Efficacy and safety of tralokinumab monotherapy in adult patients with moderate-to-severe atopic dermatitis: Results from two 52- week Phase 3 trials (ECZTRA 1 and ECZTRA 2)

Authors retain copyright.

Background

• AD is a chronic, inflammatory skin disease¹
• Tralokinumab is a fully human monoclonal antibody designed to specifically neutralize IL-13, a key driver of the underlying inflammation in AD^2-6
• The ECZTRA 1 and ECZTRA 2 studies were identical, global, double-blind, randomized, placebo-controlled, 52-week trials of tralokinumab monotherapy in over 1500 patients with moderate-to-severe AD

AD, atopic dermatitis; IL, interleukin.
1. Silverberg JI et al. Ann Allergy Asthma Immunol 2018;121:340-347; 2. Bieber T. Allergy 2020;75:54-62; 3. Furue K et al. Immunology 2019; 158: 281-286; 4. Szegedi K et al. JEADV 2015;29:2136–2144; 5. Tsoi LC et al. J Invest Dermatol 2019;139:1480-1489; 6. Popovic B et al. J Mol Biol 2017; 429: 208–219

---

ECZTRA 1 and 2 trial design

Patients with moderate-to-severe AD who were candidates for systemic therapy

BSA, body surface area; DLQI, Dermatology Life Quality Index; EASI, Eczema Area and Severity Index; EASI-75, at least 75% reduction in EASI score; HRQoL, health-related quality of life; IGA, Investigator’s Global Assessment; NRS, Numeric Rating Scale; q2w, every 2 weeks; q4w, every 4 weeks; SCORAD, SCORing Atopic Dermatitis; TCS, topical corticosteroid

---

Rescue medications

• Patients who used topical or systemic rescue treatment were considered non-responders
• Patients using rescue treatment were allowed to enter maintenance or open-label treatment at week 16

---

Patients had a long duration of AD and over 50% had severe AD (IGA-4) at baseline

a. USA only in ECZTRA 1; USA and Canada in ECZTRA 2;
b. France, Germany, and Spain in ECZTRA 1; Italy, Poland, Russia, Denmark, and UK in ECZTRA 2;
c apan in ECZTRA 1 and Korea in ECZTRA 2

---

Significantly greater IGA-0/1 response rates observed with tralokinumab at week 16

Rescue medication was used by 35.8% and 22.8% of patients receiving tralokinumab and by 46.2% and 44.3% of patients receiving placebo in ECZTRA 1 and 2, respectively

**p<0.01 versus placebo;
***p<0.001 versus placebo.
a. Use of rescue medication considered as nonresponse and missing data imputed as nonresponse;
b. All data used as observed at week 16, regardless of rescue medication use, and missing data imputed as nonresponse.
NRI, nonresponder imputation

---

Significantly greater EASI-75 response rates observed with tralokinumab at week 16

Rescue medication was used by 35.8% and 22.8% of patients receiving tralokinumab and by 46.2% and 44.3% of patients receiving placebo in ECZTRA 1 and 2, respectively

***p<0.001 versus placebo.
aUse of rescue medication considered as nonresponse and missing data imputed as nonresponse; bAll data used as observed at week 16,
regardless of rescue medication use, and missing data imputed as nonresponse.

---

Significantly more patients achieved improvement in worst daily pruritus NRS ≥4 at week 16

• Mean changes from baseline in SCORAD and DLQI were significantly improved with tralokinumab versus placebo at week 16
• Improvements in SCORAD and DLQI were observed from week 2 onward

Composite estimand (primary analysis): use of rescue medication considered nonresponse and missing data imputed as nonresponse.
*p<0.05 versus placebo; **p<0.01 versus placebo; ***p<0.001 versus placebo.
aBased on patients in the full analysis set with a baseline pruritus NRS (weekly average) ≥4.

---

Visible improvement in AD lesions within 16 weeks

---

Transfer to maintenance or open-label treatment after week 16

---

Patients with IGA 0/1 and EASI 75 at Week 16 and 52 without any TCS use^§

ECZTRA 1&2: Pooled data; Maintenance treatment period; Initial treatment: tralokinumab Q2W

§ Analysis of patients who achieved a clinical response (IGA 0/1 or EASI 75) with tralokinumab Q2W at Week 16 and were re-randomized to receive either tralokinumab Q2W, tralokinumab Q4W, or placebo until Week 52. Patients who received rescue medication or were transferred to open-label treatment considered non-responders. Patients with missing data imputed as non-responders.
IGA, Investigator’s Global Assessment; EASI, Eczema Area and Severity Index; Q2W, every 2 weeks; Q4W, every 4 weeks.

---

Some patients not achieving IGA-0/1 or EASI-75 at week 16 improved with continued treatment

ECZTRA 1&2: Pooled data; Patients transferred to open-label tralokinumab Q2W + optional TCS

Data are pooled from ECZTRA 1 and 2 and include all patients, irrespective of use of TCS, TCI, and other AD treatments.
TCI, topical calcineurin inhibitors.

---

Overall frequency and severity of AEs over 16 weeks was comparable between tralokinumab and placebo

• 97% of conjunctivitis cases were mild to moderate and only one led to treatment discontinuation
• Overall, the safety profile at week 52 was comparable with the initial treatment period

a. AEs reported by system organ class and preferred term according to MedDRA 20.0 in the initial treatment period.
AE, adverse event.

---

Combination study: IGA 0/1 and EASI 75 response rates at week 16

ECZTRA 3: Initial treatment period; Treatment: Tralokinumab Q2W+TCS as needed

Composite estimand (primary analysis): patients who received rescue medication considered non-responders.
***p<0.001 versus placebo.
Patients with missing data imputed as non-responders. EASI, Eczema Area and Severity Index; IGA, Investigator’s Global Assessment;
Q2W, every 2 weeks; TCS, topical corticosteroid.

---

Combination study: Patients with maintained response at Week 32

ECZTRA 3: Continuation treatment period; Initial treatment: tralokinumab Q2W + TCS as needed

Analysis of patients who achieved a clinical response with tralokinumab Q2W + TCS at Week 16 and were rerandomized to receive either tralokinumab Q2W + TCS or tralokinumab Q4W + TCS until Week 32. EASI, Eczema Area and Severity Index; IGA, Investigator’s Global Assessment; Q2W, every 2 weeks; Q4W, every 4 weeks TCS, topical corticosteroid.

---

Conclusions

• Tralokinumab demonstrated superiority over placebo in all primary and secondary endpoints at week 16
• The majority of patients maintained response at week 52 with tralokinumab q2w (without use of TCS)
• After having achieved response, q4w dosing could be appropriate for some patients
• Continued treatment beyond 16 weeks resulted in additional patients achieving treatment success
• The overall frequency of AEs was comparable to placebo over 52 weeks
• Specifically targeting IL-13 with tralokinumab may represent a novel efficacious approach for long-term treatment of AD
• Increased responder rates were seen with tralokinumab+TCS as needed at week 16, with 9 out of 10 responders maintaining response at week 32

---

Ask questions to Eric L. SIMPSON:

[contact-form-7 id=”3756″ title=”Ask question LIVE”]

---

Conflict of interest :

Disclosures
Eric SIMSON reports receiving grants and personal fees from AbbVie, Lilly, LEO Pharma, Pfizer, Regeneron, and MedImmune; grants from Galderma, Kyowa Hakko Kirin, Merck, Novartis, Tioga, and Celgene; and personal fees from Boehringer Ingelheim, Dermira, Dermavant, Forte Bio, Incyte, Menlo Therapeutics, Ortho Dermatologics, Pierre Fabre Dermo Cosmetique, Sanofi, and Valeant

Acknowledgments
The ECZTRA 1 and 2 studies were sponsored by LEO Pharma Medical writing and editorial assistance were provided by Kathryn Woods, PhD, and
Jane Beck, MA, from McCann Health, funded by LEO Pharma