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NCT03761537
11.2.4
Body surface area involvement
11.2.4 Body surface area involvement The total body surface area (BSA) affected by AD will be assessed by the investigator for each section of the body as component A of SCORAD (see Section 11.3.3) and will be reported as a percentage of all major body sections combined. The following body regions will be assessed (bra...
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NCT03761537
11.2.5
Columbia-Suicide Severity Rating Scale
11.2.5 Columbia-Suicide Severity Rating Scale The C-SSRS is a rater-administered instrument used to assess the lifetime history and severity of suicidal ideation and suicidal behaviour through a series of simple, plain-language questions (24, 25). The C-SSRS must be completed at the screening visit to check that ![](pa...
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NCT03761537
11
3Efficacy assessments
11.3Efficacy assessments
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NCT03761537
11.3.1
Investigator's Global Assessment
11.3.1 Investigator's Global Assessment 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) (Panel 7; 26). The IGA score will be assessed according to the schedule of trial procedures (Section 4). The asses...
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NCT03761537
11.3.2
Eczema Area and Severity Index
11.3.2 Eczema Area and Severity Index The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD (27). The EASI score will be assessed according to the schedule of trial procedures (Section 4). The assessment will be based on the condition of the disease at the...
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NCT03761537
11.3.3
SCORing Atopic Dermatitis
11.3.3 SCORing Atopic Dermatitis The SCORAD is a validated tool to evaluate the extent and severity of AD lesions, along with subjective symptoms (28). The maximum total score is 103, with higher values indicating more severe disease. SCORAD will be assessed according to the schedule of trial procedures (Section 4). Th...
[ "Extent (A)", "Intensity (B)", "Subjective symptoms (C)" ]
NCT03761537
11.3.4
Patient-reported outcomes
11.3.4 Patient-reported outcomes All PROs included in this trial are included in the investigator trial file.
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NCT03761537
11.3.4.1
Eczema-related Sleep numeric rating scale
11.3.4.1 Eczema-related Sleep numeric rating scale Subjects will rate how much their eczema interfered with their sleep the last night using an 11-point NRS (0 indicating that it 'did not interfere' and 10 indicating that it 'completely interfered'). Subjects will complete the Eczema-related Sleep NRS as part of an eDi...
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NCT03761537
11.3.4.2
Worst Daily Pruritus numeric rating scale
11.3.4.2 Worst Daily Pruritus numeric rating scale 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'. Subjects will complete the Worst Daily Pruritus NRS as part of an eDiary each...
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NCT03761537
11.3.4.3
Patient Days of Topical Treatment Use
11.3.4.3 Patient Days of Topical Treatment Use Subjects will assess their use of topical AD treatment over the past 24 hours using a response scale ('yes', 'no'). Subjects will complete the Patient Days of Topical Treatment Use as part of an eDiary each day in the morning from baseline (Week 0 [visit 3]) until Week 26.
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NCT03761537
11.3.4.4
SF-36
11.3.4.4 SF-36 The SF-36 (version 2, Acute Recall) is a 36-item general health status assessment. Subjects will be asked to answer each question by selecting one of 3 to 6 categorical response options. The instrument instructions do not state a specific recall period; however, a recall period is defined within most ite...
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NCT03761537
11.3.4.5
Patient-Oriented Eczema Measure
11.3.4.5 Patient-Oriented Eczema Measure The POEM is a validated questionnaire used to assess disease symptoms in atopic eczema patients in both clinical practice and clinical trials (31). The tool consists of 7 items each addressing a specific symptom (itching, sleep, bleeding, weeping, cracking, flaking, and dryness)...
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NCT03761537
11.3.4.6
Dermatology Life Quality Index
11.3.4.6 Dermatology Life Quality Index 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 HRQoL over the last week such as dermatologyrelated symp...
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NCT03761537
11.3.4.7
EQ-5D-5L
11.3.4.7 EQ-5D-5L The EQ-5D-5L is a standardised measure of health status developed by the EuroQoL group to provide a simple, generic measure of health for clinical and economic appraisal (33). The EQ-5D-5L is a self-administered questionnaire used to assess health status 'today' and is divided into 2 sections: The fir...
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NCT03761537
11.3.4.8
Hospital Anxiety and Depression Scale
11.3.4.8 Hospital Anxiety and Depression Scale The HADS is a Likert scale tool widely used to detect states of anxiety and depression in a general hospital setting (34). The tool consists of 14 items that assess the subject's anxiety (7 items) and depression (7 items) during the last week. Each question is scored from ...
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NCT03761537
11.4
Safety assessments
11.4 Safety assessments
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NCT03761537
11.4.1
Vital signs
11.4.1 Vital signs Vital signs (resting blood pressure, pulse, and body temperature) must be assessed according to the schedule of trial procedures (Section 4). Vital signs will be measured in a supine or sitting position following at least 5 minutes of rest. For the first 3 IMP dosing visits (i.e., Weeks 0, 2, and 4),...
[ "Reporting in eCRF" ]
NCT03761537
11.4.2
Physical examination
11.4.2 Physical examination A thorough physical examination of the subject including whole body inspection of the skin; auscultation of heart, lungs, and abdomen; palpation of the abdominal organs; and basic neurological status must be performed according to the schedule of trial procedures (Section 4). If an unaccepta...
[ "Reporting in eCRF" ]
NCT03761537
11.4.3
Electrocardiogram
11.4.3 Electrocardiogram A single 12-lead resting digital ECG will be recorded after the subject has been supine for at least 5 minutes at the visits indicated in the schedule of trial procedures (Section 4). A pre-evaluation of the ECGs will be performed by the investigators to evaluate immediate subject safety. As a ...
[ "Reporting in eCRF" ]
NCT03761537
11.4.4
Laboratory testing
11.4.4 Laboratory testing
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NCT03761537
11.4.4.1
Overview
11.4.4.1 Overview Blood and urine samples will be collected according to the schedule of trial procedures (Section 4). The evaluations shown in Panel 10 will be performed. ![](page80Picture11.jpeg) Panel 10: Clinical laboratory tests | Chemistry | Haematology | |----------------------------|---------------------------...
[ "Panel 10: Clinical laboratory tests" ]
NCT03761537
11.4.4.2
Investigator evaluation of laboratory samples
11.4.4.2 Investigator evaluation of laboratory samples Central laboratory Chemistry, haematology, urinalysis (if applicable), serology, and serum pregnancy tests will be analysed by a central laboratory which will provide results to the trial sites. The investigator must evaluate all results outside the reference rang...
[ "Central laboratory", "Tests performed at the trial site", "Reporting in eCRF" ]
NCT03761537
11.4.5
Anti-drug antibody measurements
11.4.5 Anti-drug antibody measurements Blood samples will be collected to determine ADA levels at pre-determined time points according to the schedule of trial procedures (Section 4). It will be recorded in the eCRF if the sample was taken; if not, a reason will be provided. Collection, handling, and shipment instructi...
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NCT03761537
11.5
Pharmacokinetic assessments
11.5 Pharmacokinetic assessments Blood samples for PK assessments will be collected at the time points specified in the schedule of trial procedures (Section 4). It will be recorded in the eCRF if the PK sample was taken; if not, a reason will be provided. Collection, handling, and shipment instructions for PK blood sa...
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NCT03761537
11.6
Other assessments
11.6 Other assessments
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NCT03761537
11.6.1
Photography
11.6.1 Photography At selected trial sites, subjects will be asked to participate in a photography component involving digital photography assessments to show disease progression over time. Participation in this photography component requires that the subject provides additional informed consent. Digital colour photogr...
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NCT03761537
11
7Estimate of total blood volume collected
11.7Estimate of total blood volume collected Blood samples will be drawn for haematology, biochemistry, serology, PK, and ADA. The total volume of blood to be drawn is approximately 160 mL, which is less than the volume of blood drawn during a blood donation (approximately 500 mL).
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NCT03761537
11.8
End of trial
11.8 End of trial An end-of-treatment form and an end-of-trial form will be completed in the eCRF for all randomised subjects, including subjects who permanently discontinue IMP and subjects who withdraw from the trial (see Section 10.3 for early termination assessments). ![](page84Picture14.jpeg) End-of-treatment for...
[ "End-of-treatment form", "End-of-trial form" ]
NCT03761537
11.9
Storage of biological samples
11.9 Storage of biological samples PK samples will be retained for as long as the quality of the material permits evaluation but for no longer than 12 months after completion of the clinical trial report (CTR). Samples for ADA evaluation will be retained for as long as the quality of the material permits evaluation but...
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NCT03761537
12
Scientific rationale for trial design and appropriateness of assessments
12 Scientific rationale for trial design and appropriateness of assessments Scientific rationale for trial design The trial is designed to evaluate the efficacy of tralokinumab in combination with TCS compared to placebo in combination with TCS in treating severe AD in subjects who are not adequately controlled with o...
[ "Scientific rationale for trial design", "Appropriateness of assessments" ]
NCT03761537
13
Adverse events
13 Adverse events
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NCT03761537
13.1
Definition and classification of adverse events
13.1 Definition and classification of adverse events Adverse events (AEs) and serious adverse events (SAEs) are defined in Appendix 1. Classification of AEs in terms of severity, causality and outcome is defined in Appendix 2.
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NCT03761537
13.2
Collection of adverse event reports
13.2 Collection of adverse event reports AEs must be collected from time of first trial-related activity after the subject has signed the informed consent form (ICF) until completion of the clinical trial (defined as the safety follow-up visit 16 weeks after last IMP injection). For subjects entering the long-term exte...
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NCT03761537
13.3
Reporting of adverse events
13.3 Reporting of adverse events AEs reported by the subject or observed by the investigator must be recorded on the AE form of the eCRF and should be described in the following manner: The AE term must be in precise English medical terminology (i.e. not necessarily the exact words used by the subject). Whenever possib...
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NCT03761537
13.4
Reporting of serious adverse events
13.4 Reporting of serious adverse events The criteria that define an AE as serious (that is, an SAE) are defined in Appendix 1. SAE criteria are also listed on the SAE form.
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NCT03761537
13.4.1
Investigator reporting responsibilities
13.4.1 Investigator reporting responsibilities Any SAE must be reported to LEO on the (paper) SAE Form within 24 hours of first knowledge. This report should contain an assessment of available information on seriousness, severity, causal relationship to the trial product/ trial procedure, the action taken, the outcome ...
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NCT03761537
13.4.2
LEO reporting responsibilities
13.4.2 LEO reporting responsibilities Global Safety at LEO is responsible for assessing whether or not an SAE is expected. The relevant reference safety information document for this clinical trial is: - x For the IMP, the Investigator's Brochure, current edition, must be used. - x For the AxMP (mometasone furoate, 0.1...
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NCT03761537
13
5Other events that require expedited reporting: pregnancy
13.5Other events that require expedited reporting: pregnancy Any pregnancy occurring during the clinical trial must be reported to LEO within 24 hours of first knowledge using the (paper) Pregnancy Form (Part I). All pregnancies must be followed up until delivery or termination and final outcome must be reported on the...
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NCT03761537
13.6
Reporting of other events
13.6 Reporting of other events
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NCT03761537
13.6.1
Adverse events of special interest
13.6.1 Adverse events of special interest The events listed in Panel 11 are considered AEs of special interest (AESIs) in this trial and will require additional details to be recorded in the eCRF. LEO may request that the investigator forward test results, as appropriate. An AESI may be serious (requiring expedited rep...
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NCT03761537
13.6.2
Overdose
13.6.2 Overdose An overdose is defined as a subject receiving a dose of IMP in excess of that specified in this protocol. The term 'overdose' including a specification of why it occurred (accidental or intentional) must be documented on the AE form of the eCRF. In addition, AEs originating ![](page91Picture8.jpeg) Page...
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NCT03761537
13.6.3
Medication error
13.6.3 Medication error Medication error refers to any unintentional error in the dispensing or administration of an IMP while in the control of the investigator or subject. Broadly, medication errors fall into 4 categories: wrong medication, wrong dose (including strength, form, concentration, amount), wrong route of ...
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NCT03761537
13.6.4
Misuse
13.6.4 Misuse Misuse refers to situations where the IMP is intentionally and inappropriately used not in accordance with the protocol. The term 'misuse' must be documented on the AE form in the eCRF. In addition, AEs originating from misuse must be documented on a separate line. If the AE originating from misuse qualif...
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NCT03761537
13.6.5
Abuse
13.6.5 Abuse Abuse relates to the sporadic or persistent, intentional excessive use of an IMP which is accompanied by harmful physical or psychological effects. The term 'abuse' must be documented on the AE form in the eCRF. In addition, AEs originating from abuse must be documented on a separate line. If the AE origin...
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NCT03761537
13.6.6
Aggravation of condition
13.6.6 Aggravation of condition Any clinically significant aggravation/exacerbation/worsening of any medical condition(s), compared to screening must be reported as an AE. If the AE originating from aggravation of a condition qualifies as an SAE, expedited reporting is required (Section 13.4). ![](page92Picture14.jpeg)...
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NCT03761537
13
7Follow-up for final outcome of adverse events
13.7Follow-up for final outcome of adverse events During the trial, the investigator should follow up for final outcome on all AEs (including SAEs). Once a subject leaves the clinical trial, the investigator should follow up on the outcome of all non-serious AEs classified as of possible/probable relationship to the IM...
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NCT03761537
13
8Handling of an urgent safety measure
13.8Handling of an urgent safety measure An urgent safety measure is a measure taken to implement an action/protocol deviation under an emergency. This is defined as "…the occurrence of any new event relating to the conduct of the trial or the development of the investigational medicinal product where that new event is...
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NCT03761537
14
Statistical methods
14 Statistical methods
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NCT03761537
14.1
Sample size
14.1 Sample size With a significance level of 5%, a sample size of 250 subjects will provide 99% power for detecting a treatment difference for the primary endpoint, assuming an EASI75 response rate at Week 16 of 40% vs 15% for tralokinumab+TCS and placebo+TCS, respectively. Assuming a response rate of 30% vs 15% in re...
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NCT03761537
14
2Trial analysis sets
14.2Trial analysis sets All screened subjects will be accounted for in the CTR. All subjects randomised to treatment and exposed to the IMP will be included in the full analysis set (FAS) and will be analysed for efficacy. Exclusions from the FAS can be considered in special cases as described in the ICH E9 guideline, ...
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NCT03761537
14.3
Statistical analysis
14.3 Statistical analysis
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NCT03761537
14.3.1
Aspects related to the COVID-19 pandemic
14.3.1 Aspects related to the COVID-19 pandemic As the implications of the COVID-19 pandemic will, extraordinarily, influence trial events and data in manners not foreseen by the protocol, this section is introduced to elaborate on the COVID-19 pandemic related aspects that may require special handling depending on the...
[ "x Permanent discontinuation of IMP due to the COVID-19 pandemic:", "x Use of rescue treatment due to unavailability of IMP related to the COVID-19 pandemic:", "x Prolonged interruption of IMP dosing due to the COVID-19 pandemic:", "x Missing data due to the COVID-19 pandemic:", "x Infection with COVID-19:"...
NCT03761537
14.3.2
Disposition of subjects
14.3.2 Disposition of subjects For all randomised subjects the reasons for permanent discontinuation of IMP and for withdrawal from the trial will be presented by treatment group. Permanent discontinuation of IMP due to the COVID-19 pandemic will be added to the list of reasons and identified based on the information d...
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NCT03761537
14.3.3
Demographics and other baseline characteristics
14.3.3 Demographics and other baseline characteristics Descriptive statistics of demographics and other baseline characteristics will be presented for all randomised subjects. The presentations will be overall and by treatment group. Demographics (age, sex, race, and ethnicity) and baseline disease characteristics (IGA...
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NCT03761537
14.3.4
Exposure and treatment compliance
14.3.4 Exposure and treatment compliance Exposure Exposure to treatment will be presented for the safety analysis set as days of exposure per treatment group. Treatment compliance Compliance to treatment regimen will be recorded in the eCRF. If any complications or deviations in administration are observed, these wil...
[ "Exposure", "Treatment compliance" ]
NCT03761537
14.3.5
Rescue treatment
14.3.5 Rescue treatment Rescue treatment will be defined by the following algorithm: Concomitant medications with 'Dermatitis atopic' or 'Dermatitis infected' as the preferred term (PT) for the indication, and either of the following: - x ATC2 code H02 - x Preferred name Methotrexate, Methotrexate sodium, Ciclosporin, ...
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NCT03761537
14.3.6
Testing strategy
14.3.6 Testing strategy The primary and secondary endpoints will be evaluated hierarchically in the order shown in Panel 12. The hypothesis relating to a specific endpoint cannot be rejected unless all hypotheses relating to endpoints earlier in the hierarchy are also rejected at the 5% significance level. Hypothesis t...
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NCT03761537
14.3.7
Intercurrent events
14.3.7 Intercurrent events The applied estimands incorporate the following 3 main subject-specific intercurrent events that influence how the treatment effects are estimated. x Initiation of rescue treatment: Some of the estimands use the initiation of rescue treatment as an event that modifies the applied value of an...
[ "x Initiation of rescue treatment:", "x Permanent discontinuation of IMP:", "x Subject-onset of the COVID-19 pandemic:", "x Missing data due to the COVID-19 pandemic:" ]
NCT03761537
14.3.8
Analysis of primary efficacy endpoint
14.3.8 Analysis of primary efficacy endpoint 4 estimands addressing different aspects of the trial objectives will be defined for the primary efficacy endpoint (Panel 13): x Primary estimand: 'COVID-19 modified composite' x Secondary estimand: 'composite' x Tertiary estimand: 'treatment policy' x Quaternary estimand: '...
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NCT03761537
14.3.8.1
Primary estimand: 'COVID-19 modified composite'
14.3.8.1 Primary estimand: 'COVID-19 modified composite' The primary estimand for the primary endpoint will be: x Treatment difference in response rates of EASI75 after 16 weeks achieved without rescue treatment and treatment discontinuation, as if the COVID-19 pandemic did not happen The primary estimand assesses the ...
[ "Primary analysis for the primary estimand", "Sensitivity analysis for the primary estimand" ]
NCT03761537
14.3.8.2
Secondary estimand: 'composite'
14.3.8.2 Secondary estimand: 'composite' The secondary estimand for the primary endpoint will be: x Treatment difference in response rates of EASI75 after 16 weeks achieved without either rescue treatment or treatment discontinuation, as if the COVID-19 pandemic did not happen The secondary estimand assesses the expect...
[ "Primary analysis for the secondary estimand", "Sensitivity analyses for the secondary estimand" ]
NCT03761537
14.3.8.3
Tertiary estimand: 'treatment policy'
14.3.8.3 Tertiary estimand: 'treatment policy' The tertiary estimand for the primary endpoint will be: ![](page105Picture12.jpeg) Page 106 of 170 x Treatment difference in response rate of EASI75 after 16 weeks between tralokinumab+TCS and placebo+TCS regardless of rescue treatment and IMP discontinuation, as if the CO...
[ "Primary analysis for the tertiary estimand", "Sensitivity analyses for the tertiary estimand" ]
NCT03761537
14.3.8.4
Quaternary estimand: 'hypothetical'
14.3.8.4 Quaternary estimand: 'hypothetical' The quaternary estimand for the primary endpoint will be: x Treatment difference in response rates of EASI75 after 16 weeks if all subjects adhered to the treatment regimen in the sense that they did not discontinue IMP permanently, no rescue treatment was made available, an...
[ "Primary analysis of the quaternary estimand", "EASI75 responder imputation", "Analysis of Week 16 response", "Sensitivity analysis for the quaternary estimand" ]
NCT03761537
14.3.9
Analysis of secondary endpoints
14.3.9 Analysis of secondary endpoints The secondary endpoints evaluate the impact of 16 and 26 weeks of treatment on (i) itch, (ii) severity and extent of AD, and (iii) HRQoL. The corresponding endpoints are (i) reduction (yes/no) of Worst Daily Pruritus NRS average score for the past week (hereinafter 'Worst Daily Pr...
[ "Subgroup analysis of binary endpoints", "IGA 0/1 responder imputation" ]
NCT03761537
14.3.9.1
Primary estimand for the continuous secondary endpoints: 'hypothetical'
14.3.9.1 Primary estimand for the continuous secondary endpoints: 'hypothetical' The primary estimand for the continuous secondary endpoints will be: x Treatment difference in change from baseline to Week 16/ Week 26 in SCORAD and DLQI scores, respectively, if all subjects adhered to the treatment regimen in the sense ...
[ "Primary analysis of the primary estimand (continuous secondary endpoints)", "Sensitivity analysis for the primary estimand (continuous secondary endpoints)" ]
NCT03761537
14.3.9.2
Secondary estimand for the continuous secondary endpoints: 'treatment policy'
14.3.9.2 Secondary estimand for the continuous secondary endpoints: 'treatment policy' The secondary estimand for the continuous secondary endpoints will be: x Treatment difference in change from baseline to Week 16/ Week 26 in SCORAD and DLQI scores, respectively, between tralokinumab+TCS and placebo+TCS regardless of...
[ "Primary analyses for the secondary estimand (continuous secondary endpoints)", "Sensitivity analyses for the secondary estimand (continuous secondary endpoints)" ]
NCT03761537
14.3.9.3
Tertiary estimand for the continuous secondary endpoints: 'COVID-19 modified composite'
14.3.9.3 Tertiary estimand for the continuous secondary endpoints: 'COVID-19 modified composite' The primary estimand for the continuous tertiary endpoint will be: x Treatment difference in change from baseline to Week 16/Week 26 in SCORAD and DLQI scores, respectively, without rescue treatment and treatment discontinu...
[ "Primary analysis for the tertiary estimand (continuous secondary endpoints)" ]
NCT03761537
14.3.9.4
Subgroup analysis of continuous endpoints
14.3.9.4 Subgroup analysis of continuous endpoints Subgroup analyses will be performed for the SCORAD and DLQI endpoints at Week 16 and Week 26 for the following groups: sex, prior CSA use, baseline disease severity (IGA 3 or 4), country, age (≤65 years, >65 years) for the primary analysis of primary and secondary esti...
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NCT03761537
14.3.10
Analysis of other endpoints
14.3.10 Analysis of other endpoints All binary endpoints listed under 'Other endpoints' (Panel 4) will be analysed as for the primary analysis of the primary and secondary estimands for the primary endpoint and presented for the FAS at Week 16 and Week 26. All continuous endpoints listed under 'Other endpoints' (Panel ...
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NCT03761537
14.3.11
Analysis of exploratory supporting endpoints
14.3.11 Analysis of exploratory supporting endpoints There will be performed longitudinal analyses by visit/week of all primary, secondary and 'Other' efficacy endpoints, as specified in Panel 4. For the binary endpoints, the analyses will use the primary analysis of the primary estimand for each scheduled visit/week i...
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NCT03761537
14.3.12
Analysis of patient-reported outcomes
14.3.12 Analysis of patient-reported outcomes The PROs (POEM, DLQI, EQ-5D-5L [index and VAS scores], SF-36, and HADS) will be summarised by treatment group and visit using descriptive statistics based on the FAS. ![](page117Picture12.jpeg) Page 118 of 170 The PROs collected in the eDiaries on a daily basis (Worst Daily...
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NCT03761537
14.3.13
Analysis of safety
14.3.13 Analysis of safety The analyses of safety will be based on the safety analysis set and the safety follow-up analysis set.
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NCT03761537
14.3.13.1
Adverse events
14.3.13.1 Adverse events To assess the safety of tralokinumab in combination with TCS when used to treat severe AD for 26 weeks, the frequency of AEs and SAEs are included as additional secondary endpoints. AEs will be coded during the course of the trial according to Medical Dictionary for Regulatory Activities (MedDR...
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NCT03761537
14.3.13.2
Vital signs
14.3.13.2 Vital signs The change in vital signs (blood pressure, heart rate, body temperature) from baseline to each visit will be summarised by visit and treatment group as mean, standard deviation, median, 1st quartile, 3rd quartile, minimum, and maximum values for the safety analysis set. Vital signs will be listed ...
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NCT03761537
14.3.13.3
Clinical laboratory evaluation
14.3.13.3 Clinical laboratory evaluation The change in each of the laboratory parameters from baseline to each visit will be summarised by visit and treatment group as mean, standard deviation, median, 1st quartile, 3rd ![](page119Picture12.jpeg) quartile, minimum, and maximum values for the safety analysis set. Labora...
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NCT03761537
14.3.13.4
Anti-drug antibodies
14.3.13.4 Anti-drug antibodies The frequency of ADA is a secondary endpoint included to assess the safety and tolerability (immunogenicity) of tralokinumab in combination with TCS. ADA status at each visit will be summarised by treatment group. If considered relevant, descriptive statistics including number of subjects...
[ "x Positive", "x Perishing", "x No post-baseline ADA assessment." ]
NCT03761537
14.3.14
Pharmacokinetics
14.3.14 Pharmacokinetics All the PK samples in the trial are trough samples. The trough concentration (Ctrough) will be listed by treatment group and descriptive statistics will be applied. Ctrough values from subjects with positive ADA/nAB will be compared to values from subjects with negative ADA/nAB if data permits.
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NCT03761537
14.3.15
Interim analysis
14.3.15 Interim analysis No interim analysis is planned.
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NCT03761537
14.3.16
General principles
14.3.16 General principles Unless otherwise stated, all significance tests will be 2-sided using the 5% significance level. All CIs will be presented with 95% degree of confidence. An observed-cases approach will be used for tabulations of data by visit (i.e. involving only those subjects who attended each specific vis...
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NCT03761537
14.3.17
Handling of missing values
14.3.17 Handling of missing values Procedures for handling of missing values are included under the sections describing the individual analyses. ![](page122Picture3.jpeg)
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NCT03761537
15
References
15 References - 1. Silverberg JI, Hanifin JM. Adult eczema prevalence and associations with asthma and other health and demographic factors: a US population-based study. J Allergy Clin Immunol. 2013;132(5):1132–1138. - 2. Hanifin JM, Reed ML, Eczema Prevalence and Impact Working Group. A population based survey of ecze...
[ "Appendix 1: Definitions of adverse events and serious adverse events", "Adverse event definition", "This definition includes:", "Serious adverse event definition", "Appendix 2: Classification of adverse events", "Severity", "Causality", "Outcome", "Appendix 3: Trial governance considerations", "A...
NCT03784898
1
STUDY FLOW CHART
1 STUDY FLOW CHART | Assessments | Screening &Inclusion Visita | |-----------------------------------------------------------------------------------------------------------------------|---------------------------------| | Inclusion criteria | X | | Informed consent | X | | Patient demography (age, date of birth, gende...
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NCT03784898
3
LIST OF ABBREVIATIONS
3 LIST OF ABBREVIATIONS ADL: activity of daily living AE: adverse event ALT: alanine aminotransferase BMI: body mass index CNS: central nervous system CRF: case report form CTCAE: Common Terminology Criteria for Adverse Events eCRF: electronic case report form GCP: Good Clinical Practice ICF: informed consent form IMP:...
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NCT03784898
4
INTRODUCTION AND RATIONALE
4 INTRODUCTION AND RATIONALE
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NCT03784898
4.1
INTRODUCTION
4.1 INTRODUCTION Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that affects more than 2.3 million people worldwide [\(1\)](#page-38-1). Its clinical course is typically characterized by initial episodes of transient neurological compromise with full recovery, followed by a phase...
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NCT03784898
4.2
STUDY RATIONALE
4.2 STUDY RATIONALE In a previous analysis on a small number of patients from the Ph3 clinical trial population, a specific single nucleotide polymorphism (SNP) genetic set was identified showing a strong correlation with development of ITP after treatment by alemtuzumab (unpublished internal data). However samples fro...
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NCT03784898
5
STUDY OBJECTIVES
5 STUDY OBJECTIVES
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NCT03784898
5.1
PRIMARY OBJECTIVE
5.1 PRIMARY OBJECTIVE To collect blood samples, in a new cohort of RMS patients who have developed Immune thrombocytopenic purpura (ITP) after LEMTRADA treatment, for future DNA analysis as part of a global biomarker project assessing pre-identified candidate SNPs associated to the development of ITP after LEMTRADA tre...
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NCT03784898
5.2
EXPLORATORY OBJECTIVES:
5.2 EXPLORATORY OBJECTIVES: To collect from these patients additional serum, plasma, circulating PBMCs, and RNA samples together with their retrospective demographic and clinical data related to MS disease and ITP status
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NCT03784898
6
STUDY DESIGN
6 STUDY DESIGN
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NCT03784898
6.1
DESCRIPTION OF THE STUDY
6.1 DESCRIPTION OF THE STUDY This is a phase 4, single-center, non-randomized study conducted in one site in the USA; the study may be expanded to Canada at an undetermined number of sites. No investigational medicinal product (IMP) administration will be performed. Some retrospective demographic and clinical data will...
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NCT03784898
6.2
DURATION OF STUDY PARTICIPATION
6.2 DURATION OF STUDY PARTICIPATION
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NCT03784898
6.2.1
Duration of study participation for each patient
6.2.1 Duration of study participation for each patient This duration is from one to 70 days. Screening and visit(s) can be performed the same day or on separate days with a maximum timeframe of 30 days apart. One visit is required for blood draw. However, for safety reason and at the discretion of the medical team, the...
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NCT03784898
6.2.2
Determination of end of clinical trial (all patients)
6.2.2 Determination of end of clinical trial (all patients) The end of the clinical trial is defined as the day of last patient last visit.
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NCT03784898
6.3
INTERIM ANALYSIS
6.3 INTERIM ANALYSIS No interim analysis is planned.
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NCT03784898
7
SELECTION OF SUBJECTS
7 SELECTION OF SUBJECTS
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NCT03784898
7.1
NUMBER OF SUBJECTS PLANNED
7.1 NUMBER OF SUBJECTS PLANNED Approximately 35 patients
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NCT03784898
7.2
INCLUSION CRITERIA
7.2 INCLUSION CRITERIA - I 01. Male and female adult patients who have been treated with LEMTRADA, with development of ITP subsequent to treatment. Patients do not need to be currently on LEMTRADA treatment. - I 02. Patients who have signed the study informed consent form (ICF).
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NCT03784898
7.3
EXCLUSION CRITERIA
7.3 EXCLUSION CRITERIA None
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NCT03784898
8
STUDY TREATMENTS
8 STUDY TREATMENTS
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