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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03160885




Registration number
NCT03160885
Ethics application status
Date submitted
18/05/2017
Date registered
19/05/2017

Titles & IDs
Public title
Tralokinumab Monotherapy for Moderate to Severe Atopic Dermatitis - ECZTRA 2 (ECZema TRAlokinumab Trial no. 2)
Scientific 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
Secondary ID [1] 0 0
2016-004201-13
Secondary ID [2] 0 0
LP0162-1326
Universal Trial Number (UTN)
Trial acronym
ECZTRA 2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atopic Dermatitis 0 0
Condition category
Condition code
Skin 0 0 0 0
Dermatological conditions
Skin 0 0 0 0
Other skin conditions
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tralokinumab
Treatment: Drugs - Placebo

Experimental: Initial treatment period - Tralokinumab Q2W - Week 0 to Week 16

Two subcutaneous (SC) injections of tralokinumab as a loading dose on Day 0, followed by a SC injection of tralokinumab Q2W regimen for 16 weeks

Placebo comparator: Initial treatment period - Placebo - Week 0 to Week 16 (Initial treatment period):

Two subcutaneous (SC) injections of placebo as a loading dose on Day 0 followed by a SC injection of placebo Q2W regimen for 16 weeks

Experimental: Maintenance treatment period - Tralokinumab Q2W - Week 16 to Week 52

Tralokinumab responders from the initial treatment period re-randomised at Week 16 and administered tralokinumab maintenance subcutaneous injection regimen Q2W for 36 weeks

Experimental: Maintenance treatment period - Tralokinumab Q4W - Week 16 to Week 52

Tralokinumab responders from the initial treatment period re-randomised at Week 16 and administered tralokinumab maintenance subcutaneous injection regimen Q4W for 36 weeks.

Participants in this group receive alternating doses of tralokinumab SC injection and placebo SC injection every 2 weeks

Placebo comparator: Maintenance treatment period - Placebo - Week 16 to Week 52

Tralokinumab responders from initial treatment period randomised at Week 16 and administered placebo subcutaneous maintenance injection for 36 weeks

Placebo comparator: Maintenance treatment period - Placebo (tralokinumab naive) - Week 16 to Week 52

Placebo responders from the initial treatment period re-assigned at Week 16 and administered placebo maintenance subcutaneous injection regimen Q2W for 36 weeks

Experimental: Open-label treatment - Tralokinumab 300 mg Q2W + optional TCS - Week 16 to Week 52

Subjects receiving initial treatment with tralokinumab Q2W or placebo Q2W assigned to open-label treatment at Week 16 and administered tralokinumab subcutaneous (SC) injection + optional TCS\* regimen Q2W

OR

Subjects receiving maintenance treatment with tralokinumab Q2W/Q4W or placebo assigned to open-label treatment after Week 16 and administered tralokinumab SC injection + optional TCS regimen Q2W

• TCS = topical corticosteroids


Treatment: Drugs: 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

Treatment: Drugs: Placebo
Placebo contains the same excipients, in the same concentration only lacking tralokinumab
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16.
Timepoint [1] 0 0
At Week 16
Primary outcome [2] 0 0
Subjects Achieving at Least 75% Reduction in Eczema Area and Severity Index [EASI].
Timepoint [2] 0 0
At Week 16
Secondary outcome [1] 0 0
Reduction of Worst Daily Pruritus Numeric Rating Scale (Weekly Average) of at Least 4 From Baseline to Week 16.
Timepoint [1] 0 0
Week 0 to Week 16
Secondary outcome [2] 0 0
Change in Scoring Atopic Dermatitis (SCORAD) From Baseline to Week 16.
Timepoint [2] 0 0
Week 0 to Week 16
Secondary outcome [3] 0 0
Change in Dermatology Life Quality Index (DLQI) Score From Baseline to Week 16.
Timepoint [3] 0 0
Week 0 to Week 16
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
At Week 52
Secondary outcome [5] 0 0
Subjects With at Least 75% Reduction in Eczema Area and Severity Index [EASI] at Week 52 Among Subjects With EASI75 at Week 16
Timepoint [5] 0 0
At Week 52
Secondary outcome [6] 0 0
Safety and Tolerability: Adverse Event (AE) /Serious Adverse Event (SAE) Frequency
Timepoint [6] 0 0
Week 0 to Week 16
Secondary outcome [7] 0 0
Frequency of Anti-drug Antibodies
Timepoint [7] 0 0
Week 0 to Week 16
Secondary outcome [8] 0 0
Subjects Achieving at Least 50% Reduction in Eczema Area and Severity Index [EASI] at Week 16
Timepoint [8] 0 0
At Week 16
Secondary outcome [9] 0 0
Subjects Achieving at Least 90% Reduction in Eczema Area and Severity Index [EASI] at Week 16.
Timepoint [9] 0 0
At Week 16
Secondary outcome [10] 0 0
Change From Baseline to Week 16 in Eczema Area and Severity Index [EASI] Score
Timepoint [10] 0 0
At Week 16
Secondary outcome [11] 0 0
Subjects Achieving at Least 75% Reduction in Scoring Atopic Dermatitis (SCORAD) at Week 16.
Timepoint [11] 0 0
At Week 16
Secondary outcome [12] 0 0
Subjects Achieving at Least 50% Reduction in Scoring Atopic Dermatitis (SCORAD) at Week 16.
Timepoint [12] 0 0
At Week 16
Secondary outcome [13] 0 0
Change From Baseline to Week 16 in Worst Daily Pruritus NRS (Weekly Average).
Timepoint [13] 0 0
Baseline to Week 16
Secondary outcome [14] 0 0
Reduction of Worst Daily Pruritus NRS (Weekly Average) =3 From Baseline to Week 16.
Timepoint [14] 0 0
Baseline to Week 16
Secondary outcome [15] 0 0
Reduction From Baseline to Week 16 of Dermatology Life Quality Index (DLQI) of =4 Points Among Subjects With Baseline DLQI =4.
Timepoint [15] 0 0
Baseline to Week 16

Eligibility
Key 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).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/06/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
14/08/2019
Sample size
Target
Accrual to date
Final
794
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Woden Dermatology Pty Ltd. - Phillip
Recruitment hospital [2] 0 0
Skin & Cancer Foundation Australia - Darlinghurst
Recruitment hospital [3] 0 0
St. George Dermatology and Skin Cancer Center - Kogarah
Recruitment hospital [4] 0 0
Veracity Clinical Research - Woolloongabba
Recruitment hospital [5] 0 0
Skin & Cancer Foundation Inc. - Carlton
Recruitment hospital [6] 0 0
Sinclair Dermatology - East Melbourne
Recruitment hospital [7] 0 0
Burswood Dermatology - Victoria Park
Recruitment postcode(s) [1] 0 0
2606 - Phillip
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [5] 0 0
3053 - Carlton
Recruitment postcode(s) [6] 0 0
3002 - East Melbourne
Recruitment postcode(s) [7] 0 0
6100 - Victoria Park
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
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United States of America
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California
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Florida
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Georgia
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Illinois
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Indiana
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Kansas
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Massachusetts
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Michigan
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Nevada
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New Jersey
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New York
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North Carolina
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Ohio
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Oregon
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Pennsylvania
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South Carolina
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Tennessee
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Texas
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Canada
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British Columbia
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Canada
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Manitoba
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Canada
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New Brunswick
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Canada
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Newfoundland and Labrador
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Canada
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Nova Scotia
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Canada
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Ontario
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Canada
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Quebec
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Denmark
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Aarhus
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Denmark
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Hellerup
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Italy
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Brescia
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Italy
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Catania
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Italy
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L'Aquila
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Italy
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Pisa
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Italy
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Rom
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Italy
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Rozzano
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Korea, Republic of
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Busan
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Korea, Republic of
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Daejeon
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Korea, Republic of
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Gwangju
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Korea, Republic of
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Gyeonggi-do
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Korea, Republic of
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Incheon
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Korea, Republic of
State/province [40] 0 0
Seoul
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Poland
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Gdynia
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Poland
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Katowice
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Poland
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Kraków
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Poland
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Poznan
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Poland
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Rzeszów
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Poland
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Lódz
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Russian Federation
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Chelyabinsk
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Russian Federation
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Moscow
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Russian Federation
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Saint Petersburg
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United Kingdom
State/province [50] 0 0
Angus
Country [51] 0 0
United Kingdom
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Greater Manchester
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United Kingdom
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London
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United Kingdom
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North Yorkshire
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United Kingdom
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South Yorkshire
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United Kingdom
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Surrey
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United Kingdom
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Tyne And Wear
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United Kingdom
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West Midlands
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United Kingdom
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West Yorkshire
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United Kingdom
State/province [59] 0 0
Bury St Edmunds

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
LEO Pharma
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Eric Simpson, MD, MCR
Address 0 0
Department of Dermatology, Oregon Health and Science University
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?


Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
Available to whom?
De-identified Individual Participant Data can be made available to researchers and is subject to approved scientifically sound research proposal and signed data-sharing agreement.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://leopharmatrials.com/en/for-researchers


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03160885