Efficacy and Safety Study of QAW039 in the Treatment of Patients With Moderate to Severe Atopic Dermatitis.

A Randomized, Double-blind, Placebo-controlled, Parallel Group Study Evaluating Efficacy and Safety of QAW039 in the Treatment of Patients With Moderate to Severe Atopic Dermatitis

The purpose of this study is to determine whether QAW039 is safe and has beneficial effects in people who have moderate to severe atopic dermatitis (AD).

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Placebo; Drug: QAW039

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Phillip, Australian Capital Territory, Australia, 2606
      • Novartis Investigative Site
  • Queensland
    • Benowa, Queensland, Australia, 4217
      • Novartis Investigative Site
    • Woolloongabba, Queensland, Australia, 4102
      • Novartis Investigative Site
• Austria
  • Vienna, Austria
    • Novartis Investigative Site
• Belgium
  • Bruxelles, Belgium, 1200
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
  • Liège, Belgium, 4000
    • Novartis Investigative Site
• Bulgaria
  • Sofia, Bulgaria, 1612
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 10117
    • Novartis Investigative Site
  • Berlin, Germany, 10098
    • Novartis Investigative Site
  • Bonn, Germany, 53105
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Muenster, Germany, 48149
    • Novartis Investigative Site
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Novartis Investigative Site
  • Groningen, Netherlands
    • Novartis Investigative Site
  • Utrecht, Netherlands, 3508 GA
    • Novartis Investigative Site
• Romania
  • Bucharest, Romania, 011461
    • Novartis Investigative Site
• South Africa
  • Durban, South Africa, 4001
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Presence of atopic dermatitis confirmed by Itchy skin condition in the past 12 months plus three, or more, of the following:

  • History of involvement of the skin creases (fronts of elbows, behind knees, fronts of ankles, around neck or around eyes)
  • Personal history of asthma or hay fever
  • History of generally dry skin in the past year
  • Onset before age of 2 years
  • Visible flexural dermatitis
• Patients with an EASI score of ≥15 at screening and stable AD (not currently experiencing an acute flare of their AD).
• Patients that have been treated with topical corticosteroids or topical calcineurin inhibitors on at least one occasion, or could not use topical drugs (due to contraindications, side effects, etc.) and are candidates for or have previously received systemic treatment.

Key Exclusion Criteria:

• History of hypersensitivity to any of the study drugs (including local anesthesia) or to drugs of similar chemical classes (CRTh2 antagonists)
• History of serious allergic reactions to any allergen, such as anaphylactic shock or life-threatening asthma, prior intubation, respiratory arrest, hospitalization due to asthma within the last 3 months or seizures as a result of asthma
• History of clinically significant ECG abnormalities or screening/baseline ECG that demonstrated clinical significant abnormalities which could affect patient safety or interpretation of study results
• History of long QT syndrome or whose QTc interval (Frederica's) was prolonged (>450 msec for males and females) at screening
• Use of topical prescription treatment (e.g., topical corticosteroids, calcineurin inhibitors, antibiotics, etc.) within two weeks prior to initial dosing of study drug. Patient use of emollients was encouraged
• Exception: For local atopic dermatitis flares during this 2-week interval, mild topical corticosteroids may be taken short term (up to one week)
• Recent previous systemic treatment with phototherapy, systemic antihistamines, immunosuppressive agents (e.g., cyclosporine, mycophenolate, or oral tacrolimus, including therapeutic proteins)
• Patients on maintenance immunotherapy who either began their allergen specific immunotherapy regimen or had a clinically relevant change to their immunotherapy within one month prior to granting informed consent
• Patients on high-dose statin therapy (>40 mg fluvastatin or 20 mg simvastatin, atorvastin, pravastatin, or rosuvastatin [10 mg if Asian])
• Excessive exposure to UV light in the three weeks prior to study start (screening), including tanning and sun beds and/or planning excessive sunbathing or beach holidays with associated sun bathing during the treatment period
• History of hypertrophic scarring
• Body mass index <17 or >40 kg/m2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QAW039; Participants received QAW039 450 mg daily by mouth.	Drug: QAW039; Capsules
Placebo Comparator: Placebo; Participants received matching placebo to QAW039.	Drug: Placebo; Capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Eczema Area and Severity Index (EASI)	Investigators assessed presence and severity of erythema, induration/papulation, excoriation, and lichenification in four body areas: head/neck (H), upper limbs (UL), trunk (T), and lower limbs (LL). Investigators assigned a severity score from 0 - 3 for each area (none=0, mild=1, moderate=2, and severe=3). Investigators could assign half-points. Investigators also assigned an area score from 0 (no atopic dermatitis lesion in the area) to 6 (entire area is affected) for each area. The weighting factor was 0.1 for head/neck, 0.2 for upper limbs, 0.3 for trunk, and 0.4 for lower limbs. The total body score for each body region was obtained by multiplying the sum of the severity scores of the four key signs by the area score, then multiplying the result by the constant weighted value assigned to that body region. The sum of these scores gave the EASI total, ranging from 0 to 72. A higher score represented greater disease severity. A negative change from baseline indicates improvement.	Baseline, 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Eczema Area and Severity Index	Investigators assessed presence and severity of erythema, induration/papulation, excoriation, and lichenification in four body areas: head/neck (H), upper limbs (UL), trunk (T), and lower limbs (LL). Investigators assigned a severity score from 0 - 3 for each area (none=0, mild=1, moderate=2, and severe=3). Investigators could assign half-points. Investigators also assigned an area score from 0 (no atopic dermatitis lesion in the area) to 6 (entire area is affected) for each area. The weighting factor was 0.1 for head/neck, 0.2 for upper limbs, 0.3 for trunk, and 0.4 for lower limbs. The total body score for each body region was obtained by multiplying the sum of the severity scores of the four key signs by the area score, then multiplying the result by the constant weighted value assigned to that body region. The sum of these scores gave the EASI total, ranging from 0 to 72. A higher score represented greater disease severity. A negative change from baseline indicates improvement.	Baseline, 4 weeks, 8 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: February 5, 2013
• First Submitted That Met QC Criteria: February 6, 2013
• First Posted (Estimate): February 7, 2013

Study Record Updates

• Last Update Posted (Estimate): December 15, 2015
• Last Update Submitted That Met QC Criteria: November 11, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Skin Diseases; Atopic eczema
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: CQAW039X2201; 2012-005321-78 (EudraCT Number)