PowerPoint Presentation Conjunctivitis in adolescent patients aged 12–17 with moderate-to-severe atopic dermatitis treated with tralokinumab up to week 52: results from the phase 3 ECZTRA 6 trial Andreas Wollenberg1,2, Marjolein de Bruin-Weller3, Jacob P. Thyssen4, Lisa A. Beck5, Eric L. Simpson6, Shinichi Imafuku7, Mark Boguniewicz8, Azra Kurbasic9, Lise Soldbro9, Natacha Strange Vest9, Petra Arlert9, Amy S. Paller10 1Ludwig Maximilian University of Munich, Department of Dermatology and Allergy, Munich, Germany; 2Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Department of Dermatology, Brussels, Belgium; 3Department of Dermatology and Allergology, University Medical Center Utrecht, Utrecht, Netherlands; 4Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark; 5Department of Dermatology, Medicine and Pathology, University of Rochester Medical Center, Rochester, NY, USA; 6Oregon Health & Science University, Portland, OR, USA; 7Fukuoka University, Fukuoka, Japan; 8Division of Allergy-Immunology, Department of Pediatrics, National Jewish Health, Denver, CO, USA; 9LEO Pharma, A/S, Ballerup, Denmark; 10Feinberg School of Medicine, Northwestern University, Chicago IL, USA Objective • To examine conjunctivitis frequency and severity in tralokinumab-treated adolescents with moderate-to-severe atopic dermatitis Patient characteristics • Baseline demographic and clinical characteristics were comparable across treatment groups (Table 1) Results • Conjunctivitis frequency in adolescents was low and similar between the tralokinumab and placebo arms of the phase 3 ECZTRA 6 trial • Conjunctivitis rates were numerically lower in adolescents compared with reported adult rates4, through Week 16 of the trial • The majority of conjunctivitis events were mild, and most resolved during Weeks 0–16; none led to permanent discontinuation of tralokinumab • The frequency and severity of conjunctivitis did not increase with longer-term tralokinumab treatment up to Week 52 Conclusions Introduction • Atopic dermatitis (AD) is a chronic inflammatory skin disease with limited safe and effective treatments suitable for long-term use in adolescents with moderate-to-severe disease1,2 • Various forms of conjunctivitis are commonly present in adult patients with AD,3 and can increase with biological treatments targeting the type 2 inflammatory pathway4,5 • Higher frequency of conjunctivitis was observed with dupilumab (which targets interleukin-4 and -13) vs placebo in an adolescent AD trial2 • Tralokinumab is a fully human monoclonal antibody that binds with high affinity to interleukin-13, a key driver of AD pathogenesis6–8 • Here, we examine the frequency and rate of conjunctivitis in adolescents treated with tralokinumab vs placebo in the phase 3 ECZTRA 6 trial Tralokinumab 300 mg Q2W Placebo Q2W Tralokinumab 300 mg Q2W Tralokinumab 300 mg Q4W Alternating with placebo Placebo Q2W Tralokinumab 300 mg Q2W Optional TCS and optional home use Initial treatmentScreening Maintenance treatment Patients with clinical response IGA 0/1 or EASI-75 Clinical response must be achieved without rescue Safety follow-up Open-label treatment 1:1:1 randomization Patients who: • Did not achieve IGA 0/1 or EASI-75 at Week 16 • Received rescue treatment between Week 2–16 • Were transferred from maintenance treatment if specific criteria were met Washout of TCS and other AD medication Initial loading dose 1:1 randomization 16 weeks0–6 weeks 52 weeks 66 weeks 1:1 randomization Tralokinumab 150 mg Q2W Tralokinumab 150 mg Q2W Tralokinumab 150 mg Q4W Alternating with placebo n=294 Figure 1. ECZTRA 6 trial design Rescue treatment during initial and maintenance treatment defined as: TCI, TCS or systemic AD treatment. AD, atopic dermatitis; EASI, Eczema Area and Severity Index; IGA, Investigator’s Global Assessment; Q2W, every 2 weeks; Q4W, every 4 weeks; TCS, topical corticosteroids. †Patients not achieving EASI-75 over ≥4 weeks with IGA ≥2 after IGA=0 at Week 16, or with IGA ≥3 after IGA=1 at Week 16, or who had IGA >1 at Week 16; patients who receive rescue treatment after Week 16 Patients Placebo (n=94) Tralokinumab 150 mg Q2W (n=98) Tralokinumab 300 mg Q2W (n=97) Mean age, years 14.3 14.8 14.6 Age group, n (%) 12–14 15–17 49 (52.1) 45 (47.9) 37 (37.8) 61 (62.2) 45 (46.4) 52 (53.6) Male sex, n (%) 51 (54.3) 51 (52.0) 47 (48.5) Mean duration of AD, years (SD) 12.1 (3.5) 12.7 (3.7) 12.1 (3.7) Severe disease (IGA=4), n (%) 43 (45.7) 44 (44.9) 48 (49.5) Mean EASI (SD) 31.2 (14.5) 32.1 (12.9) 31.8 (13.9) Mean SCORAD (SD) 67.4 (14.9) 67.7 (14.4) 68.3 (13.7) Mean CDLQI (SD) 13.3 (6.0) 12.9 (6.3) 13.4 (7.3) Mean Weekly Average Peak Pruritus NRS (SD) 7.5 (1.7) 7.5 (1.6) 7.8 (1.5) AD, Atopic Dermatitis; CDLQI, Children's Dermatology Life Quality Index; EASI, Eczema Area and Severity Index; IGA, Investigator's Global Assessment; n, Number of subjects in analysis set; NRS, Numeric rating scale; Q2W, Every 2 weeks; SCORAD, Scoring Atopic Dermatitis; SD, standard deviation. Frequency & Severity of Conjunctivitis: Weeks 0–16 • By Week 16, 2 patients (2.1%; rate 10.7) in the placebo arm had conjunctivitis (AESI) vs 4 patients (4.1%; rate 13.6) in the tralokinumab 150 mg arm and 3 patients (3.1%; rate 10.2) in the 300 mg arm (Table 3) • Only two conjunctivitis AESIs were reported as the preferred term ‘conjunctivitis’, both in the tralokinumab 150 mg arm • Overall, 2/10 (20%) events were confirmed by an ophthalmologist • The majority of conjunctivitis AESIs were considered mild in severity; no severe events were reported (Table 3) References 1. Weidinger S, et al. Nat Rev Dis Primers. 2018;4:1; 2. Simpson EL, et al. JAMA Dermatol. 2020;156:44–56; 3. Thyssen JP, et al. J Am Acad Dermatol. 2017; 77: 280–86.e28; 4. Wollenberg A, et al. Br J Dermatol. 2022;186:453–65; 5. Akinlade B, et al. Br J Dermatol. 2019;181:459-73; 6. Bieber T. Allergy. 2020;75:54–62; 7. Tsoi LC, et al. J Invest Dermatol. 2019;139:1480–89; 8. Popovic B, et al. J Mol Biol. 2017;429:208–19 Disclosures Andreas Wollenberg has received grants, personal fees, or nonfinancial support from AbbVie, Aileens, Almirall, Beiersdorf, Bioderma, Chugai, Galapagos, Galderma, GSK, Hans Karrer, LEO Pharma, Lilly, L’Oreal, Maruho, MedImmune, Merck, Novartis, Pfizer, Pierre Fabre, Regeneron, Santen, and Sanofi-Aventis. Marjolein de Bruin-Weller has served as a consultant, advisory board member, and/or speaker for AbbVie, Almirall, Arena, Aslan, Galderma, Janssen, Leo Pharma, Pfizer, Regeneron, and Sanofi-Genzyme, and Eli Lilly and Company. Jacob P. Thyssen has attended advisory boards for Eli Lilly & Co., Almirall, Arena Pharmaceuticals, Pfizer, AbbVie, LEO Pharma, Regeneron and Sanofi-Genzyme, been an investigator for LEO Pharma, Sanofi-Genzyme, Eli Lilly & Co., AbbVie and Pfizer, and received speaker honorarium from LEO Pharma, Pfizer, Almirall, Abbvie, Eli Lilly & Co., Regeneron and Sanofi-Genzyme. Lisa A. Beck has been a consultant for Allakos, Arena Pharmaceuticals, DermTech, Evelo Biosciences, Galderma, Incyte, Janssen, LEO Pharma, Merck, Numab Therapeutics, Pfizer, Rapt Therapeutics, Regeneron, Ribon Therapeutics, Sanofi/Genzyme, Sanofi-Aventis, Stealth BioTherapeutics, Trevi Therapeutics, Union Therapeutics and Xencor. DMC Member: Novartis. Investigator for Abbvie, Astra-Zeneca, DermTech, Kiniksa, Pfizer, Regeneron, and Ribon Therapeutics. Eric L. Simpson is a consultant and investigator for Regeneron/Sanofi, Dermira, Menlo Pharmaceuticals, Lilly, Abbvie, Genentech, Medimmune, GSK, LEO Pharma, Celgene, and Pfizer. Shinichi Imafuku is a researcher, consultant, or speaker for Abbvie, Amgen, Celgene, DaiichiSankyo, Eisai, KyowaKirin, Lilly, Taihoyakuhinkogyo, TanabeMitsubishi, Tsumura, Torii, Maruho, Novartis, LEO Pharma, and Janssen. Mark Boguniewicz has been a clinical study investigator for Regeneron and Incyte and served as a scientific adviser or consultant for Pfizer, AbbVie, Eli Lilly, LEO Pharma, Janssen, Regeneron, and Sanofi Genzyme. Azra Kurbasic, Lise Soldbro, Natacha Strange Vest, and Petra Arlert are employees of LEO Pharma A/S. Amy S. Paller has served as an investigator for AbbVie, Anaptysbio, Incyte, Janssen, KrystalBio, LEO Pharma, Regeneron, and UCB, received honorarium for consultancy from AbbVie, Abeona, Almirall, Anaptysbio, Arena, Azitra, BiomX, Boehringer Ingelheim, Castle Biosciences, Catawba, Dermira, Exicure, Forté, Kamari, LEO Pharma, Lilly, LifeMax, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Seanergy, and UCB, and served on a Data Safety Monitory Board for AbbVie, Galderma, and Novan. Acknowledgements The ECZTRA 6 clinical trial was sponsored by LEO Pharma A/S (Ballerup, Denmark). This poster is an encore of a previous presentation at the 12th International Symposium on Atopic Dermatitis, 17 – 19 October 2022. Editorial support from Alphabet Health (New York, NY, USA) by Juliel Espinosa, PhD and Meredith Whitaker, PhD was funded by LEO Pharma (USA). Scan to download a copy of this poster Copies of this poster and its content, obtained through this QR code, are for personal use only and may not be reproduced without written permission from the authors Outcomes of Conjunctivitis: Weeks 0–16 • Most outcomes (8/9) were recovered or resolved during Weeks 0–16, and none led to permanent tralokinumab discontinuation (Table 4) AESI, adverse event of special interest; Q2W, once every 2 weeks. Incidence of Conjunctivitis: Weeks 16–52 • During Weeks 16–52, 3 patients (6%; rate 11.9) had conjunctivitis (AESI) in the maintenance treatment phase (pooled tralokinumab arms) as did 11 patients (4.7%; rate 9.3) in the open-label treatment phase (Table 5) • Of these patients, five had events that were reported as the preferred term ‘conjunctivitis’ • All conjunctivitis AESIs during Weeks 16–52 (maintenance and open-label phases) were mild or moderate in severity, with no severe events recorded (Table 5) • Conjunctivitis was classified as an adverse event of special interest (AESI) prior to trial initiation • This broad term comprised the following preferred terms: conjunctivitis, conjunctivitis allergic, conjunctivitis bacterial, and conjunctivitis viral • Results were based on the safety analysis set comprised of all patients randomized and exposed to investigational medicinal product, excluding 9 patients from two sites with Good Clinical Practice non- compliance (N=289) • Rates were calculated as: • Number of events per patient-years of exposure x 100 Statistical analyses and endpoints • Conjunctivitis frequency and rate were examined in adolescent patients aged 12–17 years with moderate-to-severe AD treated with tralokinumab for up to 52 weeks in the phase 3 ECZTRA 6 trial (NCT03526861) Table 4. Outcome of Conjunctivitis AESI (Weeks 0–16) Materials and Methods Study design • Adolescent patients were randomized 1:1:1 to subcutaneous tralokinumab 150 mg or 300 mg every 2 weeks (Q2W), or placebo for an initial treatment period of 16 weeks • Primary endpoints were Investigator’s Global Assessment (IGA) score 0/1 and ≥75% improvement from baseline in Eczema Area and Severity Index (EASI-75) at Week 16 • Patients achieving primary endpoints without rescue treatment were re-randomized to tralokinumab Q2W or every 4 weeks (Q4W), at their same initial tralokinumab dosage for 36 weeks of maintenance treatment as shown in Figure 1, while Placebo responders continue in the Placebo Q2W • Patients not achieving primary endpoints at Week 16, those receiving rescue treatment from Week 2 to Week 16, and those meeting other specific criteria† were transferred to open-label treatment of tralokinumab 300 mg Q2W plus optional mild-to-moderate strength topical corticosteroids (TCS) • Key secondary endpoints include change in SCORing AD (SCORAD) from baseline to Week 16, reduction of worst daily pruritus numeric rating scale (NRS) (weekly average) of at least 4 from baseline to Week 16, and change in Children's Dermatology Life Quality Index (CDLQI) score from baseline to Week 16 Placebo (n=94) PYE 27.9 Tralokinumab 150 mg Q2W (n=98) PYE 29.3 Tralokinumab 300 mg Q2W (n=97) PYE 29.5 AESI category Preferred term N (%) Events Rate N (%) Events Rate N (%) Events Rate Conjunctivitis Conjunctivitis Conjunctivitis bacterial Conjunctivitis allergic Conjunctivitis viral 2 (2.1) – – 2 (2.1) – 3 – – 3 – 10.7 – – 10.7 – 4 (4.1) 2 (2.0) – 2 (2.0) – 4 2 – 2 – 13.6 6.8 – 6.8 – 3 (3.1) – 1 (1.0) 2 (2.1) – 3 – 1 2 – 10.2 – 3.4 6.8 – Severity Mild Moderate Severe 2 (2.1) – – 3 – – 10.7 – – 3 (3.1) 1 (1.0) – 3 1 – 10.2 3.4 – 2 (2.1) 1 (1.0) – 2 1 – 6.8 3.4 – AESI, adverse event of special interest; PYE, patient years of exposure; Q2W, once every 2 weeks. Placebo (n=94) Tralokinumab 150 mg Q2W (n=98) Tralokinumab 300 mg Q2W (n=97) N (%) Rate N (%) Rate N (%) Rate Conjunctivitis AESI Drug related Action taken with drug Dose not changed Drug interrupted 2 (2.1) 1 (1.1) 2 (2.1) – 10.7 7.2 10.7 – 4 (4.1) 1 (1.0) 3 (3.1) 1 (1.0) 13.6 3.4 10.2 3.4 3 (3.1) 1 (1.0) 3 (3.1) – 10.2 3.4 10.2 – Outcome Fatal Not recovered/not resolved Recovering/resolving Recovered/resolved – – – 2 (2.1) – – – 10.7 – – – 4 (4.1) – – – 13.6 – – 1 (1.0) 2 (2.1) – – 3.4 6.8 Table 3. Frequency of Conjunctivitis AESI (Weeks 0–16) Overall Summary of AEs: Weeks 0-16 • Tralokinumab was well-tolerated and the majority of adverse events (AEs) in the tralokinumab and placebo arms were mild or moderate in severity (Table 2) • No patterns were seen in types of serious AEs and none led to any safety concerns (Table 2) • The majority of AEs had resolved within the initial 16-week period; only one AE led to treatment withdrawal and was not considered related to treatment* (Table 2) Table 2. ECZTRA 6 Safety Summary (Weeks 0-16) *Cerebrovascular accident, not considered related to treatment by the investigator or study sponsor; The patient had several risk factors for developing cerebrovascular accident. The event was not considered related to treatment with tralokinumab by either investigator or sponsor/LEO. The outcome was reported as recovered with sequelae. †Includes the preferred terms conjunctivitis, conjunctivitis bacterial, conjunctivitis allergic and conjunctivitis viral (no cases of conjunctivitis viral were observed) AE, adverse event; Q2W, Every 2 weeks. Table 1. Baseline characteristics Maintenance treatment Open-label treatment Tralokinumab pooled total 150/300 mg Q2/4W (n=50) PYE 25.3 Tralokinumab 300 mg Q2W plus optional TCS (n=234) PYE 151.1 AESI category Preferred term N (%) Events Rate N (%) Events Rate Conjunctivitis Conjunctivitis Conjunctivitis bacterial Conjunctivitis allergic Conjunctivitis viral 3 (6.0) 1 (2.0) – 2 (4.0) – 3 1 – 2 – 11.9 4.0 – 7.9 – 11 (4.7) 4 (1.7) 3 (1.3) 4 (1.7) – 14 6 4 4 – 9.3 4.0 2.7 2.7 – Severity Mild Moderate Severe 1 (2.0) 2 (4.0) – 1 2 – 3.95 7.90 – 9 (3.8) 3 (1.3) – 10 4 – 6.6 2.7 – AESI, adverse event of special interest; PYE, patient years of exposure; Q2W, once every 2 weeks; TCS, topical corticosteroid Table 5. Incidence of Conjunctivitis (Weeks 16–52) Placebo (n=94) Tralokinumab 150 mg Q2W (n=98) Tralokinumab 300 mg Q2W (n=97) Adverse events, n (%) 58 (61.7) 66 (67.3) 63 (64.9) Serious adverse events, n (%) 5 (5.3) 3 (3.1) 1 (1.0) Severity, n (%) Mild Moderate Severe 40 (42.6) 31 (33.0) 7 (7.4) 48 (49.0) 33 (33.7) 5 (5.1) 47 (48.5) 32 (33.0) 3 (3.1) Leading to withdrawal, n (%) 0 1 (1.0) 0 AEs of special interest, n (%) Eye disorders Conjunctivitis† Eczema herpeticum Skin infections requiring systemic treatment Injection site reactions 2 (2.1) 2 (2.1) 1 (1.1) 2 (2.1) 1 (1.1) 4 (4.1) 4 (4.1) 1 (1.0) 5 (5.1) 9 (9.2) 4 (4.1) 3 (3.1) 0 2 (2.1) 7 (7.2)