Efficacy and Safety Study of QAW039 in the Treatment of P... | NCT01785602

ID	Type	Description	Link
2012-005321-78	EudraCT Number

Status Module

Label	Type	Description	Intervention Names
QAW039	Experimental	Participants received QAW039 450 mg daily by mouth.	Drug: QAW039
Placebo	Placebo Comparator	Participants received matching placebo to QAW039.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
QAW039	Drug	Capsules	QAW039
Placebo

Outcomes Module

Primary Outcomes

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 Outcomes

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.

Eligibility Module

Eligibility Criteria

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

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Phillip	Australian Capital Territory	2606	Australia
Novartis Investigative Site

Results Section

Participant Flow Module

ID	Title	Description
FG000	QAW039	Participants received QAW039 450 mg daily by mouth.
FG001	Placebo	Participants received matching placebo to QAW039.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

ID	Title	Description
BG000	QAW039	Participants received QAW039 450 mg daily by mouth.
BG001	Placebo	Participants received matching placebo to QAW039.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00076 BG00127 BG002103

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

All randomized participants

Posted

Mean

Standard Error

Score on a scale

Baseline, 12 weeks

ID	Title	Description
OG000	QAW039	Participants received QAW039 450 mg daily by mouth.
OG001	Placebo	Participants received matching placebo to QAW039.

Units	Counts
Participants	OG00076 OG00127

Title

Denominators

Categories

Title	Measurements
	OG000-8.65± 0.010 OG001-6.95± 0.017

Secondary

Change From Baseline in Eczema Area and Severity Index

All randomized participants

Posted

Mean

Standard Error

Score on a scale

Baseline, 4 weeks, 8 weeks

ID	Title	Description
OG000	QAW039	Participants received QAW039 450 mg daily by mouth.
OG001	Placebo	Participants received matching placebo to QAW039.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0004 affected76 at risk EG0011 affected27 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0003 affected76 at risk EG0012 affected27 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG00010 affected76 at risk EG0012 affected27 at risk
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0006 affected76 at risk EG0013 affected27 at risk
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0005 affected76 at risk EG0011 affected27 at risk
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG00011 affected76 at risk EG0011 affected27 at risk
Oral herpes	Infections and infestations	MedDRA	Systematic Assessment	EG0004 affected76 at risk EG0011 affected27 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected76 at risk EG0012 affected27 at risk
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0003 affected76 at risk EG0012 affected27 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0007 affected76 at risk EG0014 affected27 at risk
Hypoaesthesia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected76 at risk EG0012 affected27 at risk
Tension headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected76 at risk EG0012 affected27 at risk
Dermatitis atopic	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG00024 affected76 at risk EG0019 affected27 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0003 affected76 at risk EG0012 affected27 at risk
Hot flush	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected76 at risk EG0012 affected27 at risk

ID	Term
D003876	Dermatitis, Atopic
D012871	Skin Diseases

ID	Term
D012873	Skin Diseases, Genetic
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D003872	Dermatitis
D017437	Skin and Connective Tissue Diseases
D017443	Skin Diseases, Eczematous
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	QAW039	Participants received QAW039 450 mg daily by mouth.			1	76	44	76
EG001	Placebo	Participants received matching placebo to QAW039.			4	27	16	27

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial fibrillation	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected76 at risk EG0010 affected27 at risk
Diverticulitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected76 at risk EG0011 affected27 at risk
Dermatitis atopic	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected76 at risk EG0013 affected27 at risk