A Randomized, Double-blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Lebrikizumab in Patients With Moderate to Severe Atopic Dermatitis
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Eli Lilly and Company
- Enrollment
- 424
- Locations
- 94
- Primary Endpoint
- Percentage of Participants With an Investigator Global Assessment (IGA) Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Double-blind
Eligibility Criteria
- Ages
- 12 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Placebo
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.
Intervention: Placebo (Other)
Lebrikizumab 250 Q2W
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.
Intervention: Placebo (Other)
Lebrikizumab 250 Q4W
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
Intervention: Placebo (Other)
Escape Arm (Lebrikizumab Q2W)
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.
Intervention: Placebo (Other)
Lebrikizumab 250 Q2W
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.
Intervention: Lebrikizumab (Biological)
Escape Arm (Lebrikizumab Q2W)
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.
Intervention: Lebrikizumab (Biological)
Lebrikizumab 250 Q4W
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
Intervention: Lebrikizumab (Biological)
Outcomes
Primary Outcomes
Percentage of Participants With an Investigator Global Assessment (IGA) Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16
Time Frame: Baseline to 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.
Percentage of Participants Achieving Eczema Area And Severity Index (EASI-75) (≥75% Reduction in EASI Score) From Baseline to Week 16
Time Frame: Baseline to Week 16
The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent, i.e., percentage of skin 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-75 score was obtained by weight-averaging these 4 scores and will range from 0 (none) to 72 (severe). The EASI-75 responder is defined as a participant who achieves a ≥ 75% improvement from baseline in the EASI score.
Secondary Outcomes
- Percent Change in Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16(Baseline, Week 16)
- Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 4(Baseline to Week 4)
- Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16 in Adults(Baseline to Week 16)
- Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 2(Baseline to Week 2)
- Percentage of Participants With a DLQI Total Score of ≥4-point at Baseline Achieving ≥4-point Improvement in DLQI From Baseline to Week 16(Baseline to Week 16)
- Percentage of Participants With a Sleep-loss Score ≥2 Points at Baseline Who Achieve a ≥2 Points Reduction From Baseline at Week 16(Baseline to Week 16)
- Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1(Baseline to Week 1)
- Percentage of Participants From Those With a Pruritus NRS of ≥4-points at Baseline Re-randomized Having Achieved ≥4-point Reduction From Baseline at Week 16 Who Continue to Exhibit ≥4-point Reduction From Baseline at Week 52(Baseline to Week 52)
- Percentage of Participants Achieving EASI-90 (≥90% Reduction in EASI Score) From Baseline to Week 16(Baseline to Week 16)
- Percentage of Participants With a Pruritus NRS Score of ≥5-points at Baseline Who Achieve a ≥4-point Reduction in Pruritus NRS Score From Baseline to Week 16(Baseline to Week 16)
- Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2(Baseline to Week 2)
- Percent Change in SCORing Atopic Dermatitis (SCORAD) From Baseline to Week 16(Baseline, Week 16)
- Percent Change in EASI Score From Baseline to Week 16(Baseline, Week 16)
- Percentage of Participants Achieving EASI-90 From Baseline to Week 4(Baseline to Week 4)
- Percent Change in Sleep-loss Score From Baseline to Week 16(Baseline, Week 16)
- Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4(Baseline to Week 4)
- Pharmacokinetics (PK): Average Serum Concentration of Lebrikizumab at Week 52(Predose: Baseline, Week 4, Week 16, Week 32, Week 52)
- Percentage of Participants With a Pruritus NRS Score of ≥4-points at Baseline Who Achieve a ≥4-point Reduction in Pruritus NRS Score From Baseline to Week 16(Baseline to Week 16)
- Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16(Baseline, Week 16)
- Percentage of Participants Achieving ≥4 Point Improvement in DLQI From Baseline to Week 16(Baseline to Week 16)
- Change From Baseline in Sleep-loss Score at Week 16(Baseline, Week 16)
- Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1(Baseline to Week 1)
- Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2(Baseline to Week 2)
- Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4(Baseline to Week 4)
- Percentage of Participants From Those Re-randomized Having Achieved IGA 0 or 1 and a ≥2-point Improvement From Baseline at Week 16 Who Continue to Exhibit and IGA 0 or 1 and a ≥2-point Improvement From Baseline at Week 52(Baseline to Week 52)
- Change From Baseline in Percent Body Surface Area (BSA) at Week 16(Baseline, Week 16)
- Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) at Week 16 - Health State Index(Baseline, Week 16)
- Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety at Week 16 - Adolescents(Baseline, Week 16)
- Percent Change in SCORAD (Having Achieved EASI-75 at Week 16) From Baseline at Week 52(Baseline, Week 52)
- Change From Baseline in EQ-5D-5L at Week 16 - Visual Analog Scale (VAS)(Baseline, Week 16)
- Change From Baseline in PROMIS Depression at Week 16 - Adults(Baseline, Week 16)
- Percentage of Participants From Those Re-randomized Having Achieved EASI-75 at Week 16 Who Continued to Exhibit EASI-75 at Week 52 (EASI-75 Calculated Relative to Baseline EASI Score)(Baseline to Week 52)
- Percentage of Participants From Those With a Pruritus NRS of ≥5-points at Baseline Re-randomized Having Achieved ≥4-point Reduction From Baseline at Week 16 Who Continue to Exhibit ≥4-point Reduction From Baseline at Week 52(Baseline to Week 52)
- Change From Baseline in PROMIS Depression at Week 16 - Adolescents(Baseline, Week 16)
- Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score at Week 16 in Participants Who Have Self-Reported Comorbid Asthma(Baseline, Week 16)
- Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16(Baseline, Week 16)
- Change From Baseline in PROMIS Anxiety at Week 16 - Adults(Baseline, Week 16)
- Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 16 - Adolescents(Baseline, Week 16)