A Study of Lebrikizumab (LY3650150) on Vaccine Response in Adults With Atopic Dermatitis (ADopt-VA)

Atopic Dermatitis Clinical Trial

Official title:

A Phase 3, 16-week, Randomized, Double-Blind, Placebo-Controlled, Parallel- Group Study to Assess the Impact of Lebrikizumab on Vaccine Responses in Adult Patients With Moderate-to-Severe Atopic Dermatitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04626297
• Other study ID #: 17946
• Secondary ID: J2T-MC-KGAK2020-
• Status: Completed
• Phase: Phase 3
• Start date: November 17, 2020
• Est. completion date: September 30, 2022

Study information

• Verified date: October 2023
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The reason for this study is to assess the impact of lebrikizumab on vaccine immune response in adult participants with moderate to severe atopic dermatitis (AD).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 254
• Est. completion date: September 30, 2022
• Est. primary completion date: August 3, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Chronic atopic dermatitis (AD) according to American Academy of Dermatology Consensus Criteria that has been present for =1 year before screening.

• 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 AD involvement at the baseline visit.

• History of inadequate response to treatment with topical medications; or determination that topical treatments are otherwise medically inadvisable.

• Have not received any tetanus-containing vaccine within approximately 5 years of baseline.

• Have never received a meningococcal conjugate vaccine or have received not more than 1 prior MCV dose at least 4 years prior to baseline, of a vaccine containing 1 or more meningococcal serogroups (serogroups A, C, W, Y).

• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

• a. Female participants of childbearing potential: must agree to remain abstinent (refrain from heterosexual intercourse) or use a highly effective contraceptive method during the treatment period and for at least 18 weeks after the last dose of study drug. Women of non-childbearing potential (non-WOCBP) may participate without any contraception requirements.

• b. Male participants are not required to use any contraception except in compliance with specific local government study requirements.

Exclusion Criteria:

• Recurring herpes simplex, herpes zoster, recurring cellulitis, chronic osteomyelitis

• Evidence of active or chronic hepatitis

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

• Presence of skin comorbidities that may interfere with study assessments.

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

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

• Have a prior history of Guillain-Barre syndrome.

• Allergic to latex.

• History of past vaccination allergy or Arthus-type hypersensitivity.

• Have an uncontrolled seizure disorder.

• Have known hypogammaglobulinemia or a screening serum immunoglobulin G (IgG) or immunoglobulin A (IgA) concentration less than the lower limit of the reporting laboratory's reference range.

• Treated with topical corticosteroids (TCS), calcineurin inhibitors, or phosphodiesterase-4 inhibitors such as crisaborole within 1 week prior to the baseline visit.

• Treated with the following prior to baseline visit:

• a. An investigational drug within 8 weeks or within 5 half-lives (if known), whichever is longer

• b. B Cell-depleting biologics, including rituximab, within 6 months

• c. Other biologics within 5 half-lives (if known) or 8 weeks, whichever is longer

• Received a Bacillus Calmette-Guerin (BCG) vaccination or treatment within 12 months of screening, or treated with a live (attenuated) vaccine within 12 weeks of the baseline visit or planned during the study.

• A contraindication to the Tdap vaccine or mean corpuscular volume (MCV).

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

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Drug:
• Lebrikizumab
Given SC
• Placebo
Given SC

Locations

Country	Name	City	State
United States	Orange County Research Institute	Anaheim	California
United States	Arlington Research Center, Inc	Arlington	Texas
United States	Oakland Dermatology	Auburn Hills	Michigan
United States	Bellaire Dermatology Associates	Bellaire	Texas
United States	Wallace Medical Group, Inc.	Beverly Hills	California
United States	Clinical Research Center of Alabama- Birmingham	Birmingham	Alabama
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Metro Boston Clinical Partners	Brighton	Massachusetts
United States	IMMUNOe International Research Centers	Centennial	Colorado
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	Asthma and Allergy Associates, PC	Colorado Springs	Colorado
United States	Florida Academic Centers Research and Education, LLC	Coral Gables	Florida
United States	Dermatology Treatment and Research Center	Dallas	Texas
United States	Modern Research Associates	Dallas	Texas
United States	Ohio Pediatric Research Association	Dayton	Ohio
United States	Austin Institute for Clinical Research	Dripping Springs	Texas
United States	Psoriasis Treatment Center of Central New Jersey	East Windsor	New Jersey
United States	First OC Dermatology	Fountain Valley	California
United States	Center For Dermatology Clinical Research, Inc.	Fremont	California
United States	Skin Laser and Surgery Specialists, a Division of Schweiger Dermatology	Hackensack	New Jersey
United States	Direct Helpers Research Center	Hialeah	Florida
United States	The Community Research of South Florida	Hialeah	Florida
United States	Burke Pharmaceutical Research	Hot Springs	Arkansas
United States	Center for Clinical Studies	Houston	Texas
United States	Suzanne Bruce and Associates, PA	Houston	Texas
United States	Axon Clinical Research	Inglewood	California
United States	Solutions Through Advanced Research	Jacksonville	Florida
United States	Clinical Partners, LLC	Johnston	Rhode Island
United States	C&R Research Services USA	Kendall	Florida
United States	Sunwise Clinical Research	Lafayette	California
United States	Avance Trials	Laguna Niguel	California
United States	Laredo Dermatology Associates P.A.	Laredo	Texas
United States	Dermatology Research Associates	Los Angeles	California
United States	Keck School of Medicine University of Southern California	Los Angeles	California
United States	LA Universal Research Center, INC	Los Angeles	California
United States	Skin Sciences, PLLC	Louisville	Kentucky
United States	Ablon Skin Institute and Research Center	Manhattan Beach	California
United States	Florida Research Center, Inc	Miami	Florida
United States	International Dermatology Research, Inc.	Miami	Florida
United States	Miami Dermatology and Laser Research	Miami	Florida
United States	New Horizon Research Center	Miami	Florida
United States	Sanchez Clinical Research Inc	Miami	Florida
United States	Wellness Clinical Research	Miami Lakes	Florida
United States	Tulane Univ School of Med	New Orleans	Louisiana
United States	JUVA Skin & Laser Center	New York	New York
United States	Dermatology Clinical Trials	Newport Beach	California
United States	Sneeze, Wheeze, & Itch Associates LLC	Normal	Illinois
United States	Arkansas Research Trials	North Little Rock	Arkansas
United States	Unity Clinical Research	Oklahoma City	Oklahoma
United States	Advanced Dermatology of the Midlands	Omaha	Nebraska
United States	Kansas City Dermatology, PA	Overland Park	Kansas
United States	Cura Clinical Research	Palmdale	California
United States	Riverchase Dermatology and Cosmetic Surgery	Pembroke Pines	Florida
United States	University of Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	The Indiana Clinical Trials Center	Plainfield	Indiana
United States	Oregon Medical Research Center	Portland	Oregon
United States	MediSearch Clinical Trials	Saint Joseph	Missouri
United States	Velocity Clinical Research - Woseth Dermatology	Salt Lake City	Utah
United States	Progressive Clinical Research	San Antonio	Texas
United States	Texas Dermatology and Laser Specialists	San Antonio	Texas
United States	MD Strategies Research Centers MDSRC	San Diego	California
United States	University Clinical Trials	San Diego	California
United States	Synergy Dermatology	San Francisco	California
United States	Care Access Research	San Jose	California
United States	San Luis Dermatology & Laser Clinic	San Luis Obispo	California
United States	Advanced Medical Research	Sandy Springs	Georgia
United States	Southern California Dermatology, Inc.	Santa Ana	California
United States	Georgia Skin & Cancer Clinic	Savannah	Georgia
United States	Kansas Medical Clinic, an Elligo Health Research, Inc.	Shawnee Mission	Kansas
United States	Jordan Valley Dermatology Center	South Jordan	Utah
United States	Premier Clinical Research	Spokane	Washington
United States	ForCare Clinical Research	Tampa	Florida
United States	Olympian Clinical Research	Tampa	Florida
United States	Tampa General Hospital	Tampa	Florida
United States	Kansas Medical Clinic	Topeka	Kansas
United States	Central States Research	Tulsa	Oklahoma
United States	Vital Prospects Clinical Research Institute, PC	Tulsa	Oklahoma
United States	Peak Research LLC	Upper Saint Clair	Pennsylvania
United States	Grekin Skin Institute	Warren	Michigan
United States	AAPRI Clinical Research Institute	Warwick	Rhode Island
United States	Center for Clinical Studies	Webster	Texas
United States	Dundee Dermatology	West Dundee	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Develop a Booster Response to Tetanus Toxoid 4 Weeks After Tdap (Tetanus-diphtheria-pertussis) Vaccine Administration	Booster response to tetanus toxoid is defined as: =4-fold increase in anti-tetanus toxoid immunoglobulin G (IgG) antibody concentration if the pre-vaccination level was >0.10 International units per milliliter (IU/mL) and =2.7 IU/mL; OR =2-fold increase in anti-tetanus toxoid IgG antibody concentration if the pre-vaccination level was >2.7 IU/mL; OR =4-fold increase in anti-tetanus toxoid IgG antibody concentration and a post-vaccination level =0.10 IU/mL if the pre-vaccination level was =0.10 IU/mL	Week 16
Primary	Percentage of Participants Who Have Positive Antibody Response to Meningococcus C Antigen 4 Weeks After Meningococcal Conjugate Vaccine (MCV) Administration	Positive antibody response to Meningococcus C antigen as measured by group C serum bactericidal antibodies is defined as: post-vaccination rabbit complement serum bactericidal assay (rSBA) titer =4 times the lower limit of quantitation (LLOQ), if the pre-vaccination rSBA titer is less than the LLOQ; OR post-vaccination rSBA titer =4 times the pre-vaccination titer, if the pre-vaccination rSBA titer is greater than or equal to the LLOQ.	Week 16
Secondary	Percentage of Participants Achieving an Investigator Global Assessment (IGA) Score of 0 or 1 and a Reduction of =2 Points From Baseline	The IGA measures the investigator's global assessment of the participants 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. Markov Chain Monte Carlo Multiple Imputation (MCMC-MI) was used to handle missing data.	Week 16
Secondary	Percentage of Participants Achieving a =75% Reduction From Baseline in Eczema Area and Severity Index Score (EASI-75)	The EASI-75 is defined as a = 75% improvement from baseline in the EASI score. EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs, by scoring the extent of disease (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 (erythema, edema/papulation, excoriation, and lichenification) each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head and neck, trunk, upper limbs, and lower limbs). Half scores are allowed. The final EASI score will be obtained by weight-averaging these 4 scores and will range from 0 to 72. A higher score represents greater disease severity. MCMC-MI was used to handle missing data.	Week 16
Secondary	Percentage of Participants Achieving =90% Reduction From Baseline in Eczema Area and Severity Index Score (EASI-90)	The EASI-90 is defined as a = 90% improvement from baseline in the EASI score. EASI assesses objective physician estimates of 2 dimensions of atopic dermatitis - disease extent and clinical signs, by scoring the extent of disease (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 (erythema, edema/papulation, excoriation, and lichenification) each on a scale of 0 to 3 (0 = none, absent; 1 = mild; 2 = moderate; 3 = severe) at 4 body sites (head and neck, trunk, upper limbs, and lower limbs). Half scores are allowed. The final EASI score will be obtained by weight-averaging these 4 scores and will range from 0 to 72. A higher score represents greater disease severity. MCMC-MI was used to handle missing data.	Week 16
Secondary	Percentage of Participants Achieving =4-Point Improvement From Baseline in Pruritus Numeric Rating Scale (NRS) Score	The Pruritus NRS is an 11-point scale used by participants to rate their worst itch severity over the past 24 hours, with 0 indicating "No itch" and 10 indicating "Worst itch imaginable." MCMC-MI was used to handle missing data.	Week 16
Secondary	Change From Baseline in Percent Body Surface Area (BSA)	The BSA assessment estimates the extent of disease or skin involvement with respect to AD and is expressed as a percentage of body surface area. It was assessed for 4 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%. BSA was calculated using the participant's palm, 1 palm = 1% with estimates of the number of palms it takes to cover the affected AD area. Maximum number of palms were 10 for head and neck (10%), 20 for upper extremities (20%), 30 for trunk, including axilla and groin (30%), and 40 for lower extremities, including buttocks (40%). Percent of BSA for a body region = total number of palms in a body region * % surface area equivalent to 1 palm. Overall percent BSA for an individual is arithmetic mean of % BSA of all 4 body regions and ranges from 0% to 100% with higher values representing greater severity of AD.	Baseline, Week 16
Secondary	Change From Baseline in Sleep-Loss Score	Sleep Loss due to interference of itch will be assessed by the participant. Participants rate their interference of itch on sleep based on a 5-point Likert scale [0 (not at all) to 4 (unable to sleep at all)]. Higher scores indicate a greater impact and worse outcome. Assessments will be recorded daily by the participant using an electronic diary, and the week 16 score was calculated by averaging the daily scores from the previous 7 days and the average score was used to compute a change from baseline. MCMC-MI was used to handle missing data.	Baseline, Week 16

External Links

•   A Study of Lebrikizumab (LY3650150) on Vaccine Response in Adults With Atopic Dermatitis (ADopt-VA)