Evaluation of the Efficacy and Safety of Lebrikizumab (LY3650150) in Moderate to Severe Atopic Dermatitis (ADvocate1)

Lilly

Status and phase: Completed; Phase 3

Conditions: Atopic Dermatitis

Treatments: Biological: Lebrikizumab; Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04146363

2019-002932-10 (EudraCT Number)

17801

DRM06-AD04 (Other Identifier)

J2T-DM-KGAB (Other Identifier)

Details and patient eligibility

About

This is a randomized, double-blind, placebo-controlled, parallel-group study which is 52 weeks in duration. The study is designed to confirm the safety and efficacy of lebrikizumab as monotherapy for treatment of moderate-to-severe atopic dermatitis utilizing a 16-week induction treatment period and a 36-week long-term maintenance treatment period.

Enrollment: 424 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female adults and adolescents (≥12 years and ≥40 kg)
• Chronic atopic dermatitis (according to American Academy of Dermatology Consensus Criteria) that has been present for ≥1 year before the screening visit
• Eczema Area and Severity Index (EASI) score ≥16 at the baseline visit
• Investigator Global Assessment (IGA) score ≥3 (scale of 0 to 4) at the baseline visit
• ≥10% body surface area (BSA) of atopic dermatitis involvement at the baseline visit
• History of inadequate response to treatment with topical medications; or determination that topical treatments are otherwise medically inadvisable

Exclusion criteria

• Prior treatment with dupilumab or tralokinumab

• Treatment with topical corticosteroids, calcineurin inhibitors or phosphodiesterase-4 inhibitors such as crisaborole within 1 week prior to the baseline visit

• Treatment with any of the following agents within 4 weeks prior to the baseline visit:

  • Immunosuppressive/immunomodulating drugs (e.g., systemic corticosteroids, cyclosporine, mycophenolate-mofetil, IFN-γ, Janus kinase inhibitors, azathioprine, methotrexate, etc.)
  • Phototherapy and photochemotherapy (PUVA) for AD

• Treatment with the following prior to the baseline visit:

  • An investigational drug within 8 weeks or within 5 half-lives (if known) of baseline, whichever is longer
  • Cell-depleting biologics, including to rituximab, within 6 months of baseline
  • Other biologics within 5 half-lives (if known) or 16 weeks of baseline, whichever is longer

• Treatment with a live (attenuated) vaccine within 12 weeks of the baseline visit or planned during the study

• Uncontrolled chronic disease that might require bursts of oral corticosteroids, e.g., co-morbid severe uncontrolled asthma

• Evidence of active acute or chronic hepatitis

• History of human immunodeficiency virus (HIV) infection or positive HIV serology

• History of malignancy, including mycosis fungoides, within 5 years before the screening visit, except completely treated in situ carcinoma of the cervix, completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin

• Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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424 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Induction Period (Baseline-Week 16): Two subcutaneous (SC) injections of Placebo as a loading dose at Baseline and Week 2 followed by a single injection every 2 weeks (Q2W) from Week 4 until Week 14. Maintenance Period (Week 16-Week 52): Two placebo SC injections as loading dose on Week 16 and Week 18. One placebo SC injection Q2W until Week 50.

Treatment:

Other: Placebo

Lebrikizumab 250 Q2W

Experimental group

Description:

Induction Period (Baseline-Week 16): 500 milligram (mg) Lebrikizumab (2 x 250 mg) SC injections as a loading dose at Baseline and Week 2 visits followed by a single 250 mg Lebrikizumab injection Q2W from Week 4 until Week 14. Maintenance Period (Week 16-Week 52): One 250 mg Lebrikizumab SC injection Q2W until Week 50. For participants who received placebo in the Induction Period, the maintenance loading dose is: Two 250 mg Lebrikizumab SC injections on Week 16. Two 250 mg Lebrikizumab SC injections on Week 18. To maintain the blind, for participants who received Lebrikizumab in the Induction Period, the maintenance loading dose is: One 250 mg Lebrikizumab SC injection and one placebo SC injection on Week 16. One 250 mg Lebrikizumab SC injection and one placebo SC injection on Week 18.

Treatment:

Other: Placebo

Biological: Lebrikizumab

Lebrikizumab 250 Q4W

Experimental group

Description:

Maintenance Period (Week 16-Week 52): One 250 mg Lebrikizumab SC injection every 4 weeks (Q4W) on Weeks 20, 24, 28, 32, 36, 40, 44, and 48. One placebo SC injection Q4W on Weeks 22, 26, 30, 34, 38, 42, 46, and 50. For participants who received placebo in the Induction Period, the maintenance loading dose is: Two 250 mg Lebrikizumab SC injections on Week 16. Two placebo injections on Week 18. To maintain the blind, for participants who received Lebrikizumab in the Induction Period, the maintenance loading dose is: One 250 mg Lebrikizumab SC injection and one placebo SC injection on Week 16. Two placebo injections on Week 18

Treatment:

Other: Placebo

Biological: Lebrikizumab

Escape Arm (Lebrikizumab Q2W)

Experimental group

Description:

Maintenance Period (Week 16-Week 52): Blinded loading doses based on prior treatment assignment will be administered, followed by one 250 mg Lebrikizumab SC injection Q2W until Week 50 in an open-label fashion. For participants who received placebo in the Induction Period, the loading dose is: Two 250 mg Lebrikizumab SC injections on Week 16. Two 250 mg Lebrikizumab SC injections on Week 18. To maintain the loading dose blind, for participants who received Lebrikizumab in the Induction Period, the loading dose is: One 250 mg Lebrikizumab SC injection and one placebo SC injection on Week 16. One 250 mg Lebrikizumab SC injection and one placebo SC injection on Week 18. For participants who do not maintain an acceptable response during the Maintenance Period and entered the Escape Arm, the loading doses will be administrated at entry and 2 weeks after entry based on the treatment assignment prior to entering escape arm.

Treatment:

Other: Placebo

Biological: Lebrikizumab