A Study of Long-term Baricitinib (LY3009104) Therapy in Atopic Dermatitis (BREEZE-AD3)

Lilly

Status and phase: Completed; Phase 3

Conditions: Atopic Dermatitis

Treatments: Drug: Baricitinib; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03334435

I4V-MC-JAHN (Other Identifier)

16587

2017-000873-35 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to evaluate the long-term safety and efficacy of baricitinib in participants with atopic dermatitis.

Participants were enrolled in this study from the originating studies (JAHL, JAHM, JAIY) or were directly enrolled in the open-label arm.

Enrollment: 1,645 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Have participated in previous studies (JAHL, JAHM and JAIY) and met specific completion requirements for those studies, and do not meet any of the following Exclusions:

Exclusion Criteria:

• Had investigational product permanently discontinued at any time during a previous Baricitinib study.
• 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

OR

Have not participated in previous studies (JAHL, JAHM and JAIY) and satisfy the following criteria:

Inclusion Criteria:

• Have been diagnosed with moderate to severe Atopic Dermatitis for at least 12 months.
• 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 during a washout period).
• 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 episode 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 prior to randomization.
  • Received prior treatment with any oral Janus kinase (JAK) inhibitor.
  • Received any 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, chronic liver disease 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,645 participants in 16 patient groups, including a placebo group

Responders and Partial Responders (RPR)-Placebo

Placebo Comparator group

Description:

Responders or partial responders (RPR) \[Investigator's Global Assessment (IGA) of (0,1, or 2) at entry to study JAHN and never rescued in originating study\] participants from previous Baricitinib monotherapy studies-JAHL and JAHM and combination therapy study-JAIY were assigned to remain in this arm to receive placebo orally.

Treatment:

Drug: Placebo

Drug: Baricitinib

RPR-Bari 1-milligram (mg)

Experimental group

Description:

RPR participants from previous Baricitinib monotherapy studies-JAHL and JAHM were assigned to remain in this arm to receive Baricitinib 1 mg orally.

Treatment:

Drug: Baricitinib

RPR-Bari 2-mg

Experimental group

Description:

RPR participants from previous Baricitinib monotherapy studies-JAHL and JAHM and combination therapy study-JAIY were assigned to remain in this arm to receive Baricitinib 2 mg orally.

Treatment:

Drug: Baricitinib

RPR-Bari 4-mg

Experimental group

Description:

RPR participants from previous Baricitinib monotherapy studies-JAHL and JAHM and combination therapy study-JAIY were assigned to remain in this arm to receive Baricitinib 4 mg orally.

Treatment:

Drug: Baricitinib

Non-responders (NR): Bari 1 mg to 2 mg

Experimental group

Description:

Non-responder (NR) \[those not meeting definition of RPR\] participants from previous Baricitinib monotherapy studies-JAHL and JAHM who received Baricitinib 1 mg and were re-randomized to this arm to receive Baricitinib 2 mg orally.

Treatment:

Drug: Baricitinib

NR: Bari 1 mg to 4 mg

Experimental group

Description:

NR participants from previous Baricitinib monotherapy studies-JAHL and JAHM who received Baricitinib 1 mg and were re-randomized to this arm to receive Baricitinib 4 mg orally.

Treatment:

Drug: Baricitinib

NR: Bari 2 mg to 2 mg

Experimental group

Description:

NR participants from previous Baricitinib monotherapy studies-JAHL and JAHM and combination therapy study-JAIY who received Baricitinib 2 mg and were re-randomized to this arm to receive Baricitinib 2 mg orally.

Treatment:

Drug: Baricitinib

NR: Bari 2 mg to 4 mg

Experimental group

Description:

NR participants from previous Baricitinib monotherapy studies-JAHL and JAHM and combination therapy study-JAIY who received Baricitinib 2 mg and were re-randomized to this arm to receive Baricitinib 4 mg orally.

Treatment:

Drug: Baricitinib

NR: Bari 4 mg to 4 mg

Experimental group

Description:

NR participants from previous Baricitinib monotherapy studies-JAHL and JAHM and combination therapy study-JAIY who received Baricitinib 4 mg and were re-randomized to this arm to receive Baricitinib 4 mg orally.

Treatment:

Drug: Baricitinib

NR: Placebo to Bari 2 mg

Experimental group

Description:

NR participants from previous Baricitinib monotherapy studies-JAHL and JAHM and combination therapy study-JAIY who received placebo and were re-randomized to this arm to receive Baricitinib 2 mg orally.

Treatment:

Drug: Placebo

Drug: Baricitinib

NR: Placebo to Bari 4 mg

Experimental group

Description:

NR participants from previous Baricitinib monotherapy studies-JAHL and JAHM and combination therapy study-JAIY who received placebo and were re-randomized to this arm to receive Baricitinib 4 mg orally.

Treatment:

Drug: Placebo

Drug: Baricitinib

Placebo

Placebo Comparator group

Description:

Participants from previous Baricitinib monotherapy studies (JAHL, JAHM) and combination therapy study (JAIY) were randomized or assigned to this arm to receive placebo orally.

Treatment:

Drug: Placebo

Bari 1 mg

Experimental group

Description:

Participants from previous Baricitinib monotherapy studies (JAHL, JAHM) were randomized or assigned to this arm to receive Baricitinib 1 mg orally.

Treatment:

Drug: Baricitinib

Bari 2 mg

Experimental group

Description:

Participants from previous Baricitinib monotherapy studies (JAHL, JAHM) and combination therapy study (JAIY) were randomized or assigned to this arm to receive Baricitinib 2 mg orally.

Treatment:

Drug: Baricitinib

Bari 4 mg

Experimental group

Description:

Participants from previous Baricitinib monotherapy studies (JAHL, JAHM) and combination therapy study (JAIY) were randomized or assigned to this arm to receive Baricitinib 4 mg orally.

Treatment:

Drug: Baricitinib

Bari 2-mg Open-Label Addendum

Experimental group

Description:

Participants were directly enrolled to this open-label arm to receive Baricitinib 2-mg orally.

Treatment:

Drug: Baricitinib