned randomization or are anticipated to require parenteral injection of corticosteroids during the study.
  • Have had an intra-articular corticosteroid injection within 2 weeks prior to study entry or within 6 weeks prior to planned randomization.

• 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: venous thromboembolic event (VTE), myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage III/IV heart failure.

• Have a history of recurrent (≥ 2) VTE or are considered at high risk of VTE as deemed by the investigator.

• 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 and/or clinically serious viral, bacterial, fungal, or parasitic infection including but not limited to herpes zoster, tuberculosis.

• Have specific laboratory abnormalities related to thyroid, renal and liver function, or blood cells.

• Have received certain treatments that are contraindicated.

• Pregnant or breastfeeding.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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463 participants in 19 patient groups, including a placebo group

4 mg Baricitinib

Experimental group

Description:

4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Treatment:

Drug: Baricitinib

Drug: Placebo

Drug: Topical corticosteroid

2 mg Baricitinib

Experimental group

Description:

2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Treatment:

Drug: Baricitinib

Drug: Placebo

Drug: Topical corticosteroid

1 mg Baricitinib

Experimental group

Description:

1 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Treatment:

Drug: Baricitinib

Drug: Placebo

Drug: Topical corticosteroid

Placebo

Placebo Comparator group

Description:

Placebo administered orally once daily in combination with topical corticosteroids. Additional Placebo administered orally to maintain the blind.

Treatment:

Drug: Placebo

Drug: Topical corticosteroid

Long Term Extension(LTE) Substudy 4mg Baricitinib to 4mg Baricitinib (Responders/Partial Responders)

Experimental group

Description:

4 mg Baricitinib administered orally once daily (continued previous dose) in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Treatment:

Drug: Baricitinib

Drug: Placebo

Drug: Topical corticosteroid

LTE Substudy 4 mg Baricitinib to 2 mg Baricitinib (Responders/Partial Responders)

Experimental group

Description:

4 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Treatment:

Drug: Baricitinib

Drug: Placebo

Drug: Topical corticosteroid

LTE Substudy 2 mg Baricitinib to 2 mg Baricitinib (Responders/Partial Responders)

Experimental group

Description:

2 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Treatment:

Drug: Baricitinib

Drug: Placebo

Drug: Topical corticosteroid

LTE Substudy 2 mg Baricitinib to 1 mg Baricitinib (Responders/Partial Responders)

Experimental group

Description:

2 mg Baricitinib rerandomized to 1 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Treatment:

Drug: Baricitinib

Drug: Placebo

Drug: Topical corticosteroid

LTE 4 mg Baricitinib (Responders/Partial Responders) - Did Not Enter Substudy

Experimental group

Description:

4 mg Baricitinib administered orally once daily (continued previous dose) in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Treatment:

Drug: Baricitinib

Drug: Placebo

Drug: Topical corticosteroid

LTE 2 mg Baricitinib (Responders/Partial Responders) - Did Not Enter Substudy

Experimental group

Description:

2 mg Baricitinib administered orally once daily (continued previous dose) in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Treatment:

Drug: Baricitinib

Drug: Placebo

Drug: Topical corticosteroid

LTE 1 mg Baricitinib (Responders/Partial Responders) - Did Not Enter Substudy

Experimental group

Description:

1 mg administered orally once daily (continued previous dose) in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Treatment:

Drug: Baricitinib

Drug: Placebo

Drug: Topical corticosteroid

LTE Placebo (Responders/Partial Responders) - Did Not Enter Substudy

Placebo Comparator group

Description:

Placebo administered orally once daily (continued previous dose) in combination with topical corticosteroids. Additional placebo administered orally to maintain the blind.

Treatment:

Drug: Placebo

Drug: Topical corticosteroid

LTE 4 mg Baricitinib (Non-responders) - Did Not Enter Substudy

Experimental group

Description:

4 mg administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Treatment:

Drug: Baricitinib

Drug: Placebo

Drug: Topical corticosteroid

LTE 2 mg Baricitinib to 2 mg Baricitinib (Non-responders) - Did Not Enter Substudy

Experimental group

Description:

2 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Treatment:

Drug: Baricitinib

Drug: Placebo

Drug: Topical corticosteroid

LTE 2 mg Baricitinib to 4 mg Baricitinib (Non-responders) - Did Not Enter Substudy

Experimental group

Description:

2 mg Baricitinib rerandomized to 4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Treatment:

Drug: Baricitinib

Drug: Placebo

Drug: Topical corticosteroid

LTE 1 mg Baricitinib to 2 mg Baricitinib (Non-responders) - Did Not Enter Substudy

Experimental group

Description:

1 mg Baricitinib rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Treatment:

Drug: Baricitinib

Drug: Placebo

Drug: Topical corticosteroid

LTE 1 mg Baricitinib to 4 mg Baricitinib (Non-responders) - Did Not Enter Substudy

Experimental group

Description:

1 mg Baricitinib rerandomized to 4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Treatment:

Drug: Baricitinib

Drug: Placebo

Drug: Topical corticosteroid

LTE Placebo to 2 mg Baricitinib (Non-responders) - Did Not Enter Substudy

Experimental group

Description:

Placebo rerandomized to 2 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Treatment:

Drug: Baricitinib

Drug: Placebo

Drug: Topical corticosteroid

LTE Placebo to 4 mg Baricitinib (Non-responders) - Did Not Enter Substudy

Experimental group

Description:

Placebo rerandomized to 4 mg Baricitinib administered orally once daily in combination with topical corticosteroids. Placebo administered orally to maintain the blind.

Treatment:

Drug: Baricitinib

Drug: Placebo

Drug: Topical corticosteroid