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NCT03443024

A Study of Lebrikizumab (LY3650150) in Participants With Moderate-to-Severe Atopic Dermatitis

Completed Phase 2 Results posted Last updated 4 May 2021
What this trial tests

Phase 2 trial testing Lebrikizumab in Atopic Dermatitis in 280 participants. Completed in 23 May 2019.

Timeline
30 January 2018
Primary endpoint
7 February 2019
23 May 2019

Quick facts

Lead sponsorEli Lilly and Company
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment280
Start date30 January 2018
Primary completion7 February 2019
Estimated completion23 May 2019
Sites58 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Eli Lilly and Company — full company profile →

Who can join

18 and older, any sex, with Atopic Dermatitis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percent Change From Baseline in Eczema Area and Severity Index (EASI) Primary · Baseline, Week 16

The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs 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 score was obtained by weight-averaging these 4 scores and

GroupValue95% CI
125 mg Lebrikizumab (Q4W)-62.34± 37.266
250 mg Lebrikizumab (Q4W)-69.21± 38.282
250 mg Lebrikizumab (Q2W)-72.09± 37.229
Placebo-41.12± 59.496
Percentage of Participants With a 75% Improvement From Baseline in EASI (EASI75) at Week 16 Secondary · Week 16

The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs 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 score was obtained by weight-averaging these 4 scores and

GroupValue95% CI
125 mg Lebrikizumab (Q4W)43.3
250 mg Lebrikizumab (Q4W)56.1
250 mg Lebrikizumab (Q2W)60.6
Placebo24.3
Percentage of Participants With an Investigator Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) and a Reduction ≥2 Points From Baseline to Week 16 (5-point Scale) Secondary · Week 16

The IGA measures the investigator's global assessment of the participant's overall severity of their 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.

GroupValue95% CI
125 mg Lebrikizumab (Q4W)26.6
250 mg Lebrikizumab (Q4W)33.7
250 mg Lebrikizumab (Q2W)44.6
Placebo15.3
Percentage of Participants With EASI <7 at Week 16 Secondary · Week 16

The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs 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 score was obtained by weight-averaging these 4 scores and

GroupValue95% CI
125 mg Lebrikizumab (Q4W)42.2
250 mg Lebrikizumab (Q4W)61.2
250 mg Lebrikizumab (Q2W)61.8
Placebo29.3
Percentage of Participants Achieving EASI50 at Week 16 Secondary · Week 16

The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs 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 score was obtained by weight-averaging these 4 scores and

GroupValue95% CI
125 mg Lebrikizumab (Q4W)66.4
250 mg Lebrikizumab (Q4W)77.0
250 mg Lebrikizumab (Q2W)81.0
Placebo45.8
Percentage of Participants Achieving EASI90 at Week 16 Secondary · Week 16

The EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs 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 score was obtained by weight-averaging these 4 scores and

GroupValue95% CI
125 mg Lebrikizumab (Q4W)26.1
250 mg Lebrikizumab (Q4W)36.1
250 mg Lebrikizumab (Q2W)44.0
Placebo11.4
Percent Change From Baseline in the Sleep Loss Scale Score Secondary · Baseline, Week 16

The Sleep Loss Scale is used by the participants to report the impact of itching on their sleep every night. Participants responded to the question to what extent did your itching interfere with your sleep last night. The scale ranged from 0 to 4, with 0 (not at all) to 4 (unable to sleep at all). Higher scores indicated a greater impact and worse outcome. Assessments were recorded daily by the participant using an electronic diary. Least Squares (LS) Means were calculated using ANCOVA with the factor of treatment and the baseline sleep-loss scale as covariates.

GroupValue95% CI
125 mg Lebrikizumab (Q4W)-48.68± 50.692
250 mg Lebrikizumab (Q4W)-53.03± 50.662
250 mg Lebrikizumab (Q2W)-64.69± 50.692
Placebo-20.24± 51.066
Percent Change From Baseline in Pruritus Numeric Rating Score (NRS) Secondary · Baseline, Week 16

The Pruritus NRS is an 11-point scale used by participants to assess their worst itch severity over the past 24 hours, with 0 indicating no itch and 10 indicating worst itch imaginable. Pruritus assessments were recorded daily by the participant using an electronic diary. LS Means were calculated using ANCOVA with the factor of treatments and the baseline pruritus NRS as covariates.

GroupValue95% CI
125 mg Lebrikizumab (Q4W)-35.94± 55.553
250 mg Lebrikizumab (Q4W)-49.60± 55.555
250 mg Lebrikizumab (Q2W)-60.63± 55.564
Placebo4.26± 55.610
Percentage of Participants With Pruritus NRS Change of ≥3 at Week 16 Secondary · Week 16

The Pruritus NRS is an 11-point scale used by participants to assess their worst itch severity over the past 24 hours, with 0 indicating no itch and 10 indicating worst itch imaginable. Assessments were recorded daily by the participant using an electronic diary. The percentage of participants who are dichotomized to success (pruritus NRS greater than or equal to 3-point improvement) at Week 16 will be analyzed using a Cochran-Mantel-Haenszel (CMH) test.

GroupValue95% CI
125 mg Lebrikizumab (Q4W)50.9
250 mg Lebrikizumab (Q4W)64.9
250 mg Lebrikizumab (Q2W)76.0
Placebo45.5
Percentage of Participants With Pruritus NRS Change of ≥4 From Baseline to Week 16 Secondary · Week 16

The Pruritus NRS is an 11-point scale used by participants to assess their worst itch severity over the past 24 hours, with 0 indicating no itch and 10 indicating worst itch imaginable. Assessments were recorded daily by the participant using an electronic diary. The percentage of participants who are dichotomized to success (pruritus NRS greater than or equal to 4-point improvement) at Week 16 will be analyzed using a Cochran-Mantel-Haenszel (CMH) test.

GroupValue95% CI
125 mg Lebrikizumab (Q4W)41.8
250 mg Lebrikizumab (Q4W)47.4
250 mg Lebrikizumab (Q2W)70.0
Placebo27.3
Change From Baseline in Body Surface Area (BSA) Involved With Atopic Dermatitis (AD) Secondary · Baseline, Week 16

The body surface area (BSA) affected by AD will be assessed for 4 separate body regions: head and neck, trunk (including genital region), upper extremities, and lower extremities (including the buttocks). Each body region will be assessed for disease extent ranging from 0% to 100% involvement. BSA was calculated using the participant's palm using the 1% rule, 1 palm was equivalent to 1% with estimates of the number of palms it takes to cover the affected AD area. Maximum number of palms were 10 palms for head and neck (10%), 20 palms for upper extremities (20%), 30 palms for trunk, including a

GroupValue95% CI
125 mg Lebrikizumab (Q4W)-19.6± 19.08
250 mg Lebrikizumab (Q4W)-24.9± 20.08
250 mg Lebrikizumab (Q2W)-24.3± 21.00
Placebo-17.4± 20.56
Change From Baseline in Atopic Dermatitis Impact Questionnaire (ADIQ) Score Secondary · Baseline, Week 16

The ADIQ is a 17-item questionnaire used to assess the participant's AD-specific health-related quality of life. Each item is rated on a 5-point scale from 0 to 4, with higher numbers indicating greater burden. The questionnaire assesses AD's impact on emotions, energy, activities of daily living, and social activities. The ADIQ has a recall specification of 7 days. Assessments were recorded by the participant using an electronic diary and transferred to the clinical database.The ADIQ score is calculated by summing the score of each of the 14 questions resulting in a maximum of 56 and a minimu

GroupValue95% CI
125 mg Lebrikizumab (Q4W)-14.2± 12.74
250 mg Lebrikizumab (Q4W)-18.8± 12.03
250 mg Lebrikizumab (Q2W)-18.6± 12.63
Placebo-11.0± 13.96

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to 271 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

125 mg Lebrikizumab (Q4W)
Serious: 2/73 (3%)
Deaths: 0/73
250 mg Lebrikizumab (Q4W)
Serious: 0/80 (0%)
Deaths: 0/80
250 mg Lebrikizumab (Q2W)
Serious: 2/75 (3%)
Deaths: 0/75
Placebo
Serious: 2/52 (4%)
Deaths: 0/52

Serious adverse events (7 terms)

ReactionSystem125 mg Lebrikizumab (Q4W)250 mg Lebrikizumab (Q4W)250 mg Lebrikizumab (Q2W)Placebo
Hernial eventrationGastrointestinal disorders
Chest painGeneral disorders
Oedema peripheralGeneral disorders
Periprosthetic fractureInjury, poisoning and procedural complications
Panic attackPsychiatric disorders
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Other adverse events (190 terms — click to expand)

ReactionSystem125 mg Lebrikizumab (Q4W)250 mg Lebrikizumab (Q4W)250 mg Lebrikizumab (Q2W)Placebo
NasopharyngitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
FatigueGeneral disorders
Injection site painGeneral disorders
HeadacheNervous system disorders
DiarrhoeaGastrointestinal disorders
Injection site erythemaGeneral disorders
Back painMusculoskeletal and connective tissue disorders
AnxietyPsychiatric disorders
Dermatitis atopicSkin and subcutaneous tissue disorders
Dermatitis contactSkin and subcutaneous tissue disorders
Dry eyeEye disorders
Abdominal painGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
GastritisGastrointestinal disorders
VomitingGastrointestinal disorders
Oedema peripheralGeneral disorders
PyrexiaGeneral disorders
Bacterial vaginosisInfections and infestations
CellulitisInfections and infestations
ConjunctivitisInfections and infestations
Herpes zosterInfections and infestations
Oral herpesInfections and infestations
Pharyngitis streptococcalInfections and infestations
SinusitisInfections and infestations
Urinary tract infectionInfections and infestations
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Urine leukocyte esterase positiveInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
OsteoarthritisMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
ParaesthesiaNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
HypertensionVascular disorders
AnaemiaBlood and lymphatic system disorders
LeukocytosisBlood and lymphatic system disorders

Most-reported serious reactions: Hernial eventration, Chest pain, Oedema peripheral, Periprosthetic fracture, Panic attack, Chronic obstructive pulmonary disease, Pulmonary embolism.

Data from ClinicalTrials.gov NCT03443024 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the safety and efficacy of lebrikizumab compared with placebo in participants with moderate-to-severe atopic dermatitis.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Efficacy and Safety of Lebrikizumab, a High-Affinity Interleukin 13 Inhibitor, in Adults With Moderate to Severe Atopic Dermatitis: A Phase 2b Randomized Clinical Trial.
    Guttman-Yassky E, Blauvelt A, Eichenfield LF, Paller AS, et al · · 2020 · cited 242× · PMID 32101256 · DOI 10.1001/jamadermatol.2020.0079
  2. T cell pathology in skin inflammation.
    Sabat R, Wolk K, Loyal L, Döcke WD, et al · · 2019 · cited 134× · PMID 31028434 · DOI 10.1007/s00281-019-00742-7
  3. Neuroimmune interactions in chronic itch of atopic dermatitis.
    Yosipovitch G, Berger T, Fassett MS. · · 2020 · cited 113× · PMID 31566796 · DOI 10.1111/jdv.15973
  4. Efficacy and Safety of Lebrikizumab in Combination With Topical Corticosteroids in Adolescents and Adults With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial (ADhere).
    Simpson EL, Gooderham M, Wollenberg A, Weidinger S, et al · · 2023 · cited 92× · PMID 36630140 · DOI 10.1001/jamadermatol.2022.5534
  5. Development of therapeutic antibodies for the treatment of diseases.
    Wang Z, Wang G, Lu H, Li H, et al · · 2022 · cited 69× · PMID 36418786 · DOI 10.1186/s43556-022-00100-4
  6. Personalized medicine-concepts, technologies, and applications in inflammatory skin diseases.
    Litman T. · · 2019 · cited 51× · PMID 31124204 · DOI 10.1111/apm.12934
  7. Safety of Lebrikizumab in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis: An Integrated Analysis of Eight Clinical Trials.
    Stein Gold L, Thaçi D, Thyssen JP, Gooderham M, et al · · 2023 · cited 45× · PMID 37195407 · DOI 10.1007/s40257-023-00792-6
  8. Therapeutic Potential of Lebrikizumab in the Treatment of Atopic Dermatitis.
    Loh TY, Hsiao JL, Shi VY. · · 2020 · cited 37× · PMID 32104006 · DOI 10.2147/jaa.s211032

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing