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A Phase 2b Dose-Ranging Efficacy and Safety Study of Tralokinumab in Adult 
Patients with Moderate to Severe Atopic Dermatitis (AD)

Andreas Wollenberg,1 Michael D. Howell,2 Emma Guttman-Yassky,3 Jonathan I. Silverberg,4 Claire Birrell,5 Christopher Kell,6 Koustubh Ranade,2 Michelle Dawson,6 René van der Merwe6
1Ludwig Maximillian University, Munich, Germany; 2MedImmune, LLC, Gaithersburg, MD, USA; 3Mount Sinai School of Medicine, New York, NY, USA; 4Northwestern University Feinberg School of Medicine, 

Chicago, IL, USA; 5VHsquared Ltd, Cambridge, UK; 6MedImmune, Ltd, Cambridge, UK

Poster presented at the American Academy of Dermatology Meeting in Orlando, FL; March 3-7, 2017.

▪ Novel, well-tolerated treatments that target the molecular pathways underlying atopic dermatitis 

(AD), rather than symptomatic relief, are needed

▪ Interleukin (IL)-13, a type 2 T helper cytokine, has been implicated in the pathophysiology of 

AD1–4 and is reportedly upregulated in acute and chronic lesions5

▪ Tralokinumab is an immunoglobulin G4 human monoclonal antibody that potently and specifically 

neutralizes IL-13.6 We report the findings from a Phase 2b study of tralokinumab in patients with 

moderate to severe AD

▪ Serum dipeptidyl peptidase 4 (DPP-4) has been reported as a predictive biomarker for 

tralokinumab efficacy in patients with severe asthma7

Introduction

Figure 1. Study design

Tralokinumab 45 mg SC Q2W + TCS 

(N=51)

Tralokinumab 150 mg SC Q2W + TCS 

(N=50)

Tralokinumab 300 mg SC Q2W + TCS 

(N=51)

Placebo SC Q2W + TCS 

(N=52)

Adults aged 18–75 years, with a 

diagnosis of moderate to severe AD 

>1 year prior to screening

▪ AD involvement of ≥10% of body 

surface area

▪ EASI of ≥12

▪ SCORAD of ≥25

▪ IGA score of ≥3

Maintenance 

TCS

–2
Weeks

0

Run-in period Treatment period

–6

Screening period

2212

Follow-up period
Primary 
endpoint

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Study design

• This was a Phase 2b, randomized, double-blind, placebo-controlled, dose-ranging study 

(NCT02347176) with a 12-week treatment period (Figure 1)

• Patients were randomized to receive tralokinumab (45, 150, or 300 mg) following a 2‐week run-in 
period with Class 3 (mid-strength) topical corticosteroids (TCS, administered throughout the study) 

(Figure 1)

Assessments

Co-primary efficacy analyses (ITT [intention-to-treat] population)

• Change from baseline in total Eczema Area and Severity Index (EASI) at Week 12

• Percentage of Investigator’s Global Assessment (IGA) responders (patients achieving an IGA score 

of 0 or 1, and at least a 2-grade reduction from baseline at Week 12)

Secondary analyses (ITT population)

• Change from baseline in Scoring of Atopic Dermatitis (SCORAD)

• Change from baseline in pruritus numerical rating scale (NRS) (7-day mean score)

• Change from baseline in Dermatology Life Quality Index (DLQI)

• Percentage of patients achieving ≥50% reduction from baseline in EASI (EASI 50)

• Percentage of patients achieving ≥50% reduction from baseline in SCORAD (SCORAD 50)

• Staphylococcus aureus (S. aureus) colonization and infection were measured on lesional and non-

lesional skin

Exploratory analysis (DPP-4 subpopulations)

• Primary endpoints were assessed in a subpopulation of patients with concentrations of DPP‐4 equal 
to or above (DPP-4-high) or below (DPP-4-low) the total population median at baseline

Safety (As-treated population)

• Most frequent treatment-emergent adverse events (TEAEs) and treatment‐emergent serious 
adverse events (TESAEs)

Statistical analysis

• Continuous endpoints (change from baseline in EASI, SCORAD, pruritus NRS, and DLQI) were 

analyzed using repeated measures analysis, adjusting for baseline

• Binary endpoints (IGA, EASI 50, and SCORAD 50 responders, and S. aureus status) were analyzed 

using logistic regression, adjusting for each baseline endpoint value

• Other endpoints were summarized descriptively

Methods

Results
• 204 patients were randomized to treatment and 172 (84.3%) completed the study (Figure 2)

• Demographics and baseline disease characteristics were similar between treatment groups (Table 1)

AE, adverse event

Figure 2. Patient disposition

Discontinuation, n (%)

Lost to follow-up, 2 (3.9)

Withdrawal of consent, 8 (15.7)

AE, 1 (2.0)

Other, 3 (5.9)

Total, 14 (27.5)

Placebo

(N=51)

Randomized (n=204)

Patients/ screened (n=299) Screening failures (n=95)

Did not meet inclusion/exclusion 

criteria (n=76)

Lost to follow-up (n=4)

Withdrawal of consent (n=9)

Other (n=6)

Discontinuation, n (%)

Lost to follow-up, 1 (2.0)

Withdrawal of consent, 3 (6.0)

AE, 1 (2.0)

Other, 2 (4.0)

Total, 7 (14.0)

Tralokinumab

45 mg (N=50)

Discontinuation, n (%)

Lost to follow-up, 0

Withdrawal of consent, 

3 (5.9)

AE, 2 (3.9)

Other, 2 (3.9)

Total, 7 (13.7)

Tralokinumab

150 mg (N=51)

Discontinuation, n (%)

Lost to follow-up, 1 (1.9)

Withdrawal of consent, 

3 (5.8)

AE, 0

Other, 0

Total, 4 (7.7)

Tralokinumab

300 mg (N=52)

Tralokinumab + TCS

Placebo Q2W 

(N=51)

45 mg Q2W 

(N=50)

150 mg Q2W 

(N=51)

300 mg Q2W 

(N=52)

Age, years, mean (SD) 39.4 (14.5) 39.1 (15.1) 37.1 (14.0) 35.7 (14.6)

Male, n (%) 22 (43.1) 29 (58.0) 26 (51.0) 33 (63.5)

Racea, n (%)

Asian 10 (19.6) 11 (22.0) 8 (15.7) 16 (30.8)

Black or African-American  8 (15.7) 4 (8.0) 10 (19.6) 7 (13.5)

White 31 (60.8) 33 (66.0) 33 (64.7) 28 (53.8)

Other 1 (2.0) 1 (2.0) 0 0

Total EASI, mean (SD) 26.4 (12.6) 24.8 (8.3) 27.1 (11.2) 27.3 (10.9)

Baseline IGAb, n (%)

Moderate 31 (60.8) 32 (64.0) 31 (60.8) 29 (55.8)

Severe 20 (39.2) 18 (36.0) 16 (31.4) 20 (38.5)

Very severe 0 0 4 (7.8) 3 (5.8)

Total SCORAD, mean (SD) 58.5 (12.9) 57.5 (12.6) 60.8 (11.9) 60.8 (12.3)

Table 1. Demographics and baseline disease characteristics (ITT population)

aEach race category contains patients who only selected this category
bPer the inclusion/exclusion criteria, no patient had a baseline IGA of clear, almost clear or mild EASI, Eczema Area and Severity Index; 

IGA, Investigator’s Global Assessment; ITT, intention-to-treat; Q2W, every 2 weeks; SCORAD, Scoring of Atopic Dermatitis; 

SD, standard deviation; TCS, topical corticosteroids

Efficacy

Primary analyses

• At Week 12, tralokinumab 150 mg and 300 mg significantly reduced total EASI from baseline 

(adjusted mean difference [standard error; SE]: –4.4 [2.0] p=0.027 and –4.9 [1.9] p=0.011, 

respectively), compared with placebo (Figure 3A)

• A greater number of patients treated with tralokinumab 150 mg and 300 mg had an IGA response 

of 0 or 1 at Week 12, compared with placebo (Figure 3B)

Figure 3. Adjusted mean change from baseline in EASI (A) and the percentage of 

patients with an IGA response at Week 12 (B) (ITT population)

Secondary analyses

• A significant decrease in SCORAD from baseline to Week 12 was demonstrated for tralokinumab 

150 mg (p=0.003) and 300 mg (p=0.002), compared with placebo (Figure 4A)

• Patients treated with tralokinumab had lower pruritus scores at Week 12, compared with placebo 

(Figure 4B)

• Treatment with tralokinumab 300 mg was associated with a significant decrease in DLQI score at 

Week 12 (p=0.006), compared with placebo (Figure 4C)

• At Week 12, tralokinumab 300 mg significantly reduced S. aureus colonization on lesional and non-

lesional skin, compared with placebo (p<0.001)

Figure 4. Adjusted mean change from baseline in SCORAD (A), pruritus NRS (B), and 

DLQI (C) (ITT population)

DLQI, Dermatology Life Quality Index; ITT, intention-to-treat; NRS, numerical rating scale; SCORAD, Scoring of Atopic Dermatitis; 

SE, standard error; TCS, topical corticosteroids

Placebo + TCS

Tralokinumab 45 mg + TCS

Tralokinumab 150 mg + TCS

Tralokinumab 300 mg + TCS

–30

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EASI, Eczema Area and Severity Index; IGA, Investigator’s Global Assessment; ITT, intention-to-treat; SE, standard error; 

TCS, topical corticosteroids

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Placebo + TCS

Tralokinumab 150 mg + TCS

Tralokinumab 45 mg + TCS

Tralokinumab 300 mg + TCS

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*
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*p≤0.05, compared with placebo

• 37 (73.1%) patients treated with tralokinumab 300 mg reached EASI 50, demonstrating a significant increase of 

21.4% (p=0.025) in response rates, compared with placebo (Figure 5A)

• Significantly more patients treated with tralokinumab 150 mg (p=0.007) and tralokinumab 300 mg (p=0.007) 

achieved SCORAD 50 at Week 12, compared with placebo (Figure 5B)

Figure 5. Percentage of patients achieving EASI 50 (A) and SCORAD 50 (B) at Week 12 (ITT population)

A) B)

n=50 n=50 n=51 n=51

n=50 n=50

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67.0
73.1

Exploratory analysis

• At Week 12, all doses of tralokinumab demonstrated a significant reduction in EASI from baseline compared 

with placebo (p<0.05) for patients in the DPP-4-high subpopulation

• Tralokinumab 300 mg demonstrated a significant increase in IGA response at Week 12 compared with 

placebo (p=0.025) for patients in the DPP-4-high subpopulation. Numerical improvements were observed for 

all treatment groups, compared with placebo

• Significant differences in either primary endpoint were not observed for the DPP‐4‐low subpopulation at 
Week 12 (Figure 6)

Figure 6. Adjusted mean change from baseline in EASI (DPP-4-low [A] and ‐high [B] subpopulations) 
and the percentage of patients with an IGA response at Week 12 (DPP-4-low [C] and -high [D] 

subpopulations)

DPP-4, dipeptidyl peptidase 4; EASI, Eczema Area and Severity Index; IGA, Investigator’s Global Assessment; SE, standard error; TCS, topical 

corticosteroids

C) D)

22

B)

Weeks

–25

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n=24 n=25 n=23 n=29n=26 n=25 n=28 n=21

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EASI, Eczema Area and Severity Index; ITT, intention-to-treat; SCORAD, Scoring of Atopic Dermatitis; TCS, topical corticosteroids 

Safety

• TEAEs and TESAEs are shown in Table 2

Tralokinumab + TCS

Placebo Q2W
(N=51)

45 mg Q2W 
(N=50)

150 mg Q2W 
(N=51)

300 mg Q2W 
(N=52)

Total 

(N=204)

At least one TEAE, n (%) 31 (60.8) 36 (72.0) 35 (68.6) 30 (57.7) 132 (64.7)

At least one TEAE leading to 

discontinuationa, n (%)
5 (9.8) 2 (4.0) 3 (5.9) 0 10 (4.9)

Most common TEAEs, occurring in ≥5% of patients, n (%)

Nasopharyngitis 5 (9.8) 11 (22.0) 6 (11.8) 12 (23.1) 34 (16.7)

Upper respiratory tract infection 5 (9.8) 5 (10.0) 5 (9.8) 4 (7.7) 19 (9.3)

Headache 2 (3.9) 3 (6.0) 4 (7.8) 4 (7.7) 13 (6.4)

AD 4 (7.8) 3 (6.0) 3 (5.9) 3 (5.8) 13 (6.4)

At least one TESAE, n (%) 1 (2.0) 3 (6.0) 2 (3.9) 0 6 (2.9)

aOne patient treated with tralokinumab 45 mg withdrew consent for further participation in the study and began treatment with cyclosporine A and 

clobegalen cream for AD. The patient later died from a cardiac event that was not considered related to treatment with tralokinumab

AD, atopic dermatitis; Q2W, every 2 weeks; TCS, topical corticosteroids; TEAE, treatment-emergent adverse event; TESAE, treatment-emergent serious 

adverse event

Table 2. TEAEs and TESAEs (As-treated population)

• In this Phase 2b study of patients with moderate to severe AD symptoms (despite daily treatment with Class 3 

TCS), tralokinumab demonstrated efficacy in the primary and key secondary endpoints, and an acceptable 

safety and tolerability profile, compared with placebo

• Furthermore, tralokinumab demonstrated significant improvements in quality of life (as shown by reduction in 

DLQI) and pruritus, compared with placebo

• Patients treated with tralokinumab 300 mg in the DPP-4-high subgroup demonstrated significant efficacy in 

both primary endpoints compared with placebo; the observed effect sizes were greater than in the ITT 

population, suggesting that DPP-4 may serve as a predictive biomarker for patients who may benefit from 

tralokinumab treatment

• However, treatment with Class 3 TCS may have impacted on efficacy effect sizes observed, providing a 

limitation to the study design

• These data suggest that targeting IL-13 is a promising approach for AD treatment. Clinical efficacy and dose 

response across a range of relevant endpoints supports the further evaluation of tralokinumab in this disease

• 6/204 (2.9%) patients had a TEAE of conjunctivitis during the study (2 [3.9%],1 [2.0%], and 3 [5.9%] were 

treated with placebo, and tralokinumab 45 and 150 mg, respectively)

• Injection-site reactions of incidence ≥1% were bruising (1.0%), pain (1.5%), and reaction (1.0%). Of these, all 

patients were treated with tralokinumab except for 1 patient in the placebo group who experienced some 

injection-site pain

Conclusions

References

1. Kim BE, et al. Clin Immunol 2008;126:332–337.

2. Howell MD, et al. J Invest Dermatol 2008;128:2248–2258.

3. Eyerich K, et al. J Allergy Clin Immunol 2009;123:59–66.

4. Khattri S, et al. J Allergy Clin Immunol 2014;133:1626–1634.

5. Gittler JK, et al. J Allergy Clin Immunol 2012;130:1344–1354.

6. May RD, et al. Br J Pharmacol 2012;166:177–193.

7. Panettieri RA, et al. Clin Invest 2015;5:701–711.

Acknowledgments

This study was funded by MedImmune. Medical writing 

support was provided by Rebecca Plant, MSc, QXV 

Communications (an Ashfield business, part of UDG 

Healthcare plc), Macclesfield, UK, and was funded by 

MedImmune.

Disclosures

A. Wollenberg is a consultant for Almirall, Celgene, LEO Pharma, L’Oreal, MedImmune, Novartis Pharma, Pierre Fabre, and 

Regeneron. M.D. Howell, C. Kell, K. Ranade, M. Dawson, and R. van der Merwe are shareholders of MedImmune. E. 

Guttman-Yassky received research support from Celgene, Eli Lilly, Glenmark Generics Inc., Janssen Pharmaceuticals Inc., 

LEO Pharmaceuticals, MedImmune, Novartis, Regeneron, and Vitae, and is a consultant for AbbVie, Anacor Pharmaceuticals 

Inc., Celgene, Dermira, Galderma Research & Development LLC, Glenmark Generics Inc., LEO Pharmaceuticals, 

MedImmune, Novartis, Pfizer, Regeneron, Sanofi-Aventis, Steifel/GlaxoSmithKline, Vitae, Mitsubishi Pharma, Eli Lilly, Asana 

Biosciences, Kyowa Hakko Kirin Pharma Inc., and Almirall. J.I. Silverberg is a consultant for Anacor, AbbVie, 

GlaxoSmithKline, Eli Lilly, MedImmune, Pfizer, and Regeneron Sanofi. C. Birrell is a shareholder of AstraZeneca.  

Placebo + TCS

Tralokinumab 150 mg + TCS

Tralokinumab 45 mg + TCS

Tralokinumab 300 mg + TCS

Placebo + TCS

Tralokinumab 150 mg + TCS

Tralokinumab 45 mg + TCS

Tralokinumab 300 mg + TCS

EASI, Eczema Area and Severity Index; IGA, Investigator’s Global Assessment; Q2W, every 2 weeks; SC, subcutaneous; 

SCORED, Scoring of Atopic Dermatitis; TCS, topical corticosteroids

MedImmune’s product mentioned is investigational and not approved in any country.