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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01785602
• Collaborator: (none)
• Enrollment: 103
• Locations: 18
• Arms: 2
• Duration (Months): 17
• Patients Per Site: 5.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Atopic Dermatitis	Drug: QAW039; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 103 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Jun 1, 2013
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Nov 1, 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Eczema Area and Severity Index (EASI) [Baseline, 12 weeks]

   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.

Secondary Outcome Measures

1. Change From Baseline in Eczema Area and Severity Index [Baseline, 4 weeks, 8 weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Phillip	Australian Capital Territory	Australia	2606
2	Novartis Investigative Site	Benowa	Queensland	Australia	4217
3	Novartis Investigative Site	Woolloongabba	Queensland	Australia	4102
4	Novartis Investigative Site	Vienna		Austria
5	Novartis Investigative Site	Bruxelles		Belgium	1200
6	Novartis Investigative Site	Leuven		Belgium	3000
7	Novartis Investigative Site	Liège		Belgium	4000
8	Novartis Investigative Site	Sofia		Bulgaria	1612
9	Novartis Investigative Site	Berlin		Germany	10098
10	Novartis Investigative Site	Berlin		Germany	10117
11	Novartis Investigative Site	Bonn		Germany	53105
12	Novartis Investigative Site	Dresden		Germany	01307
13	Novartis Investigative Site	Muenster		Germany	48149
14	Novartis Investigative Site	Amsterdam		Netherlands	1105 AZ
15	Novartis Investigative Site	Groningen		Netherlands
16	Novartis Investigative Site	Utrecht		Netherlands	3508 GA
17	Novartis Investigative Site	Bucharest		Romania	011461
18	Novartis Investigative Site	Durban		South Africa	4001

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01785602
• Other Study ID Numbers: CQAW039X2201; 2012-005321-78
• First Posted: Feb 7, 2013
• Last Update Posted: Dec 15, 2015
• Last Verified: Nov 1, 2015

• Keywords provided by Novartis Pharmaceuticals: Atopic eczema; Skin Diseases
• Additional relevant MeSH terms: Dermatitis, Atopic; Dermatitis; Eczema

Study Results

Participant Flow

Arm/Group Title	QAW039	Placebo
Arm/Group Description	Participants received QAW039 450 mg daily by mouth.	Participants received matching placebo to QAW039.
Period Title: Overall Study
STARTED	76	27
COMPLETED	63	18
NOT COMPLETED	13	9

Baseline Characteristics

Arm/Group Title	QAW039	Placebo	Total
Arm/Group Description	Participants received QAW039 450 mg daily by mouth.	Participants received matching placebo to QAW039.	Total of all reporting groups
Overall Participants	76	27	103
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	35.5 (13.08)	38.7 (9.95)	36.3 (12.37)
Sex: Female, Male (Count of Participants)
Female	27 35.5%	12 44.4%	39 37.9%
Male	49 64.5%	15 55.6%	64 62.1%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Eczema Area and Severity Index (EASI)
Description	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.
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	QAW039	Placebo
Arm/Group Description	Participants received QAW039 450 mg daily by mouth.	Participants received matching placebo to QAW039.
Measure Participants	76	27
Mean (Standard Error) [Score on a scale]	-8.65 (0.010)	-6.95 (0.017)

2. Secondary Outcome

Title	Change From Baseline in Eczema Area and Severity Index
Description	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.
Time Frame	Baseline, 4 weeks, 8 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	QAW039	Placebo
Arm/Group Description	Participants received QAW039 450 mg daily by mouth.	Participants received matching placebo to QAW039.
Measure Participants	76	27
Week 4	-6.22 (0.010)	-5.89 (0.017)
Week 8	-7.49 (0.010)	-5.61 (0.017)

Adverse Events

Time Frame	Serious adverse events were collected from day 1 until 4 weeks after end of study (week 20)
Arm/Group Title	QAW039		Placebo
Arm/Group Description	Participants received QAW039 450 mg daily by mouth.		Participants received matching placebo to QAW039.
All Cause Mortality
	QAW039		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	QAW039		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/76 (1.3%)		4/27 (14.8%)
Cardiac disorders
Atrial fibrillation	1/76 (1.3%)		0/27 (0%)
Infections and infestations
Diverticulitis	0/76 (0%)		1/27 (3.7%)
Skin and subcutaneous tissue disorders
Dermatitis atopic	0/76 (0%)		3/27 (11.1%)
Other (Not Including Serious) Adverse Events
	QAW039		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/76 (57.9%)		16/27 (59.3%)
Gastrointestinal disorders
Abdominal pain	4/76 (5.3%)		1/27 (3.7%)
Abdominal pain upper	3/76 (3.9%)		2/27 (7.4%)
Diarrhoea	10/76 (13.2%)		2/27 (7.4%)
Nausea	6/76 (7.9%)		3/27 (11.1%)
General disorders
Fatigue	5/76 (6.6%)		1/27 (3.7%)
Infections and infestations
Nasopharyngitis	11/76 (14.5%)		1/27 (3.7%)
Oral herpes	4/76 (5.3%)		1/27 (3.7%)
Musculoskeletal and connective tissue disorders
Back pain	1/76 (1.3%)		2/27 (7.4%)
Nervous system disorders
Dizziness	3/76 (3.9%)		2/27 (7.4%)
Headache	7/76 (9.2%)		4/27 (14.8%)
Hypoaesthesia	0/76 (0%)		2/27 (7.4%)
Tension headache	1/76 (1.3%)		2/27 (7.4%)
Skin and subcutaneous tissue disorders
Dermatitis atopic	24/76 (31.6%)		9/27 (33.3%)
Pruritus	3/76 (3.9%)		2/27 (7.4%)
Vascular disorders
Hot flush	0/76 (0%)		2/27 (7.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.