Date: 2017-09-07
Type of
information: Results
phase: 2
Announcement: results
Company: Abbvie (USA - IL)
Product: upadacitinib (ABT-494)
Action
mechanism:
- JAK inhibitor/tyrosine kinase inhibitor. Upadacitinib is an investigational oral agent engineered to selectively inhibit JAK1, which plays an important role in the pathophysiology of immune-mediated disorders. It has been discovered and developed by AbbVie.
Disease: atopic dermatitis
Therapeutic
area: Autoimmune diseases - Dermatological diseases
Country: Australia, Belgium, Canada, Finland, Germany, Japan, Netherlands, Spain, USA
Trial
details:
- This study is an ongoing 88-week Phase 2b, randomized, double-blind, parallel-group, placebo-controlled multicenter study designed to evaluate the safety and efficacy of upadacitinib in adult patients with moderate to severe atopic dermatitis. In Period 1, subjects were randomized in a 1:1:1:1 ratio to one of four treatment groups (three dosing groups and one placebo group) for 16 weeks. The primary endpoint of the study was mean percentage change in Eczema Area and Severity Index (EASI) score at 16 weeks in comparison with placebo. Key secondary endpoints included proportion of patients achieving EASI 90, EASI 75, an Investigator Global Assessment (IGA) of 0 or 1 and percent change in pruritus/itch numerical rating scale from day 1 (baseline) to week 16 in comparison with placebo. (NCT02925117).
Latest
news:
- • On September 7, 2017, AbbVie announced positive top-line results from the Phase 2b randomized, placebo-controlled, dose-ranging study of upadacitinib (ABT-494), an investigational, once-daily oral JAK1-selective inhibitor, in adult patients with moderate to severe atopic dermatitis not adequately controlled by topical treatments, or for whom topical treatments were not medically advisable.1 In this study, all upadacitinib dose groups (30/15/7.5 mg once-daily) met the primary endpoint (mean percent change in EASI at week 16 versus placebo).
- Results at week 16 showed that across all doses, the primary and all skin and itch-specific secondary endpoints, patients treated with upadacitinib achieved improvements that were statistically significant compared to placebo (p<0.05).1 Additionally, reduction in itch was observed within the first week and improvement in skin within the first two weeks (p<0.001 across all doses).
- The mean percent change from baseline in the EASI score, a measure of the extent and severity of atopic dermatitis and the primary endpoint in this study, was 74/62/39 percent for patients receiving the 30/15/7.5 mg doses of upadacitinib, respectively, compared to 23 percent for patients receiving placebo (p<0.001/0.001/0.05, respectively). A 75 percent improvement in disease (EASI 75) was achieved by 69/52/29 percent of patients receiving the 30/15/7.5 mg doses of upadacitinib respectively, compared to 10 percent for patients receiving placebo (p<0.001/0.001/0.05, respectively).
- Disease improvement of 90 percent or more (EASI 90) was achieved by 50/26/14 percent of patients receiving the 30/15/7.5 mg doses of upadacitinib, respectively, compared to 2 percent for patients receiving placebo (p<0.001/0.01/0.05, respectively). Correspondingly, clear or almost clear skin was achieved by 50/31/14 percent of patients receiving the 30/15/7.5 mg doses of upadacitinib, as measured by the Investigator's Global Assessment scale (IGA 0 or 1), compared to 2 percent of patients receiving placebo (p<0.001/0.001/0.05, respectively).
- In addition, significant improvement was observed with respect to pruritus (itch). Patients treated with upadacitinib experienced 69/48/40 percent improvement in itch across the 30/15/7.5 mg upadacitinib doses, as measured by the pruritus numerical rating scale (NRS), compared to 10 percent for patients receiving placebo (p<0.001/0.001/0.01, respectively).
- In addition, significant improvement was observed with respect to pruritus (itch). Patients treated with upadacitinib experienced 69/48/40 percent improvement in itch across the 30/15/7.5 mg upadacitinib doses, as measured by the pruritus numerical rating scale (NRS), compared to 10 percent for patients receiving placebo (p<0.001/0.001/0.01, respectively).
-
|
Dose
|
Mean
percentage
change in EASI
score****
|
EASI 75****
|
EASI 90****
|
Investigator
Global
Assessment
(IGA) of "0" or
"1"*****
|
Percent
change in
pruritus/itch
numerical
rating
scale******
|
|
30 mg (n=42)
|
74%***
|
69%***
|
50%***
|
50%***
|
69%***(N=42)
|
|
15 mg (n=42)
|
62%***
|
52%***
|
26%**
|
31%***
|
48%***(N=37)
|
|
7.5 mg (n=42)
|
39%*
|
29%*
|
14%*
|
14%*
|
40%**(N=40)
|
|
Placebo (n=41)
|
23%(N=39)
|
10%
|
2%
|
2%
|
10%(N=37)
|
-
*p<0.05, **p<0.01, ***p<0.001
|
****Eczema Area and Severity Index (EASI) score is a tool used to measure the extent (area) and severity of atopic eczema; EASI 75 is defined as at least a 75 percent reduction in EASI score relative to the baseline (day 1); EASI 90 is defined as at least a 90 percent reduction in EASI score relative to the baseline (day 1).
|
*****The Investigator's Global Assessment (IGA) is a 5-point scale used to measure the severity of disease at the time of the investigator's evaluation of the participant ranging from 0 (clear, no inflammatory signs of AD) to 4 (severe erythema and severe papulation/infiltration with or without oozing/crusting).
|
******Itch will be rated from 0 (no itch) to 10 (worst imaginable itch).
|
- In this study, no new safety signals were detected. The most common adverse events were upper respiratory tract infection, atopic dermatitis and acne.1 Serious adverse events across treatment groups occurred in 2/1/0 patients in the 7.5/15/30 mg groups compared to 1 patient on placebo. No herpes zoster, malignancies, deaths or cases of pulmonary embolism (PE) or deep vein thrombosis (DVT) occurred in this Phase 2b study.1 The safety profile of upadacitinib in this patient population will be further evaluated in the Phase 3 program.
Is
general: Yes
