Dermira, a biopharmaceutical company dedicated to bringing biotech ingenuity to medical dermatology by delivering differentiated, new therapies to the millions of patients living with chronic skin conditions, announced the initiation of a phase 2b dose-ranging study evaluating the safety and efficacy of lebrikizumab in adult patients with moderate-to-severe atopic dermatitis, the most common form of eczema. Lebrikizumab is a novel, humanized monoclonal antibody designed to bind to IL-13 with high affinity, specifically preventing heterodimerization of the IL-13/IL-4 receptor and subsequent signaling. IL-13 plays a central role in type 2 inflammation and is an important pathogenic mediator in atopic dermatitis.
“Millions of people suffer from atopic dermatitis, and despite recent treatment advances, additional therapeutic options are needed to safely and effectively manage this chronic skin condition,” said Luis Peña, chief development officer of Dermira. “Based on compelling phase 2 proof-of-concept data in moderate-to-severe atopic dermatitis patients, we look forward to further evaluating lebrikizumab. We believe the phase 2b dose-ranging study, with the introduction of a loading dose, as well as higher dosing regimens, will allow us to optimize the clinical profile of lebrikizumab in patients living with this debilitating condition.”
The randomized, double-blind, placebo-controlled, parallel-group phase 2b study is designed to evaluate the safety and efficacy of lebrikizumab as a monotherapy compared with placebo and to establish the dosing regimen for a potential phase 3 program in patients with moderate-to-severe atopic dermatitis. The study is expected to enroll approximately 275 patients ages 18 years and older with moderate-to-severe atopic dermatitis at sites in the United States. The study will evaluate three active treatment groups compared to a placebo treatment group, for 16 weeks, with patients randomized in a 3:3:3:2 fashion: Treatment Group 1: A loading dose of 250 mg of lebrikizumab at week 0, followed by 125 mg of lebrikizumab every four weeks. Treatment Group 2: A loading dose of 500 mg of lebrikizumab at week 0, followed by 250 mg of lebrikizumab every four weeks. Treatment Group 3: A loading dose of 500 mg of lebrikizumab at each of weeks 0 and 2, followed by 250 mg of lebrikizumab every two weeks. Treatment Group 4: Placebo at week 0 and every two weeks thereafter.
The primary endpoint of the study is the percent change in the Eczema Area Severity Index (EASI) from baseline to week 16. Key secondary endpoints that will be evaluated during the 16-week treatment period include: the proportion of patients with a 75 percent improvement from baseline in EASI (EASI-75); the proportion of patients with an Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) and a reduction of 2 or more points (on a 5-point scale) from baseline; the proportion of patients achieving EASI-50 and EASI-90; and changes in sleep loss and pruritus (itch) scores from baseline, both scored using an 11-point numerical rating scale (NRS). Key inclusion criteria for patients enrolled in this study include chronic atopic dermatitis for at least one year, an EASI score of 16 or greater, an IGA score of 3 or greater, and a body surface area involving at least 10 percent at screening and baseline. Following the end of 16-week treatment period, patients will be followed for an additional 16 weeks.
In January 2018, results from the TREBLE study were accepted and published online in the Journal of the American Academy of Dermatology. TREBLE was a randomized, placebo-controlled, double-blind, Phase 2, proof-of-concept study designed to assess the efficacy and safety of lebrikizumab as add-on therapy to twice daily topical corticosteroids (TCS) for adult patients with moderate-to-severe atopic dermatitis. The study was conducted by F. Hoffmann-La Roche Ltd.
Patients in the TREBLE study were randomized 1:1:1:1 to receive either a single, 125-mg dose of lebrikizumab plus TCS (n=52), a single, 250-mg dose of lebrikizumab plus TCS (n=53), 125 mg of lebrikizumab every four weeks plus TCS (n=51), or placebo every four weeks plus TCS (n=53), for up to 12 weeks. Patients in all treatment groups were required to receive two weeks of twice daily TCS treatment prior to baseline measurement and throughout the 12-week treatment period. The primary endpoint was the percentage of patients achieving EASI-50 at week 12.
After 12 weeks of treatment, significantly more patients achieved EASI-50 with lebrikizumab administered at 125 mg every four weeks (82.4%; p=0.026) compared with placebo (62.3%). Patients who received single dose lebrikizumab showed no statistically significant improvements in EASI-50 compared with placebo.
Lebrikizumab was generally well-tolerated. There were no imbalances in proportions of patients reporting adverse events (AEs), serious adverse events, events leading to discontinuation, or overall infections when comparing all lebrikizumab-treated patients with placebo. Three patients (2.0%) in the lebrikizumab groups (all doses combined) and one patient (2.0%) in the placebo group experienced an AE that led to withdrawal from the study. There were no deaths, anaphylactic reactions, malignancies, or protocol-defined parasitic or targeted intracellular infections of interest. Injection-site reactions occurred infrequently (1.3% in all lebrikizumab groups and 1.9% in the placebo group).
The dose-response relationships observed across multiple endpoints in TREBLE, as well as trends towards improved efficacy with increasing dose and duration, suggest that further increases in the dose and/or treatment duration may result in improved efficacy. Dermira’s phase 2b study will evaluate this.