Clinical trial NCT04146363: Evaluation of the Efficacy and Safety of Lebrikizumab (LY3650150) in Moderate to Severe Atopic Dermatitis (ADvocate1)
Official title: A Randomized, Double-blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Lebrikizumab in Patients With Moderate to Severe Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atopic Dermatitis
Keywords: Eczema
Dermatitis
Dermatitis, Atopic
Skin Diseases
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: Dermira, Inc.
First posted: 2019-10-31
Enrollment: 424
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, parallel group, placebo controlled
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With an Investigator Global Assessment (IGA) Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16
timeFrame: Baseline to Week 16
measure: Percentage of Participants Achieving Eczema Area And Severity Index (EASI-75) (≥75% Reduction in EASI Score) From Baseline to Week 16
timeFrame: Baseline to Week 16
Secondary outcomes:
measure: Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 2
timeFrame: Baseline to Week 2
measure: Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 4
timeFrame: Baseline to Week 4
measure: Percentage of Participants With an IGA Score of 0 or 1 and a Reduction ≥2 Points From Baseline to Week 16 in Adults
timeFrame: Baseline to Week 16
measure: Percentage of Participants Achieving EASI-90 (≥90% Reduction in EASI Score) From Baseline to Week 16
timeFrame: Baseline to Week 16
measure: Percent Change in Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16
timeFrame: Baseline, Week 16
measure: 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
timeFrame: Baseline to Week 16
measure: 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
timeFrame: Baseline to Week 16
measure: Percent Change in EASI Score From Baseline to Week 16
timeFrame: Baseline, Week 16
measure: Change From Baseline in Percent Body Surface Area (BSA) at Week 16
timeFrame: Baseline, Week 16
measure: Percentage of Participants Achieving EASI-90 From Baseline to Week 4
timeFrame: Baseline to Week 4
measure: Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16
timeFrame: Baseline, Week 16
measure: Percentage of Participants Achieving ≥4 Point Improvement in DLQI From Baseline to Week 16
timeFrame: Baseline to Week 16
measure: Percentage of Participants With a DLQI Total Score of ≥4-point at Baseline Achieving ≥4-point Improvement in DLQI From Baseline to Week 16
timeFrame: Baseline to Week 16
measure: Percent Change in Sleep-loss Score From Baseline to Week 16
timeFrame: Baseline, Week 16
measure: Change From Baseline in Sleep-loss Score at Week 16
timeFrame: Baseline, Week 16
measure: Percentage of Participants With a Sleep-loss Score ≥2 Points at Baseline Who Achieve a ≥2 Points Reduction From Baseline at Week 16
timeFrame: Baseline to Week 16
measure: Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1
timeFrame: Baseline to Week 1
measure: Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2
timeFrame: Baseline to Week 2
measure: Percentage of Participants With a Pruritus NRS Score of ≥4 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4
timeFrame: Baseline to Week 4
measure: Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 1
timeFrame: Baseline to Week 1
measure: Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 2
timeFrame: Baseline to Week 2
measure: Percentage of Participants With a Pruritus NRS Score of ≥5 Points at Baseline Who Achieve a ≥4-point Reduction From Baseline to Week 4
timeFrame: Baseline to Week 4
measure: Percent Change in SCORing Atopic Dermatitis (SCORAD) From Baseline to Week 16
timeFrame: Baseline, Week 16
measure: Pharmacokinetics (PK): Average Serum Concentration of Lebrikizumab at Week 52
timeFrame: Predose: Baseline, Week 4, Week 16, Week 32, Week 52
measure: 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)
timeFrame: Baseline to Week 52
measure: 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
timeFrame: Baseline to Week 52
measure: 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
timeFrame: Baseline to Week 52
measure: 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
timeFrame: Baseline to Week 52
measure: Percent Change in SCORAD (Having Achieved EASI-75 at Week 16) From Baseline at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) at Week 16 - Health State Index
timeFrame: Baseline, Week 16
measure: Change From Baseline in EQ-5D-5L at Week 16 - Visual Analog Scale (VAS)
timeFrame: Baseline, Week 16
measure: Change From Baseline in Patient Oriented Eczema Measure (POEM) at Week 16
timeFrame: Baseline, Week 16
measure: Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety at Week 16 - Adolescents
timeFrame: Baseline, Week 16
measure: Change From Baseline in PROMIS Depression at Week 16 - Adolescents
timeFrame: Baseline, Week 16
measure: Change From Baseline in PROMIS Anxiety at Week 16 - Adults
timeFrame: Baseline, Week 16
measure: Change From Baseline in PROMIS Depression at Week 16 - Adults
timeFrame: Baseline, Week 16
measure: Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score at Week 16 in Participants Who Have Self-Reported Comorbid Asthma
timeFrame: Baseline, Week 16
measure: Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) at Week 16 - Adolescents
timeFrame: Baseline, Week 16
Other outcomes:
Locations:
city: Fort Smith
country: United States
facility: Johnson Dermatology
state: Arkansas
city: Beverly Hills
country: United States
facility: Wallace Medical Group, Inc.
state: California
city: Encinitas
country: United States
facility: California Dermatology & Clinical Research Institute
state: California
city: Fountain Valley
country: United States
facility: Belle Aimee Skincare Clinic
state: California
city: Los Angeles
country: United States
facility: Dermatology Research Associates
state: California
city: San Diego
country: United States
facility: ACRC Studies
state: California
city: Cromwell
country: United States
facility: Central Connecticut Dermatology
state: Connecticut
city: Clearwater
country: United States
facility: St. Francis Medical Institute
state: Florida
city: Miami
country: United States
facility: Community Research Foundation Inc
state: Florida
city: Tampa
country: United States
facility: ForCare Clinical Research
state: Florida
city: Columbus
country: United States
facility: IACT Health - VHC
state: Georgia
city: Plainfield
country: United States
facility: The Indiana Clinical Trials Center
state: Indiana
city: Louisville
country: United States
facility: Skin Sciences, PLLC
state: Kentucky
city: Quincy
country: United States
facility: Beacon Clinical Research, LLC
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Saint Joseph
country: United States
facility: St Joseph Dermatology and Vein Clinic
state: Michigan
city: Saint Joseph
country: United States
facility: MediSearch Clinical Trials
state: Missouri
city: Las Vegas
country: United States
facility: JDR Dermatology Research
state: Nevada
city: Portsmouth
country: United States
facility: ALLCUTIS Research
state: New Hampshire
city: New York
country: United States
facility: Icahn Sch of Med at Mt. Sinai
state: New York
city: New York
country: United States
facility: Sadick Research Group
state: New York
city: Raleigh
country: United States
facility: Wake Research Associates
state: North Carolina
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Tulsa
country: United States
facility: Vital Prospects Clinical Research Institute, P.C.
state: Oklahoma
city: Medford
country: United States
facility: Clinical Research Institute
state: Oregon
city: Portland
country: United States
facility: Oregon Medical Research Center
state: Oregon
city: Johnston
country: United States
facility: Clinical Partners, LLC
state: Rhode Island
city: Bellaire
country: United States
facility: Bellaire Dermatology
state: Texas
city: San Antonio
country: United States
facility: Progressive Clinical Research
state: Texas
city: Spokane
country: United States
facility: Premier Clinical Research
state: Washington
city: Kogarah
country: Australia
facility: The St. George Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Holdsworth House Medical Practice
state: New South Wales
city: Westmead
country: Australia
facility: Skin & Cancer Foundation Australia
state: New South Wales
city: Benowa
country: Australia
facility: The Skin Centre
state: Queensland
city: Woolloongabba
country: Australia
facility: Veracity Clinical Research Pty Ltd
state: Queensland
city: Box Hill
country: Australia
facility: Eastern Clinical Research Unit
state: Victoria
city: Camberwell
country: Australia
facility: Emeritus Research
state: Victoria
city: Carlton
country: Australia
facility: Skin Health Institute Inc.
state: Victoria
city: East Melbourne
country: Australia
facility: Sinclair Dermatology
state: Victoria
city: Fremantle
country: Australia
facility: Fremantle Dermatology
state: Western Australia
city: Victoria Park
country: Australia
facility: Burswood Dermatology
state: Western Australia
city: Red Deer
country: Canada
facility: CARe Clinic
state: Alberta
city: Ajax
country: Canada
facility: CCA Medical Research
state: Ontario
city: Cobourg
country: Canada
facility: Skin Health
state: Ontario
city: Ottawa
country: Canada
facility: Dermatology and Dermatologic Surgery
state: Ontario
city: Richmond Hill
country: Canada
facility: The Centre for Dermatology
state: Ontario
city: Tartu
country: Estonia
facility: Kliiniliste uuringute Keskus OU
city: Paris
country: France
facility: Hopital Saint-Louis
state: Cedex 10
city: Bordeaux Cedex
country: France
facility: CHU de Bordeaux Hopital Saint Andre
city: Dijon Cedex
country: France
facility: CHU DIJON - Hopital le Bocage
city: Martigues
country: France
facility: Cabinet Médical
city: Toulouse cedex 9
country: France
facility: Hopital Larrey
city: Ansan-si
country: Korea, Republic of
facility: Korea University Ansan Hospital
state: Gyeonggi-do
city: Pusan
country: Korea, Republic of
facility: Pusan National University Hospital
state: Korea
city: Seoul
country: Korea, Republic of
facility: Hanyang University Medical Center
state: Korea
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
state: Korea
city: Suwon-si
country: Korea, Republic of
facility: Ajou University Hospital
state: Kyung Gi-Do, Korea
city: Seoul
country: Korea, Republic of
facility: Soon Chun Hyang University Seoul Hospital
state: Yongsan-gu
city: Incheon
country: Korea, Republic of
facility: Incheon St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
city: Seoul
country: Korea, Republic of
facility: Chungang University Hospital
city: Seoul
country: Korea, Republic of
facility: Hallym University Kangnam Sacred Heart Hospital
city: Riga
country: Latvia
facility: Clinic of Dermatology and STD
city: Riga
country: Latvia
facility: Health Center 4, Affiliate Diagnostic Center
city: Riga
country: Latvia
facility: Health and Aesthetics LTD
city: Riga
country: Latvia
facility: Latvian Dermatology Institute
city: Talsi
country: Latvia
facility: Smite Aija - Practice in Dermatology Venereology
city: Kaunas
country: Lithuania
facility: JSC "CD8 Alergology Clinic"
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kauno klinikos
city: Vilnius
country: Lithuania
facility: Jsc Renmeda
city: Vilnius
country: Lithuania
facility: JSC "Center for Diagnosis and Treatment of Allergic Diseases"
city: Vilnius
country: Lithuania
facility: Children's Hospital, Affiliate of Vilnius University Hospital Santaros klinikos
city: Vilnius
country: Lithuania
facility: Inlita (Santaros CTC)
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santaros klinikos
city: Tarnow
country: Poland
facility: Alergo-Med Specjalistyczna Przychodnia Lekarska Sp Z O.O.
state: Malopolska
city: Krakow
country: Poland
facility: Diamond Clinic
state: Malopolskie
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny MSWiA
state: Mazowieckie
city: Katowice
country: Poland
facility: Centrum Medyczne Angelius Provita
state: Slaskie
city: Szczecin
country: Poland
facility: Twoja Przychodnia - Szczecinskie Centrum Medyczne
state: West Pomeranian
city: Iwonicz Zdroj
country: Poland
facility: Zespol Naukowo - Leczniczy "Iwolang" Sp. z o.o.
state: Wojewodztwo Podkarpackie
city: Katowice
country: Poland
facility: GynCentrum Sp z o.o.
city: Krakow
country: Poland
facility: Specjalistyczny Osrodek Alergologiczno-Internistyczny ALL-ME
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 1
city: Poznan
country: Poland
facility: Centrum Alergologii Teresa Hofman
city: Warszawa
country: Poland
facility: Clinical Research Group Sp. z o.o.
city: Wroclaw
country: Poland
facility: CityClinic Przychodnia Lekarsko-Psychologiczna
city: SANT BOI DE Llobrega
country: Spain
facility: Sant Joan de Deu Serveis En Salut Mental
state: Barcelona
city: Bilbao
country: Spain
facility: Hospital De Basurto
state: Vizcaya
city: Alicante
country: Spain
facility: Hospital General Universitario Alicante
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: Hospital Infanta Leonor
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: