Tralokinumab Monotherapy for Moderate to Severe Atopic Dermatitis - ECZTRA 2 (ECZema TRAlokinumab Trial no. 2)

Atopic Dermatitis Clinical Trial

— ECZTRA 2  

Official title:

A Randomised, Double-blind, Placebo-controlled, Phase 3 Trial to Evaluate the Efficacy and Safety of Tralokinumab Monotherapy in Subjects With Moderate to Severe Atopic Dermatitis Who Are Candidates for Systemic Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03160885
• Other study ID #: LP0162-1326
• Secondary ID: 2016-004201-13
• Status: Completed
• Phase: Phase 3
• Start date: June 12, 2017
• Est. completion date: August 14, 2019

Study information

• Verified date: February 2023
• Source: LEO Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary objective:

To evaluate the efficacy of tralokinumab compared with placebo in treating moderate to severe atopic dermatitis (AD).

Secondary objectives:

To evaluate the efficacy of tralokinumab on severity and extent of AD, itch, and health related quality of life compared with placebo.

Maintenance objective:

To evaluate maintenance of effect with continued tralokinumab dosing up to 52 weeks compared to placebo for subjects achieving clinical response at Week 16.

Description:

Subjects found eligible following the screening period were randomized 3:1 to initial treatment with tralokinumab 300 mg every 2 weeks (Q2W) or placebo. Randomization was stratified by region (Asia, Australia, Europe, and North America) and disease severity (Investigator's Global Assessment [IGA] 3 or 4).

Subjects achieving a clinical response at Week 16 (defined as IGA of 0 or 1 on a 5-point scale ranging from 0 [clear] to 4 [severe], or at least 75% reduction in Eczema Area and Severity Index [EASI] score from baseline [EASI75]) continued into maintenance treatment that continued until Week 52.

Subjects randomized to tralokinumab in the initial treatment period and who achieved a clinical response at Week 16 (defined by IGA 0 or 1, or EASI75) were re-randomized 2:2:1 to one of the following Q2W maintenance regimens stratified by region (Asia, Australia, Europe, and North America) and IGA response at Week 16 (IGA 0/1 or IGA >1):

• Tralokinumab 300 mg Q2W.

• Tralokinumab 300 mg Q4W (alternating dose administrations tralokinumab 300 mg and placebo).

• Placebo.

Subjects randomized to placebo in the initial treatment period who achieved a clinical response at Week 16 (defined by IGA 0 or 1, or EASI75) continued to receive placebo Q2W in the maintenance treatment period.

Subjects not achieving a clinical response at Week 16 as well as those who met the criteria listed below during maintenance treatment were transferred to open-label tralokinumab 300 mg Q2W treatment with optional use of topical corticosteroid (TCS) up to Week 52.

Transfer to open-label treatment during maintenance:

Subjects with IGA=0 at Week 16: IGA of at least 2 and not achieved EASI75 over at least a 4-week period (i.e. over 3 consecutive visits).

Subjects with IGA=1 at Week 16: IGA of at least 3 and not achieved EASI75 over at least a 4-week period (i.e. over 3 consecutive visits).

Subjects with IGA >1 at Week 16: not achieved EASI75 over at least a 4-week period (i.e. over 3 consecutive visits).

Subjects transferring to open-label treatment had the option to self-administer tralokinumab in their home after adequate training (at 3 dosing visits in the open-label period after additional consent has been obtained) by site staff at the investigator's discretion.

After completion of the maintenance treatment period (or open-label treatment), all subjects, except for those who entered the open-label long-term extension trial, continued in a 14-week off-treatment follow-up period for the assessment of safety and anti-drug antibody (ADA).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 794
• Est. completion date: August 14, 2019
• Est. primary completion date: September 4, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Written informed consent and any locally required authorisation obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.

2. Age 18 and above.

3. Diagnosis of AD as defined by the Hanifin and Rajka (1980) criteria for AD (33; Appendix 5).

4. Diagnosis of AD for =1 year.

5. Subjects who have a recent history (within 1 year before the screening visit) of inadequate response to treatment with topical medications or for whom topical treatments are otherwise medically inadvisable (e.g., due to important side effects or safety risks).

• Inadequate response is defined as failure to achieve and maintain remission or a low disease activity state (comparable to IGA 0=clear to 2=mild) despite treatment with a daily regimen of TCS of medium to higher potency (±TCI as appropriate), applied for at least 28 days or for the maximum duration recommended by the product prescribing information (e.g., 14 days for super potent TCS), whichever is shorter.

• Subjects with documented systemic treatment for AD in the past year are also considered as inadequate responders to topical treatments and are potentially eligible for treatment with tralokinumab after appropriate washout.

• Important side effects or safety risks are those that outweigh the potential treatment benefits and include intolerance to treatment, hypersensitivity reactions, significant skin atrophy, and systemic effects, as assessed by the investigator or by the subject's treating physician.

6. AD involvement of =10% body surface area at screening and baseline (visit 3).

7. An EASI score of =12 at screening and 16 at baseline.

8. An IGA score of =3 at screening and at baseline.

9. A Worst Daily Pruritus numeric rating scale (NRS) average score of =4 during the week prior to baseline.

• Worst Daily Pruritus NRS at baseline will be calculated from daily assessments of worst itch severity (Worst Daily Pruritus NRS) during the 7 days immediately preceding randomisation (Day 6 to 0). A minimum of 4 Worst Daily Pruritus NRS scores out of the 7 days is required to calculate the baseline average score. For subjects who do not have at least 4 scores reported during the 7 days immediately preceding the planned randomisation date, randomisation should be postponed until this requirement is met, but without exceeding the 6 weeks maximum duration for screening.

10. Subjects must have applied a stable dose of emollient twice daily (or more, as needed) for at least 14 days before randomisation (refer to exclusion criterion no. 8 for limitations regarding emollients).

11. Women of childbearing potential must use a highly effective* form of birth control (confirmed by the investigator) throughout the trial and at least for 16 weeks (5 half lives) after last administration of IMP.

• A highly effective method of birth control is defined as one which results in a low failure rate (less than 1% per year) such as bilateral tubal occlusion, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), sexual abstinence (when this is in line with the preferred and usual life style of the subject), vasectomised partner (given that the subject is monogamous). The subjects must have used the contraceptive method continuously for at least 1 month prior to the pregnancy test at baseline. A female is defined as not being of child-bearing potential if she is postmenopausal (at least 12 months with no menses without an alternative medical cause prior to screening), or surgically sterile (hysterectomy, bilateral salpingectomy or bilateral oophorectomy).

Exclusion Criteria:

1. Concurrent enrolment in another clinical trial where the subject is receiving an IMP.

2. Previous randomisation in tralokinumab trials.

3. Active dermatologic conditions that may confound the diagnosis of AD or would interfere with assessment of treatment, such as scabies, cutaneous lymphoma, or psoriasis.

4. Known active allergic or irritant contact dermatitis that is likely to interfere with the assessment of severity of AD.

5. Use of tanning beds or phototherapy (narrow band ultraviolet B [NBUVB], ultraviolet B [UVB], ultraviolet A1 [UVA1], psoralen + ultraviolet A [PUVA]), within 6 weeks prior to randomisation.

6. Treatment with the following medications within 4 weeks prior to randomisation:

• Systemic immunosuppressive/immunomodulating drugs (e.g. methotrexate, cyclosporine, azathioprine, mycophenolate mofetil, Janus kinase inhibitors etc.).

• Systemic corticosteroid use (excludes topical, inhaled, or intranasal delivery).

• Three or more bleach baths during any week within the 4 weeks.

7. Treatment with the following medications within 2 weeks prior to randomisation

• TCS.

• TCI.

• Topical PDE 4 inhibitor.

8. Initiation of treatment of AD with prescription emollients or emollients containing additives such as ceramide, hyaluronic acid, urea, or filaggrin degradation products during the screening period (subjects may continue using stable doses of such emollients if initiated before the screening visit).

9. Receipt of live attenuated vaccines 30 days prior to the date of randomisation and during the trial including the safety follow-up period.

• Receipt of inactive/killed vaccinations (e.g. inactive influenza) are allowed, provided they are not administered within 5 days before/after any study visit.

10. Receipt of any marketed (i.e. immunoglobulin, anti-IgE) or investigational biologic agent, including dupilumab:

• Any cell-depleting agents including but not limited to rituximab: within 6 months prior to randomisation, or until lymphocyte count returns to normal, whichever is longer.

• Other biologics: within 3 months or 5 half-lives, whichever is longer, prior to randomisation.

11. Receipt of any investigational non-biologic agent within 5 half-lives prior to randomisation.

12. Receipt of blood products within 4 weeks prior to screening.

13. Major surgery within 8 weeks prior to screening, or planned in-patient surgery or hospitalisation during the trial period.

14. Known or suspected allergy or reaction to any component of the IMP formulation.

15. History of any active skin infection within 1 week prior to randomisation.

16. History of a clinically significant infection within 4 weeks prior to randomisation which, in the opinion of the investigator or sponsor's medical expert, may compromise the safety of the subject in the trial, interfere with evaluation of the IMP, or reduce the subject's ability to participate in the trial. Clinically significant infections are defined as:

• a systemic infection.

• a serious skin infection requiring parenteral (intravenous or intramuscular) antibiotics, antiviral, or antifungal medication.

17. A helminth parasitic infection within 6 months prior to the date informed consent is obtained that has not been treated with, or has failed to respond to, standard of care therapy.

18. History of anaphylaxis following any biologic therapy.

19. History of immune complex disease.

20. History of cancer:

• Subjects who have had basal cell carcinoma, localised squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible provided that the subject is in remission and curative therapy was completed at least 12 months prior to the date informed consent was obtained.

• Subjects who have had other malignancies are eligible provided that the subject is in remission and curative therapy was completed at least 5 years prior to the date informed consent was obtained.

21. Tuberculosis requiring treatment within the 12 months prior to screening. Evaluation will be according to local guidelines as per local standard of care.

22. History of any known primary immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test at screening, or the subject taking antiretroviral medications as determined by medical history and/or subject's verbal report.

23. History of chronic alcohol or drug abuse within 12 months prior to screening, or any condition associated with poor compliance as judged by the investigator.

24. History of attempted suicide or is at significant risk of suicide (either in the opinion of the investigator or defined as a "yes" to suicidal ideation questions no. 4 or 5 or answering "yes" to suicidal behaviour on the Columbia-Suicide Severity Rating Scale [C-SSRS] Screening version).

25. Any disorder, including but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, immunological, psychiatric, or major physical impairment that is not stable, in the opinion of the investigator, and could:

• Affect the safety of the subject throughout the trial.

• Influence the findings of the trial or their interpretations.

• Impede the subject's ability to complete the entire duration of trial.

26. Any clinically significant abnormal findings in physical examination, vital signs, electrocardiogram (ECG), haematology, clinical chemistry, or urinalysis during the screening period, which in the opinion of the investigator, may put the subject at risk because of his/her participation in the trial, or may influence the results of the trial, or the subject's ability to complete entire duration of the trial.

27. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level =2.0 times the ULN (upper limit of normal) at screening.

28. Positive hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B core antibody (HBcAb) or hepatitis C virus antibody (anti-HCV) serology at screening. Subjects with positive HBsAb may be randomised provided they are hepatitis B vaccinated and have negative HBsAg and HBcAb.

29. Subjects who are not willing to abstain from donating blood and/or plasma from the time of informed consent and for 16 weeks (5 half-lives) after last dose of IMP.

30. Subjects who are legally institutionalised.

31. Pregnant, breastfeeding, or lactating women.

32. Employees of the trial site or any other individuals directly involved with the planning or conduct of the trial, or immediate family members of such individuals.

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Drug:
• Tralokinumab
Tralokinumab is a human recombinant monoclonal antibody of the IgG4 subclass that specifically binds to human IL-13 and blocks interaction with the IL-13 receptors. It is presented as a liquid formulation for subcutaneous (SC) administration
• Placebo
Placebo contains the same excipients, in the same concentration only lacking tralokinumab

Locations

Country	Name	City	State
Australia	Skin & Cancer Foundation Inc.	Carlton	Victoria
Australia	Skin & Cancer Foundation Australia	Darlinghurst	New South Wales
Australia	Sinclair Dermatology	East Melbourne	Victoria
Australia	St. George Dermatology and Skin Cancer Center	Kogarah	New South Wales
Australia	Woden Dermatology Pty Ltd.	Phillip	Australian Capital Territory
Australia	Burswood Dermatology	Victoria Park	Western Australia
Australia	Veracity Clinical Research	Woolloongabba	Queensland
Canada	Kingsway Clinical Research	Etobicoke	Ontario
Canada	Brunswick Dermatology Centre	Fredericton	New Brunswick
Canada	Eastern Canada Cutaneous Research	Halifax	Nova Scotia
Canada	Guenther Derm Research Centre	London	Ontario
Canada	Lynderm Research Inc.	Markham	Ontario
Canada	DermEdge Research	Mississauga	Ontario
Canada	Dr. David Gratton Dermatologue	Montréal	Quebec
Canada	Dermatology & Cosmetic Surgery	North Bay	Ontario
Canada	Derm Clinic of Dr. Robern	Ottawa	Ontario
Canada	Skin Centre for Dermatology	Peterborough	Ontario
Canada	CRDQ	Québec	Quebec
Canada	Dermatology & Cosmetic Surgery	Richmond Hill	Ontario
Canada	Nexus Clinical Research	St. John's	Newfoundland and Labrador
Canada	Dr. Chih-ho Hong Medical	Surrey	British Columbia
Canada	Enverus Medical Research	Surrey	British Columbia
Canada	Pacific Derm	Vancouver	British Columbia
Canada	K. Papp	Waterloo	Ontario
Canada	XLR8 Medical Research	Windsor	Ontario
Canada	Winnipeg Clinic	Winnipeg	Manitoba
Canada	Wiseman Dermatology Research	Winnipeg	Manitoba
Denmark	Aarhus University Hospital	Aarhus
Denmark	Bispebjerg Hospital	Hellerup
Denmark	Gentofte Hospital	Hellerup
Italy	Spedali Civili Brescia	Brescia
Italy	Policlinico-Vittorio Emanuele	Catania
Italy	Opedale San Salvatore	L'Aquila
Italy	AOU Pisa	Pisa
Italy	IRCCS San Gallicano	Rom
Italy	Policlinico "Agostino Gemelli"	Rom
Italy	Istituto Clinico Humanitas	Rozzano
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Chungnam National Univeristy	Daejeon
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Korea University Ansan Hospital	Gyeonggi-do
Korea, Republic of	Soon Chun Hyang University Hospital	Gyeonggi-do
Korea, Republic of	Inha University Hospital	Incheon
Korea, Republic of	St. Mary's Hospital	Incheon
Korea, Republic of	Chung-Ang University Hospital	Seoul
Korea, Republic of	Hallym University Kangnam Sacr	Seoul
Korea, Republic of	Konkuk University Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Yonsei University Health Syste	Seoul
Poland	Centrum Medyczne Gdynia	Gdynia
Poland	Synexus Polska Gdyni	Gdynia
Poland	Synexus Polska Katowicach	Katowice
Poland	Centrum Medyczne PRATIA	Kraków
Poland	Krakowskie Centrum Medyczne	Kraków
Poland	"DERMED" Centrum Medyczne Sp.	Lódz
Poland	Dermoklinika Centrum Medyczne	Lódz
Poland	Synexus Polska Poznaniu	Poznan
Poland	Klinika Dermatologii	Rzeszów
Russian Federation	Chelyabinsk Dermat. Dispensary	Chelyabinsk
Russian Federation	Federal State Budgetary Institution State Sci. Ctr.	Moscow
Russian Federation	French clinic of skin diseases	Saint Petersburg
Russian Federation	Military Medical Academy	Saint Petersburg
United Kingdom	West Suffolk Hospital	Bury St Edmunds
United Kingdom	Russells Hall Hospital	Dudley	West Midlands
United Kingdom	Ninewells Hospital	Dundee	Angus
United Kingdom	Harrogate District Hospital	Harrogate	North Yorkshire
United Kingdom	Chapel Allerton Hospital	Leeds	West Yorkshire
United Kingdom	Whipps Cross University Hospital	Leytonstone	London
United Kingdom	Guy's Hospital	London
United Kingdom	The Whittington Hospital NHS	London
United Kingdom	Royal Victoria Infirmary	Newcastle upon Tyne	Tyne And Wear
United Kingdom	East Surrey Hospital	Redhill	Surrey
United Kingdom	Salford Royal Hospital	Salford	Greater Manchester
United Kingdom	Royal Hallamshire Hospital	Sheffield	South Yorkshire
United Kingdom	Walsall Healthcare NHS Trust	Walsall	West Midlands
United States	Bellaire Dermatology Associates	Bellaire	Texas
United States	Clinical Research Center of the Carolinas	Charleston	South Carolina
United States	Northwestern University	Chicago	Illinois
United States	RUSH University	Chicago	Illinois
United States	University of Cincinnati Health Physicians Office	Cincinnati	Ohio
United States	Olympian Clinical Research	Clearwater	Florida
United States	Corning Center for Clinical Research	Corning	New York
United States	Modern Research Associates, PLLC	Dallas	Texas
United States	HFMC New Center One	Detroit	Michigan
United States	Psoriasis Treatment Center of Central New Jersey	East Windsor	New Jersey
United States	California dermatology	Encinitas	California
United States	Wright State Physicians	Fairborn	Ohio
United States	Advanced SkinCare Surgery & Med Center	Fullerton	California
United States	Rivergate Dermatology Clinical Research Center	Goodlettsville	Tennessee
United States	Clinical Studies Group	Henderson	Nevada
United States	Burke Pharmaceutical Research	Hot Springs	Arkansas
United States	Dawes-Fretzin Clinical Research Group, LLC	Indianapolis	Indiana
United States	USC Department of Dermatology	Los Angeles	California
United States	Marietta Dermatology Clinical Research, Inc.	Marietta	Georgia
United States	Spotlight Research Center, LLC	Miami	Florida
United States	Thiele Dermatology Specialists, Inc	Murrieta	California
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Sadick Dermatology	New York	New York
United States	MedaPhase, Inc.	Newnan	Georgia
United States	Island Dermatology	Newport Beach	California
United States	Private Practice - Dr. Tory P. Sullivan	North Miami Beach	Florida
United States	Kansas City Dermatology, PA	Overland Park	Kansas
United States	Austin Institute for Clinical Research, Inc.	Pflugerville	Texas
United States	Paddington Testing Company, Inc.	Philadelphia	Pennsylvania
United States	Oregon Dermatology and Research Center	Portland	Oregon
United States	Beacon Clinical Research	Quincy	Massachusetts
United States	Progressive Clinical Research	San Antonio	Texas
United States	Therapeutics Clinical Research	San Diego	California
United States	San Luis Dermatology and Laser Clinic	San Luis Obispo	California
United States	Southern California Dermatology, Inc.	Santa Ana	California
United States	The Grekin Skin Institute	Warren	Michigan
United States	Aventiv Research Inc.	Westerville	Ohio
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Yardley Dermatology Associates	Yardley	Pennsylvania
United States	Respiratory Medicine Research Institute of Michigan, PLC	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
LEO Pharma

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Denmark,  Italy,  Korea, Republic of,  Poland,  Russian Federation,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16.	The IGA is an instrument used in clinical trials to rate the severity of the subject's global AD and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).	At Week 16
Primary	Subjects Achieving at Least 75% Reduction in Eczema Area and Severity Index [EASI].	The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition.	At Week 16
Secondary	Reduction of Worst Daily Pruritus Numeric Rating Scale (Weekly Average) of at Least 4 From Baseline to Week 16.	Subjects will assess their worst itch severity over the past 24 hours using an 11 point NRS ('Worst Daily Pruritus NRS') with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'.	Week 0 to Week 16
Secondary	Change in Scoring Atopic Dermatitis (SCORAD) From Baseline to Week 16.	The SCORAD is a validated tool to evaluate the extent and severity of AD lesions, along with subjective symptoms. The maximum total score is 103, with higher values indicating more severe disease.	Week 0 to Week 16
Secondary	Change in Dermatology Life Quality Index (DLQI) Score From Baseline to Week 16.	The DLQI is a validated questionnaire with content specific to those with dermatology conditions. It consists of 10 items addressing the subject's perception of the impact of their skin disease on different aspects of their quality of life (QoL) over the last week such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4 point Likert scale (0 = not at all/not relevant; 1 = a little; 2 = a lot; 3 = very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor QoL.	Week 0 to Week 16
Secondary	Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 52 Among Subjects With IGA of 0/1 at Week 16	The IGA is an instrument used in clinical trials to rate the severity of the subject's global AD and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).	At Week 52
Secondary	Subjects With at Least 75% Reduction in Eczema Area and Severity Index [EASI] at Week 52 Among Subjects With EASI75 at Week 16	The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition.	At Week 52
Secondary	Safety and Tolerability: Adverse Event (AE) /Serious Adverse Event (SAE) Frequency	Overall summary of AEs and SAEs during the Initial treatment period is presented. For list of AEs and SAEs by MedDRA system organ class (SOC) and preferred term (PT) during the entire trial period (including safety follow-up), see Adverse Events Overview section.	Week 0 to Week 16
Secondary	Frequency of Anti-drug Antibodies	Anti-tralokinumab antibody levels were analysed using a validated bioanalytical method	Week 0 to Week 16
Secondary	Subjects Achieving at Least 50% Reduction in Eczema Area and Severity Index [EASI] at Week 16	The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition.	At Week 16
Secondary	Subjects Achieving at Least 90% Reduction in Eczema Area and Severity Index [EASI] at Week 16.	The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition.	At Week 16
Secondary	Change From Baseline to Week 16 in Eczema Area and Severity Index [EASI] Score	The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition.	At Week 16
Secondary	Subjects Achieving at Least 75% Reduction in Scoring Atopic Dermatitis (SCORAD) at Week 16.	The SCORAD is a validated tool to evaluate the extent and severity of AD lesions, along with subjective symptoms. The maximum total score is 103, with higher values indicating more severe disease.	At Week 16
Secondary	Subjects Achieving at Least 50% Reduction in Scoring Atopic Dermatitis (SCORAD) at Week 16.	The SCORAD is a validated tool to evaluate the extent and severity of AD lesions, along with subjective symptoms. The maximum total score is 103, with higher values indicating more severe disease.	At Week 16
Secondary	Change From Baseline to Week 16 in Worst Daily Pruritus NRS (Weekly Average).	Subjects will assess their worst itch severity over the past 24 hours using an 11 point NRS ('Worst Daily Pruritus NRS') with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'	Baseline to Week 16
Secondary	Reduction of Worst Daily Pruritus NRS (Weekly Average) =3 From Baseline to Week 16.	Subjects will assess their worst itch severity over the past 24 hours using an 11 point NRS ('Worst Daily Pruritus NRS') with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'.	Baseline to Week 16
Secondary	Reduction From Baseline to Week 16 of Dermatology Life Quality Index (DLQI) of =4 Points Among Subjects With Baseline DLQI =4.	The DLQI is a validated questionnaire with content specific to those with dermatology conditions. It consists of 10 items addressing the subject's perception of the impact of their skin disease on different aspects of their QoL over the last week such as dermatology related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4 point Likert scale (0 = not at all/not relevant; 1 = a little; 2 = a lot; 3 = very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor QoL.	Baseline to Week 16