Clinical Laboratory Parameters in Adolescents with Moderate-to-Severe Atopic Dermatitis Treated with Tralokinumab Up to Week 52 in the Phase 3 ECZTRA 6 Trial.

BackgroundAbrocitinib, an oral, once-daily, Janus kinase 1-selective inhibitor, is efficacious in moderate-to-severe atopic dermatitis with a manageable long-term safety profile.ObjectiveWe aimed to provide updated integrated long-term safety results for abrocitinib from available data accrued up to a maximum of almost 4 years in patients with moderate-to-severe atopic dermatitis from the JADE clinical development program.MethodsAnalysis included 3802 patients (exposure: 5213.9 patient-years) from the phase II monotherapy study (NCT02780167) and the phase III studies JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871), JADE TEEN (NCT03796676), JADE COMPARE (NCT03720470), JADE DARE (NCT04345367; 200 mg only), JADE REGIMEN (NCT03627767), and JADE EXTEND (NCT03422822; data cutoff 25 September, 2021). Data from patients receiving one or more doses of abrocitinib 200 mg or 100 mg were pooled in a consistent-dose cohort (patients were allocated to receive the same abrocitinib dose throughout exposure in the qualifying parent study and/or long-term study) or a variable-dose cohort (patients received open-label abrocitinib 200 mg; responders were randomized to abrocitinib 200 mg, 100 mg, or placebo, and could then receive abrocitinib 200 mg plus topical corticosteroids as rescue therapy). Incidence rates of adverse events of special interest were assessed. Cox regression analysis of risk factors for herpes zoster and serious infections was performed.ResultsOverall, this safety analysis of long-term data up to a maximum of ~ 4 years of abrocitinib exposure does not indicate any changes from the previously reported risk profile. The most frequent serious infections (per Medical Dictionary for Regulatory Activities preferred term) with consistent-dose abrocitinib 200 mg and 100 mg were herpes zoster (0.5% and 0.2%), pneumonia (0.2% with either dose), and herpes simplex (0.1% with either dose). Risk factors for herpes zoster were a history of herpes zoster, abrocitinib 200-mg dose, age ≥ 65 years, absolute lymphocyte count < 1 × 103/mm3 before the event, and residing in Asia. For serious infections, > 100 kg body weight was a risk factor. Incidence rate/100 patient-years (95% confidence interval) with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in older (aged ≥ 65 years) patients versus younger (aged 18 to < 65 years) patients for serious adverse events (17.6 [11.7‒25.4] vs 6.7 [5.8‒7.8]), malignancy excluding non-melanoma skin cancer (2.4 [0.6‒6.0] vs 0.1 [0.0‒0.4]), non-melanoma skin cancer (2.4 [0.6‒6.1] vs 0.2 [0.1‒0.4]), lymphopenia (3.5 [1.3‒7.6] vs 0.1 [0.0‒0.3]), and venous thromboembolism (1.7 [0.4‒5.1] vs 0.1 [0.0‒0.3]). Incident rate/100 patient-years (95% confidence interval) of non-melanoma skin cancer with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in current/former smokers (0.9 [0.4‒1.6]) vs never-smokers (0.0 [0.0‒0.1]).ConclusionsThis safety update showed a consistent profile for abrocitinib with no new safety signals and continues to support that abrocitinib has a manageable long-term safety profile in patients with moderate-to-severe atopic dermatitis. Risk of specific adverse events was higher in certain patient populations, especially those aged ≥ 65 years. [Video abstract available.]Clinical Trial RegistrationNCT02780167; study start date: April, 2016; primary completion date: March, 2017; study completion date: April, 2017. NCT03349060; study start date: 7 December, 2017; study completion date: 26 March, 2019. NCT03575871; study start date: 29 June, 2018; study completion date: 13 August, 2019. NCT03720470; study start date: 29 October, 2018; primary completion date: 27 December, 2019; study completion date: 6 March, 2020. NCT03796676; study start date: 18 February, 2019; study completion date: 8 April, 2020. NCT03627767; study start date: 11 June, 2018; primary completion date: 2 September, 2020; study completion date: 7 October, 2020. NCT04345367; study start date: 11 June, 2020; primary completion date: 16 December, 2020; study completion date: 13 July, 2021. NCT03422822; study start date: 8 March, 2018; study completion date: ongoing (estimated completion date: 31 January, 2026).Supplementary InformationThe online version contains supplementary material available at 10.1007/s40257-024-00869-w.

Background and ObjectiveThere is a need for long-term atopic dermatitis (AD) treatments that can effectively improve AD involvement of the head and neck (H&N) region (referred to as H&N AD). Tralokinumab, a high-affinity monoclonal antibody that neutralizes interleukin-13, is approved for the treatment of moderate-to-severe AD. Recent real-world studies have observed the effectiveness of tralokinumab for H&N AD. Here, data from phase III parent trials, ECZTRA 1 and ECZTRA 2, and the long-term extension trial, ECZTEND, were used to assess impacts of long-term tralokinumab treatment on H&N AD and the association between improvements in H&N AD and patient quality of life, and to evaluate whether a proportion of patients developed paradoxical H&N erythema.MethodsThese post hoc analyses included data from all patients initiated on tralokinumab in ECZTRA 1 or ECZTRA 2. Patients were treated up to 4 years (i.e., up to 52 weeks in ECZTRA 1 or ECZTRA 2 plus up to 152 weeks in ECZTEND). Outcomes included body region subscores of the Eczema Area and Severity Index (EASI; H&N, upper limbs, trunk, lower limbs) and the Dermatology Life Quality Index (DLQI). Correlations between H&N EASI and DLQI were assessed with Spearman’s correlation coefficient (ρ). The incidence of paradoxical H&N erythema (defined as H&N EASI erythema increasing from baseline to a score of 3, while all other regional EASI subscores are 0 or 1, during two or more consecutive visits) was also assessed.ResultsOverall, 1192 patients who were initiated on tralokinumab in ECZTRA 1 and ECZTRA 2, of whom 523 patients opted to continue in ECZTEND, were analyzed. Percentages of patients who had H&N EASI ≤ 1 increased from 12.2% at parent trial baseline to 87.2% by week 152 of ECZTEND. Improvements in EASI subscore outcomes from parent trial baseline were comparable across body regions throughout all timepoints of the study. At parent trial week 16, H&N EASI was moderately correlated with total DLQI (ρ = 0.47), with the strongest numerical correlations observed for DLQI questions regarding skin discomfort (ρ = 0.43) and embarrassment due to skin (ρ = 0.40). During up to 4 years of treatment, seven tralokinumab-treated patients exhibited paradoxical H&N erythema, five of whom improved to absent or mild H&N EASI erythema with continued tralokinumab treatment.ConclusionsTralokinumab provided progressive and sustained improvements in H&N AD, with H&N EASI 0/1 observed in nearly 90% of patients treated up to 4 years. Improvements in H&N EASI were similar to improvements observed for other body regions and were associated with improvements in patient quality of life, particularly for skin discomfort and self-consciousness/embarrassment due to skin.Clinical Trial RegistrationNCT03131648 (ECZTRA 1); study start date: 30 May, 2017; primary completion date: 7 August, 2018; study completion date: 10 October, 2019. NCT03160885 (ECZTRA 2); study start date: 12 June, 2017; primary completion date: 4 September, 2019; study completion date: 14 August, 2019. NCT03587805 (ECZTEND); study start date: 18 March, 2018; data cut-off date: 30 April, 2022; primary completion date: 3 July, 2024; study completion date: 3 July, 2024.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1007/s40257-025-00931-1.

Atopic dermatitis

Investigator's Global Assessment of clear/almost clear skin (IGA 0/1) is a difficult endpoint to achieve after short-term treatment of chronic moderate-to-severe atopic dermatitis, and does not fully reflect clinically meaningful changes in other parameters. We assessed the impact of tralokinumab versus placebo on other clinically meaningful parameters in patients not achieving IGA 0/1 at week 16 using pooled data from two monotherapy phase III trials, ECZTRA 1 and 2. This post hoc analysis included patients (n = 1328) from ECZTRA 1 and 2 who did not achieve the co-primary endpoint, IGA 0/1 at week 16 without rescue medication. Endpoints evaluating atopic dermatitis extent and severity included proportions of patients achieving IGA 0/1, 50%, 75%, and 90% improvement in Eczema Area and Severity Index (EASI-50/75/90); endpoints evaluating patient-reported outcomes included a ≥3-point improvement in worst daily pruritus Numerical Rating Scale (NRS), a ≥3-point improvement in eczema-related sleep interference (sleep) NRS, a ≥4-point improvement in Dermatology Life Quality Index (DLQI), and DLQI ≤5. Specifically, clinically meaningful responses were defined as EASI-50, a ≥3-point improvement in itch NRS, or a ≥ 4-point improvement in DLQI at week 16. Among ECZTRA 1 and 2 patients who did not achieve IGA 0/1 at week 16 without rescue medication, a significantly greater proportion of patients receiving tralokinumab versus placebo achieved EASI-50 (33.0% vs 13.0%), a ≥ 3-point improvement in itch NRS (22.6% vs 9.4%), or a ≥4-point improvement in DLQI (41.2% vs 24.5%) at week 16. In addition, compared with placebo, a numerically greater proportion of tralokinumab-treated patients achieved all three measures of clinically meaningful response (30% vs 18%) or a clinically meaningful change in at least one outcome (48.8% vs 28.5%). Significantly greater proportions of patients receiving tralokinumab versus placebo achieved additional clinician-reported and patient-reported outcomes, such as EASI-75 (13.5% vs 4.1%), EASI-90 (3.5% vs 1.1%), DLQI ≤5 (22.5% vs 12.5%), and a ≥3-point improvement in sleep NRS (24.5% vs 11.5%). Tralokinumab provided clinically meaningful responses in patients with moderate-to-severe atopic dermatitis who did not achieve IGA 0/1 at week 16 and/or used rescue medication. Using multiple validated outcome measures of both efficacy and quality of life, alongside IGA scores, can better characterize tralokinumab treatment responses in patients with moderate-to-severe atopic dermatitis. [Video abstract available] CLINICAL TRIAL REGISTRATION: NCT03131648 (ECZTRA 1); study start date: 30 May, 2017; primary completion date: 7 August, 2018; study completion date: 10 October, 2019. NCT03160885 (ECZTRA 2); study start date: 12 June, 2017; primary completion date: 4 September, 2019; study completion date: 14 August, 2019. Video abstract: Tralokinumab provides clinically meaningful responses at week 16 in adults with moderate-to-severe atopic dermatitis who do not achieve IGA 0/1 (MP4 362818 KB).

Two phase III trials, ECZTRA 1 and 2, confirmed the efficacy and safety of tralokinumab versus placebo in adults with moderate-to-severe atopic dermatitis (AD). To further explore the long-term efficacy of tralokinumab for AD, a pooled analysis of these trials was conducted. ECZTRA 1 and 2 patients (n = 1596 total) were randomized to tralokinumab 300mg or placebo every 2weeks (q2w) over 16weeks. Patients achieving Investigator's Global Assessment of clear/almost clear skin (IGA 0/1) and/or 75% improvement in the Eczema Area and Severity Index (EASI-75) at Week 16, were re-randomized to tralokinumab q2w, every 4weeks (q4w), or placebo (tralokinumab withdrawal) for another 36weeks. Patients not achieving the response criteria at Week 16 received open-label tralokinumab q2w plus optional topical corticosteroids (TCS). A pooled, prespecified analysis assessed the proportions of Week 16 responders that maintained IGA 0/1 and/or EASI-75 at Week 52. Pooled data from all patients initiated with tralokinumab, regardless of the response at Week 16 or dosing regimen received thereafter, were analyzed post hoc. In patients who achieved the primary endpoints at Week 16, IGA 0/1 responses were maintained at Week 52 without rescue treatment (including TCS) by 55.9%, 42.4%, and 34.0% of patients re-randomized to tralokinumab q2w, q4w, or placebo (tralokinumab withdrawal), respectively, while EASI-75 responses were maintained by 57.3%, 50.4%, and 26.4%, respectively (prespecified analysis). In a post hoc analysis of all patients initiated with tralokinumab, response rates improved over time with continued tralokinumab treatment beyond Week 16 to Week 52 for EASI-50 (63.1-82.7%), EASI-75 (37.6-61.8%), EASI-90 (20.4-37.3%), and IGA 0/1 (23.0-36.2%). Tralokinumab treatment provides progressive and sustained improvement over 1 year in the extent and severity of AD in patients with moderate-to-severe AD. NCT03131648 (ECZTRA 1); study start date: 30 May 2017; primary completion date: 7 August 2018; study completion date: 10 October 2019. NCT03160885 (ECZTRA 2); study start date: 12 June 2017; primary completion date: 4 September 2019; study completion date: 14 August 2019. INFOGRAPHIC.

Atopic Dermatitis in Latin America: A Roadmap to Address Data Collection, Knowledge Gaps, and Challenges.

BackgroundLaboratory testing is typically required for patients with atopic dermatitis (AD) treated with systemic immunosuppressants. A previous analysis of laboratory outcomes in randomized, double-blinded, placebo-controlled clinical trials of dupilumab in adults with moderate-to-severe AD found no clinically important changes in hematologic, serum chemistry, and urinalysis parameters, supporting the use of dupilumab without routine laboratory monitoring.ObjectiveThe aim was to assess laboratory results in adolescents with moderate-to-severe AD treated with dupilumab in a phase 3, randomized, double-blind, placebo-controlled trial.MethodsAdolescents aged ≥ 12 to < 18 years with moderate-to-severe AD were randomized 1:1:1 to subcutaneous dupilumab 200/300 mg every 2 weeks (q2w) (200 mg for patients < 60 kg at baseline; 300 mg for patients ≥ 60 kg at baseline); dupilumab 300 mg every 4 weeks (q4w); or placebo for 16 weeks. Laboratory evaluations included hematology, serum chemistry, and urinalysis parameters.ResultsOf 251 patients enrolled in the study, 250 received treatment and were included in the analysis. 4.7%, 2.4%, and 4.8% of patients receiving placebo, dupilumab 200/300 mg q2w, and dupilumab 300 mg q4w, respectively, had laboratory abnormalities reported as treatment-emergent adverse events, none of which prompted discontinuation of study treatment or study withdrawal. Mean eosinophil counts were elevated at baseline in all treatment groups. Patients in both dupilumab regimens, but not the placebo group, showed mild transient increases in mean eosinophil counts above baseline that returned to near-baseline values by week 16. Mean levels of lactate dehydrogenase trended towards the upper limit of normal at baseline and decreased with treatment; greater decreases were seen in dupilumab-treated patients than placebo-treated patients. There were no meaningful changes in other laboratory parameters, and none of the laboratory abnormalities were clinically significant.ConclusionNo clinically meaningful changes in laboratory parameters were seen in adolescents, similar to that observed in adults. The findings of this study indicate no routine laboratory monitoring is required in this population prior to or during dupilumab treatment.Trial RegistrationClinicalTrials.gov: NCT03054428.Video Video abstract: Effect of Dupilumab on Laboratory Parameters in Adolescents with Atopic Dermatitis: Results from a Randomized Placebo-Controlled Phase 3 Clinical Trial (MP4 175137 KB)Supplementary InformationThe online version contains supplementary material available at 10.1007/s40257-020-00583-3.

Delgocitinib cream is a topical pan-Janus kinase inhibitor approved for adults with moderate to severe Chronic Hand Eczema (CHE) in the USA, Canada, European Union, and multiple other countries. Here, we assessed the systemic exposure of twice-daily topical application of delgocitinib cream 20 mg/g in adults with moderate to severe CHE treated under normal or maximal use conditions in the DELTA 2 trial and compared with the systemic exposure in adults with moderate to severe atopic dermatitis (AD) from a delgocitinib cream phase 1 AD trial. Blood sampling was performed 2-6h after delgocitinib cream application at weeks 1, 4, and 16 in DELTA 2. In the delgocitinib cream phase 1 trial, blood sampling was performed prior to application and at six timepoints (0-12h) post-application on day 1 and day 8. Geometric mean delgocitinib plasma concentrations were calculated in DELTA 2 and peak delgocitinib plasma concentrations (geometric mean Cmax) were calculated in the phase 1 trial. In DELTA 2, patients treated with delgocitinib cream under normal (n = 294; body surface area [BSA], 1.48%; application, 7.3g/week) or maximal use conditions (n = 19; BSA, 2.17%; application, 13.7g/week) showed geometric mean delgocitinib plasma concentrations at week 1 of 0.19ng/mL (n = 268) and 0.58ng/mL, respectively. In the phase 1 trial, patients (n = 14; BSA, 33.6%; application, 72.3g/week) showed a geometric mean Cmax of 1.20ng/mL (n = 13) on day 8. Delgocitinib cream 20mg/g resulted in minimal systemic exposure among adults with moderate to severe CHE, including those treated under maximal use conditions. Low systemic exposure was also observed in adults with moderate to severe AD, despite substantially greater BSA involvement and higher delgocitinib cream usage, highlighting the properties of delgocitinib cream's novel formulation. NCT03826901 (phase 1, delgocitinib cream); study start date: 20 February 2019; primary completion date: 29 October 2021; study completion date: 29 October 2021. NCT04872101 (DELTA 2); study start date: 25 May 2021; primary completion date: 27 December 2022; study completion date: 6 January 2023.

BackgroundThe efficacy and safety of tralokinumab, a fully human monoclonal antibody that specifically neutralizes interleukin-13, plus topical corticosteroids (TCS) as needed were evaluated over 32 weeks in the phase III ECZTRA 3 trial. Significantly more tralokinumab- versus placebo-treated patients achieved the primary endpoints of Investigator’s Global Assessment (IGA) score of 0/1 and 75% improvement in Eczema Area and Severity Index (EASI-75) and all confirmatory endpoints at Week 16.ObjectiveThis post hoc analysis investigated the impact of tralokinumab plus TCS on atopic dermatitis (AD) severity, symptoms, and health-related quality of life (QoL) over the entire 32-week treatment period of ECZTRA 3, including all patients initiated on tralokinumab irrespective of the response achieved at Week 16.MethodsPatients were randomized 2:1 to receive subcutaneous tralokinumab 300 mg or placebo every 2 weeks (q2w) with TCS as needed for an initial 16 weeks. At Week 16, patients who achieved the clinical response criteria (IGA 0/1 and/or EASI-75) with tralokinumab were re-randomized 1:1 to tralokinumab q2w or every 4 weeks (q4w), with TCS as needed, for another 16 weeks. Patients not achieving the clinical response criteria with tralokinumab received tralokinumab q2w plus TCS from Week 16. All patients randomized to tralokinumab in the initial treatment period were pooled for this analysis, irrespective of response at Week 16 or dosing regimen beyond Week 16.ResultsContinued tralokinumab (q2w, N = 164; q4w, N = 69) plus TCS treatment provided progressive improvements from Week 16 onwards in AD signs, with 70.2% (177/252) of patients achieving EASI-75 and 50.4% (127/252) achieving EASI-90 at Week 32. Improvements in patient-reported outcomes were observed within the first few weeks of tralokinumab q2w plus TCS treatment and were sustained throughout the 32-week period. At Week 32, patients initiated on tralokinumab q2w plus TCS achieved a relative improvement versus baseline of 70.8% (standard error (SE), 2.4) in eczema-related sleep interference numeric rating scale (NRS) and 66.8% (SE, 3.1) in Dermatology Life Quality Index (DLQI). Mean TCS use during Weeks 16–32 ranged from 9.2 to 13.6 g (SE, 1.2–2.0) q2w. Most patients (89.9% (222/247)) initiated on tralokinumab q2w plus TCS achieved a meaningful improvement in at least one of the three disease domains, including AD signs (EASI-50), symptoms (pruritus NRS improvement ≥ 3), and QoL (DLQI improvement ≥ 4) at Week 16. Of patients initiated on tralokinumab q2w plus TCS, 53.4% (132/247) achieved a clinically meaningful improvement in all three domains at Week 16 (vs. placebo, 28.5% (35/123); p < 0.001).ConclusionsContinued tralokinumab treatment plus TCS as needed provides progressive and sustained improvements in AD signs, symptoms, and health-related QoL over 32 weeks.Clinical trial registrationNCT03363854; study start date: 22 February 2018; primary completion date: 8 March 2019; study completion date: 26 September 2019.InfographicVideo abstract: What is the impact of tralokinumab plus topical corticosteroids in adults with moderate-to-severe atopic dermatitis over 32 weeks? (MP4 216,988 KB)Supplementary InformationThe online version contains supplementary material available at 10.1007/s40257-022-00702-2.

Background: An important principle in the good conduct of clinical trials is that a summary of the trial protocol, with a pre-defined primary outcome, should be freely available before the study commences. The clinical trials registry ClinicalTrials.gov provides one method of doing this, and once the trial is registered, any changes made to the primary outcome are documented. The objectives of this study were: to assess the proportion of registered trials on ClinicalTrials.gov that had the primary outcome changed; to assess when the primary outcome was changed in relation to the listed study start and end dates and to assess whether the primary outcome change had any relation to the study sponsor. Methods: A cross-sectional analysis of all interventional clinical trials registered on ClinicalTrials.gov as of 25 October 2012 was performed. The main outcome was any change made to the initially listed primary outcome and the time of the change in relation to the trial start and end date. Findings: Our analysis showed that 28229 of 89204 (31.7%) registered studies had their primary outcome changed. Industry funding was associated with all primary outcome changes, odds ratio (OR)= 1.36, 95% confidence interval (CI)=1.31-1.41, p<0.001; with primary outcome changes after study start date OR=1.37, 95% CI=1.32-1.42, p<0.001; with primary outcome changes after primary completion date OR=1.84, 95% CI=1.75-1.94, p<0.001 and with primary outcome changes after study completion date OR=1.82, 95% CI=1.73-1.91, p<0.001. Conclusions A significant proportion of interventional trials registered on ClinicalTrials.gov have their primary outcomes altered after the listed study start and completion dates. These changes are associated with funding source.

An important principle in the good conduct of clinical trials is that a summary of the trial protocol, with a pre-defined primary outcome, should be freely available before the study commences. The clinical trials registry ClinicalTrials.gov provides one method of doing this, and once the trial is registered, any changes made to the primary outcome are documented. The objectives of this study were: to assess the proportion of registered trials on ClinicalTrials.gov that had the primary outcome changed; to assess when the primary outcome was changed in relation to the listed study start and end dates and to assess whether the primary outcome change had any relation to the study sponsor. A cross-sectional analysis of all interventional clinical trials registered on ClinicalTrials.gov as of 25 October 2012 was performed. The main outcome was any change made to the initially listed primary outcome and the time of the change in relation to the trial start and end date. Our analysis showed that 28229 of 89204 (31.7%)registered studies had their primary outcome changed. Industry funding was associated with all primary outcome changes, odds ratio (OR)= 1.36, 95% confidence interval (CI)=1.31-1.41, p<0.001; with primary outcome changes after study start date OR=1.37, 95% CI=1.32-1.42, p<0.001; with primary outcome changes after primary completion date OR=1.84, 95% CI=1.75-1.94, p<0.001 and with primary outcome changes after study completion date OR=1.82, 95% CI=1.73-1.91, p<0.001. Conclusions A significant proportion of interventional trials registered on ClinicalTrials.gov have their primary outcomes altered after the listed study start and completion dates. These changes are associated with funding source.

Background : An important principle in the good conduct of clinical trials is that a summary of the trial protocol, with a pre-defined primary outcome, should be freely available before the study commences. The clinical trials registry ClinicalTrials.gov provides one method of doing this, and once the trial is registered, any changes made to the primary outcome are documented. The objectives of this study were: to assess the proportion of registered trials on ClinicalTrials.gov that had the primary outcome changed; to assess when the primary outcome was changed in relation to the listed study start and end dates and to assess whether the primary outcome change had any relation to the study sponsor. Methods : A cross-sectional analysis of all interventional clinical trials registered on ClinicalTrials.gov as of 25 October 2012 was performed. The main outcome was any change made to the initially listed primary outcome and the time of the change in relation to the trial start and end date. Findings : Our analysis showed that 28229 of 89204 (31.7%)&nbsp;registered studies had their primary outcome changed. &nbsp;Industry funding was associated with all primary outcome changes, odds ratio (OR)= 1.36, 95% confidence interval (CI)=1.31-1.41, p&lt;0.001; with primary outcome changes after study start date OR=1.37, 95% CI=1.32-1.42, p&lt;0.001; with primary outcome changes after primary completion date OR=1.84, 95% CI=1.75-1.94, p&lt;0.001 and with primary outcome changes after study completion date OR=1.82, 95% CI=1.73-1.91, p&lt;0.001.&nbsp; Conclusions A significant proportion of interventional trials registered on ClinicalTrials.gov have their primary outcomes altered after the listed study start and completion dates. These changes are associated with funding source.

Introduction/Background Tralokinumab, a high-affinity, monoclonal antibody that targets IL-13, is approved in the EU and Canada for adolescents (aged ≥12 years) with inadequately controlled moderate-to-severe atopic dermatitis (AD), and it does not require laboratory monitoring. The phase 3 ECZTRA 6 (NCT03526861) clinical trial demonstrated efficacy and safety up to 52 weeks in that population. Objectives To further characterize the safety profile of tralokinumab by evaluating laboratory parameters of adolescents in the ECZTRA 6 trial. Methods ECZTRA 6 subjects received tralokinumab 150mg (n=98), 300mg (n=97) or placebo (n=94) every 2 weeks (Q2W) from week 0–16 after a loading dose at week 0 (twice the subsequent dose), and then randomized to maintenance [original tralokinumab dose either Q2W or every 4 weeks (Q4W) or placebo Q2W] or open-label (tralokinumab 300mg Q2W) until week 52. Laboratory parameters included hematology, serum biochemistry, and urinalysis throughout the trial (weeks 0, 8, 16, 28, and 52). Results Overall (n= 289 subjects), laboratory baseline parameters were similar across treatment groups. Mean and median changes of most hematology parameters showed minor fluctuations within the normal ranges through week 52, except for eosinophils. At baseline, elevated mean eosinophil counts (&amp;gt;0.5 109/L) were observed for 40.8% (tralokinumab 150mg), 48.5% (tralokinumab 300mg), and 43.6% (placebo) of subjects in each respective treatment group. Some tralokinumab-treated patients had small transient increases in eosinophils (maximum mean change from baseline 0.2×109/L) before week 16. Continued treatment with tralokinumab or placebo did not correspond with further increase in eosinophil levels over time, and no adverse events of eosinophilia were reported. Mean levels of most biochemistry parameters, including electrolytes, renal and liver function parameters, and lipid panel, were within normal range at baseline, and mean and median changes showed minor fluctuations within normal ranges in all treatment arms. Mean lactate dehydrogenase levels were around or above the upper limit of normal at baseline and decreased to within the normal ranges during the trial across all groups. Overall, no clinically meaningful differences were observed in hematology, biochemistry, or urinalysis parameters between active treatment groups or placebo. Conclusions Similar to findings in adult trials, no meaningful changes in laboratory parameters were observed in adolescents through week 52 with tralokinumab treatment. No routine laboratory monitoring is needed for adult or adolescent AD patients treated with tralokinumab.

Introduction: Tralokinumab, a high-affinity, monoclonal antibody that targets IL-13, is approved in the EU and Canada for adolescents (aged ≥12 years) with inadequately controlled moderate-to-severe atopic dermatitis (AD), and it does not require laboratory monitoring. The phase 3 ECZTRA 6 (NCT03526861) clinical trial demonstrated efficacy and safety up to 52 weeks in that population.&#x0D; Objective/Purpose: To further characterize the safety profile of tralokinumab by evaluating laboratory parameters of adolescents in the ECZTRA 6 trial.&#x0D; Methods: ECZTRA 6 subjects received tralokinumab 150mg (n=98), 300mg (n=97) or placebo (n=94) every 2 weeks (Q2W) from week 0–16 after a loading dose at week 0 (twice the subsequent dose), and then randomized to maintenance [original tralokinumab dose either Q2W or every 4 weeks (Q4W) or placebo Q2W] or open-label (tralokinumab 300mg Q2W) until week 52. Laboratory parameters included hematology, serum biochemistry, and urinalysis throughout the trial (weeks 0, 8, 16, 28, and 52).&#x0D; Results: Overall (n= 289 subjects), laboratory baseline parameters were similar across treatment groups. Mean and median changes of most hematology parameters showed minor fluctuations within the normal ranges through week 52, except for eosinophils. At baseline, elevated mean eosinophil counts (&gt;0.5 109/L) were observed for 40.8% (tralokinumab 150mg), 48.5% (tralokinumab 300mg), and 43.6% (placebo) of subjects in each respective treatment group. Some tralokinumab-treated patients had small transient increases in eosinophils (maximum mean change from baseline 0.2×109/L) before week 16. Continued treatment with tralokinumab or placebo did not correspond with further increase in eosinophil levels over time, and no adverse events of eosinophilia were reported. Mean levels of most biochemistry parameters, including electrolytes, renal and liver function parameters, and lipid panel, were within normal range at baseline, and mean and median changes showed minor fluctuations within normal ranges in all treatment arms. Mean lactate dehydrogenase levels were around or above the upper limit of normal at baseline and decreased to within the normal ranges during the trial across all groups. Overall, no clinically meaningful differences were observed in hematology, biochemistry, or urinalysis parameters between active treatment groups or placebo.&#x0D; Conclusions: Similar to findings in adult trials, no meaningful changes in laboratory parameters were observed in adolescents through week 52 with tralokinumab treatment. No routine laboratory monitoring is needed for adult or adolescent AD patients treated with tralokinumab.

Investigator's Global Assessment (IGA) of clear/almost clear (0/1) skin is a high standard to achieve after 16 weeks of treatment for patients with moderate-to-severe atopic dermatitis (AD) and does not capture clinically meaningful responses in other patient domains, such as improvement in itch and/or quality of life. To better evaluate the effect of tralokinumab in adolescents, we assessed the clinically meaningful impact of tralokinumab versus placebo in patients who did not meet IGA 0/1 at week 16 without rescue medication in ECZTRA 6. These post hoc analyses included adolescents from the ECZTRA 6 (NCT03526861) phase 3 trial who did not achieve IGA 0/1 at week 16 without rescue medication (referred to as IGA >1). Clinically meaningful responses were defined as either ≥50% improvement from baseline in Eczema Area and Severity Index (EASI-50), ≥3-point improvement in Adolescent Worst Pruritus Numeric Rating Scale (itch NRS), or ≥6-point improvement in Children's Dermatology Life Quality Index (CDLQI) at week 16. Among IGA >1 patients (n = 247), significantly greater percentages receiving tralokinumab (150 mg or 300 mg) versus placebo achieved EASI-50 (31.2% or 41.3% versus 10.0%), ≥3-point improvement in itch NRS (21.6% or 22.8% versus 8.0%), or ≥1 clinically meaningful measure (36.4% or 52.5% versus 21.1%) at week 16. The majority of IGA >1 patients who continued with open-label tralokinumab beyond week 16 achieved EASI-50 and ≥3-point improvement in itch NRS and about 40% met EASI-90 at week 52. Clinically meaningful responses in both clinician-measured and patient-reported outcomes were observed in tralokinumab-treated (150 mg or 300 mg) adolescents who did not achieve IGA 0/1 at week 16 without rescue medication. Utilizing validated outcome measures of both efficacy and patient quality of life, alongside IGA scores, can enhance clinical decision-making regarding tralokinumab treatment responses in adolescents with moderate-to-severe AD. ClinicalTrials.gov identifier, NCT03526861 (ECZTRA 6); study start date: 19 June 2018; primary completion date: 15 April 2020; study completion date: 16 March 2021. A Graphical Abstract is available for this article.