Psoriasis Clinical Trial

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

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.

View Full Description

Full 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).

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Written informed consent and any locally required authorisation obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
Age 18 and above.
Diagnosis of AD as defined by the Hanifin and Rajka (1980) criteria for AD (33; Appendix 5).
Diagnosis of AD for ≥1 year.

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.
AD involvement of ≥10% body surface area at screening and baseline (visit 3).
An EASI score of ≥12 at screening and 16 at baseline.
An IGA score of ≥3 at screening and at baseline.

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.

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).

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:

Concurrent enrolment in another clinical trial where the subject is receiving an IMP.
Previous randomisation in tralokinumab trials.
Active dermatologic conditions that may confound the diagnosis of AD or would interfere with assessment of treatment, such as scabies, cutaneous lymphoma, or psoriasis.
Known active allergic or irritant contact dermatitis that is likely to interfere with the assessment of severity of AD.
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.

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.

Treatment with the following medications within 2 weeks prior to randomisation

TCS.
TCI.
Topical PDE 4 inhibitor.
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).

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.

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.
Receipt of any investigational non-biologic agent within 5 half-lives prior to randomisation.
Receipt of blood products within 4 weeks prior to screening.
Major surgery within 8 weeks prior to screening, or planned in-patient surgery or hospitalisation during the trial period.
Known or suspected allergy or reaction to any component of the IMP formulation.
History of any active skin infection within 1 week prior to randomisation.

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.
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.
History of anaphylaxis following any biologic therapy.
History of immune complex disease.

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

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.
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.
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.0 times the ULN (upper limit of normal) at screening.
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.
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.
Subjects who are legally institutionalised.
Pregnant, breastfeeding, or lactating women.
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.

Study is for people with:

Psoriasis

Phase:

Phase 3

Estimated Enrollment:

794

Study ID:

NCT03160885

Recruitment Status:

Completed

Sponsor:

LEO Pharma

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There are 112 Locations for this study

See Locations Near You

Burke Pharmaceutical Research
Hot Springs Arkansas, 71913, United States
California dermatology
Encinitas California, 92024, United States
Advanced SkinCare Surgery & Med Center
Fullerton California, 92835, United States
USC Department of Dermatology
Los Angeles California, 90033, United States
Thiele Dermatology Specialists, Inc
Murrieta California, 92562, United States
Island Dermatology
Newport Beach California, 92660, United States
Therapeutics Clinical Research
San Diego California, 92123, United States
San Luis Dermatology and Laser Clinic
San Luis Obispo California, 93405, United States
Southern California Dermatology, Inc.
Santa Ana California, 92701, United States
Olympian Clinical Research
Clearwater Florida, 33756, United States
Spotlight Research Center, LLC
Miami Florida, 33176, United States
Private Practice - Dr. Tory P. Sullivan
North Miami Beach Florida, 33162, United States
Marietta Dermatology Clinical Research, Inc.
Marietta Georgia, 30060, United States
MedaPhase, Inc.
Newnan Georgia, 30263, United States
Northwestern University
Chicago Illinois, 60611, United States
RUSH University
Chicago Illinois, 60612, United States
Dawes-Fretzin Clinical Research Group, LLC
Indianapolis Indiana, 46256, United States
Kansas City Dermatology, PA
Overland Park Kansas, 66215, United States
Beacon Clinical Research
Quincy Massachusetts, 02169, United States
HFMC New Center One
Detroit Michigan, 48202, United States
The Grekin Skin Institute
Warren Michigan, 48088, United States
Respiratory Medicine Research Institute of Michigan, PLC
Ypsilanti Michigan, 48197, United States
Clinical Studies Group
Henderson Nevada, 89074, United States
Psoriasis Treatment Center of Central New Jersey
East Windsor New Jersey, 08520, United States
Corning Center for Clinical Research
Corning New York, 14830, United States
Icahn School of Medicine at Mount Sinai
New York New York, 10029, United States
Sadick Dermatology
New York New York, 10075, United States
Wake Forest University Health Sciences
Winston-Salem North Carolina, 27157, United States
University of Cincinnati Health Physicians Office
Cincinnati Ohio, 45267, United States
Wright State Physicians
Fairborn Ohio, 45324, United States
Aventiv Research Inc.
Westerville Ohio, 43082, United States
Oregon Dermatology and Research Center
Portland Oregon, 97210, United States
Paddington Testing Company, Inc.
Philadelphia Pennsylvania, 19103, United States
Yardley Dermatology Associates
Yardley Pennsylvania, 19067, United States
Clinical Research Center of the Carolinas
Charleston South Carolina, 29407, United States
Rivergate Dermatology Clinical Research Center
Goodlettsville Tennessee, 37072, United States
Bellaire Dermatology Associates
Bellaire Texas, 77401, United States
Modern Research Associates, PLLC
Dallas Texas, 75231, United States
Austin Institute for Clinical Research, Inc.
Pflugerville Texas, 78660, United States
Progressive Clinical Research
San Antonio Texas, 78213, United States
Woden Dermatology Pty Ltd.
Phillip Australian Capital Territory, 2606, Australia
Skin & Cancer Foundation Australia
Darlinghurst New South Wales, 2010, Australia
St. George Dermatology and Skin Cancer Center
Kogarah New South Wales, 2217, Australia
Veracity Clinical Research
Woolloongabba Queensland, 4102, Australia
Skin & Cancer Foundation Inc.
Carlton Victoria, 3053, Australia
Sinclair Dermatology
East Melbourne Victoria, 3002, Australia
Burswood Dermatology
Victoria Park Western Australia, 6100, Australia
Dr. Chih-ho Hong Medical
Surrey British Columbia, V3R 6, Canada
Enverus Medical Research
Surrey British Columbia, V3V 0, Canada
Pacific Derm
Vancouver British Columbia, V6H 4, Canada
Winnipeg Clinic
Winnipeg Manitoba, R3C 0, Canada
Wiseman Dermatology Research
Winnipeg Manitoba, R3M 3, Canada
Brunswick Dermatology Centre
Fredericton New Brunswick, E3B 1, Canada
Nexus Clinical Research
St. John's Newfoundland and Labrador, A1A 5, Canada
Eastern Canada Cutaneous Research
Halifax Nova Scotia, B5H 1, Canada
Kingsway Clinical Research
Etobicoke Ontario, M8X 1, Canada
Guenther Derm Research Centre
London Ontario, N6A 3, Canada
Lynderm Research Inc.
Markham Ontario, L3P 1, Canada
DermEdge Research
Mississauga Ontario, L5H 1, Canada
Dermatology & Cosmetic Surgery
North Bay Ontario, P1B 3, Canada
Derm Clinic of Dr. Robern
Ottawa Ontario, K2G 6, Canada
Skin Centre for Dermatology
Peterborough Ontario, K9J 5, Canada
Dermatology & Cosmetic Surgery
Richmond Hill Ontario, L4B 1, Canada
K. Papp
Waterloo Ontario, N2J 1, Canada
XLR8 Medical Research
Windsor Ontario, N8W 1, Canada
Dr. David Gratton Dermatologue
Montréal Quebec, H3H 1, Canada
CRDQ
Québec Quebec, G1V 4, Canada
Aarhus University Hospital
Aarhus , , Denmark
Bispebjerg Hospital
Hellerup , , Denmark
Gentofte Hospital
Hellerup , , Denmark
Spedali Civili Brescia
Brescia , 25123, Italy
Policlinico-Vittorio Emanuele
Catania , 95123, Italy
Opedale San Salvatore
L'Aquila , 67100, Italy
AOU Pisa
Pisa , 56126, Italy
IRCCS San Gallicano
Rom , 00144, Italy
Policlinico "Agostino Gemelli"
Rom , 00168, Italy
Istituto Clinico Humanitas
Rozzano , 20089, Italy
Pusan National University Hospital
Busan , 49241, Korea, Republic of
Chungnam National Univeristy
Daejeon , 35015, Korea, Republic of
Chonnam National University Hospital
Gwangju , 61469, Korea, Republic of
Soon Chun Hyang University Hospital
Gyeonggi-do , 14584, Korea, Republic of
Korea University Ansan Hospital
Gyeonggi-do , 425-7, Korea, Republic of
St. Mary's Hospital
Incheon , 21431, Korea, Republic of
Inha University Hospital
Incheon , 22332, Korea, Republic of
Seoul National University Hospital
Seoul , 03080, Korea, Republic of
Yonsei University Health Syste
Seoul , 03722, Korea, Republic of
Konkuk University Medical Center
Seoul , 05030, Korea, Republic of
Chung-Ang University Hospital
Seoul , 06973, Korea, Republic of
Hallym University Kangnam Sacr
Seoul , 07441, Korea, Republic of
Centrum Medyczne Gdynia
Gdynia , 81-33, Poland
Synexus Polska Gdyni
Gdynia , 81-38, Poland
Synexus Polska Katowicach
Katowice , 40-04, Poland
Centrum Medyczne PRATIA
Kraków , 30-00, Poland
Krakowskie Centrum Medyczne
Kraków , 31-50, Poland
Synexus Polska Poznaniu
Poznań , 60-70, Poland
Klinika Dermatologii
Rzeszów , 35-05, Poland
"DERMED" Centrum Medyczne Sp.
Łódź , 90-26, Poland
Dermoklinika Centrum Medyczne
Łódź , 90-43, Poland
Chelyabinsk Dermat. Dispensary
Chelyabinsk , 45404, Russian Federation
Federal State Budgetary Institution State Sci. Ctr.
Moscow , 10707, Russian Federation
French clinic of skin diseases
Saint Petersburg , 19112, Russian Federation
Military Medical Academy
Saint Petersburg , 19404, Russian Federation
Ninewells Hospital
Dundee Angus, DD2 1, United Kingdom
Salford Royal Hospital
Salford Greater Manchester, M6 8H, United Kingdom
Whipps Cross University Hospital
Leytonstone London, E11 1, United Kingdom
Harrogate District Hospital
Harrogate North Yorkshire, HG2 7, United Kingdom
Royal Hallamshire Hospital
Sheffield South Yorkshire, S10 2, United Kingdom
East Surrey Hospital
Redhill Surrey, RH1 5, United Kingdom
Royal Victoria Infirmary
Newcastle upon Tyne Tyne And Wear, NE1 4, United Kingdom
Russells Hall Hospital
Dudley West Midlands, DY1 2, United Kingdom
Walsall Healthcare NHS Trust
Walsall West Midlands, WS2 9, United Kingdom
Chapel Allerton Hospital
Leeds West Yorkshire, LS7 4, United Kingdom
West Suffolk Hospital
Bury St Edmunds , IP33 , United Kingdom
The Whittington Hospital NHS
London , N19 5, United Kingdom
Guy's Hospital
London , SE1 9, United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Psoriasis

Phase:

Phase 3

Estimated Enrollment:

794

Study ID:

NCT03160885

Recruitment Status:

Completed

Sponsor:


LEO Pharma

How clear is this clinincal trial information?

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