Effect of OC000459 on Moderate to Severe Atopic Dermatitis

• Sponsor: Atopix Therapeutics, Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02002208
• Collaborator: (none)
• Enrollment: 142
• Location: 1
• Arms: 2
• Duration (Months): 28
• Patients Per Site Per Month: 5.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether OC000459 is in reducing disease severity and preventing flares in people with moderate to severe atopic dermatitis (AD).

Condition or Disease	Intervention/Treatment	Phase
Atopic Dermatitis	Drug: OC000459	Phase 2

Detailed Description

The study will include patients with a Th2 high eosinophilic phenotype who typically have more severe disease and are prone to flare.

Study Design

• Study Type: Interventional
• Actual Enrollment: 142 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Study of the Effect of OC000459 on Signs and Symptoms in Subjects With Moderate to Severe Atopic Dermatitis: A Randomised Double Blind Placebo Controlled Parallel Group Study
• Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Feb 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OC000459 Tablets 50 mg orally once a day	Drug: OC000459; Oral CRTH2 antagonist; Other Names: timapiprant
Placebo Comparator: Placebo Tablets Orally once a day	Drug: OC000459; Oral CRTH2 antagonist; Other Names: timapiprant

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Eczema Area and Severity Index (EASI) Compared to Placebo at Week 16 [EASI was measured at baseline (week 0) and 16 weeks after dosing.]

   The EASI scoring system uses a defined process to grade the severity of the signs of eczema and the extent affected in four regions of the body: head and neck, trunk, upper extremities and lower extremities. The scale ranges from 0 to 72 and the severity strata for the EASI are as follows: 0 clear; 0.1-1.0 almost clear; 1.1-7.0 mild; 7.1-21.0 =moderate; 21.1-50.0 severe; 50.1-72.0 very severe. When assessing response to therapy a reduction of 7 or more is considered to be clinically meaningful.

Secondary Outcome Measures

1. Rate of Flares [over 16 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 48 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Atopic dermatitis as defined by a score of at least 9 on the Nottingham Eczema Severity Score, stratified into moderate (score 9 to 11 inclusive) and severe (score 12 to 15 inclusive) disease.

2. Fully documented history of the use of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI). Subjects without a fully documented history will be excluded from the study.

3. Male and female subjects with moderate to severe atopic dermatitis treated with by TCS and/or TCI (with or without emollients) at the time of screening and over the previous month.

4. Subjects must have had at least 1 AD flare in the previous 6 months.

Exclusion Criteria:

1. Receipt of any forbidden medication including over the counter preparations and herbal medicines within 14 days of the first dosing day with the exception of paracetamol up to a maximum of 2g daily.

2. Use of systemic steroids within 4 weeks of the screening visit, light therapy or immunosuppressants within 2 months of the screening visit.

3. Use of NSAIDs.

4. Subjects initially diagnosed with AD aged 2 years or over will be excluded unless they have either coexisting or a history of asthma and/or allergic rhinoconjunctivitis.

5. Subjects with contact dermatitis will be excluded.

6. Subjects with acute skin infection or acute disease flares. Subjects with active flares during the screening to randomisation period (visits 1 to 2) may be managed according to normal clinical practice and be rescreened once their flares are no longer active.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Sheffield	Sheffield		United Kingdom

Sponsors and Collaborators

• Atopix Therapeutics, Ltd.

Investigators

• Principal Investigator: Michael Cork, MB, University of Sheffield

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Atopix Therapeutics, Ltd.
• ClinicalTrials.gov Identifier: NCT02002208
• Other Study ID Numbers: OC000459/017/13
• First Posted: Dec 5, 2013
• Last Update Posted: Mar 26, 2018
• Last Verified: Feb 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Dermatitis, Atopic; Dermatitis; Eczema

Study Results

Participant Flow

Recruitment Details	142 patients were randomised. One patient withdrew prior to dosing meaning that there was 141 patients in the safety set. 2 further patients withdrew prior to the first efficacy measurement which means there were 139 patients in the full analysis set.

Arm/Group Title	OC000459 Tablets	Placebo Tablets
Arm/Group Description	50 mg orally once a day OC000459: CRTH2 inhibitor	Orally once a day OC000459: CRTH2 inhibitor
Period Title: Overall Study
STARTED	69	70
COMPLETED	32	30
NOT COMPLETED	37	40

Baseline Characteristics

Arm/Group Title	OC000459 Tablets	Placebo Tablets	Total
Arm/Group Description	50 mg orally once a day OC000459: CRTH2 inhibitor	Orally once a day OC000459: CRTH2 inhibitor	Total of all reporting groups
Overall Participants	69	70	139
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31.6 (8.42)	30.9 (8.54)	31.2 (8.46)
Sex: Female, Male (Count of Participants)
Female	29 42%	31 44.3%	60 43.2%
Male	40 58%	39 55.7%	79 56.8%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Eczema Area and Severity Index (EASI) Compared to Placebo at Week 16
Description	The EASI scoring system uses a defined process to grade the severity of the signs of eczema and the extent affected in four regions of the body: head and neck, trunk, upper extremities and lower extremities. The scale ranges from 0 to 72 and the severity strata for the EASI are as follows: 0 clear; 0.1-1.0 almost clear; 1.1-7.0 mild; 7.1-21.0 =moderate; 21.1-50.0 severe; 50.1-72.0 very severe. When assessing response to therapy a reduction of 7 or more is considered to be clinically meaningful.
Time Frame	EASI was measured at baseline (week 0) and 16 weeks after dosing.

Outcome Measure Data

Analysis Population Description

Adjusted mean change from baseline EASI at Week 16

Arm/Group Title	OC000459 Tablets	Placebo Tablets
Arm/Group Description	50 mg orally once a day OC000459: CRTH2 inhibitor	Orally once a day
Measure Participants	69	70
Mean (Standard Error) [units on a scale]	-3.8 (1.72)	-6.1 (1.71)

2. Secondary Outcome

Title	Rate of Flares
Time Frame	over 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	OC000459 Tablets	Placebo Tablets
Arm/Group Description	50 mg orally once a day OC000459: CRTH2 inhibitor	Orally once a day
Measure Participants	69	70
Mean (Standard Deviation) [flares]	2.879 (2.8679)	2.646 (4.7922)

Adverse Events

Time Frame	Up to 6 months
Adverse Event Reporting Description	Standardised coding using MedDRA
Arm/Group Title	OC000459 Tablets		Placebo Tablets
Arm/Group Description	50 mg orally once a day OC000459: CRTH2 inhibitor		Orally once a day
All Cause Mortality
	OC000459 Tablets		Placebo Tablets
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	OC000459 Tablets		Placebo Tablets
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/70 (2.9%)		6/71 (8.5%)
Blood and lymphatic system disorders
Solitary Plasmacytoma	1/70 (1.4%)		0/71 (0%)
Gastrointestinal disorders
Gastroenteritis	0/70 (0%)		1/71 (1.4%)
Immune system disorders
Anaphylaxis	0/70 (0%)		1/71 (1.4%)
Infections and infestations
Staphylococcal infection	0/70 (0%)		1/71 (1.4%)
Investigations
ECG abnormality	0/70 (0%)		1/71 (1.4%)
Skin and subcutaneous tissue disorders
Worsening atopic dermatitis	1/70 (1.4%)		3/71 (4.2%)
Other (Not Including Serious) Adverse Events
	OC000459 Tablets		Placebo Tablets
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	52/70 (74.3%)		47/71 (66.2%)
Eye disorders
Conjunctivitis	2/70 (2.9%)		1/71 (1.4%)
Gastrointestinal disorders
Nausea	3/70 (4.3%)		4/71 (5.6%)
Tooth ache	0/70 (0%)		3/71 (4.2%)
Abdominal pain	3/70 (4.3%)		1/71 (1.4%)
Diarrhoea	2/70 (2.9%)		2/71 (2.8%)
Abdominal distension	0/70 (0%)		2/71 (2.8%)
Dyspepsia	0/70 (0%)		2/71 (2.8%)
General disorders
Fatigue	0/70 (0%)		3/71 (4.2%)
Chest pain	2/70 (2.9%)		0/71 (0%)
Influenza like illness	2/70 (2.9%)		0/71 (0%)
Immune system disorders
Food allergy	1/70 (1.4%)		2/71 (2.8%)
Infections and infestations
Nasopharyngitis	9/70 (12.9%)		15/71 (21.1%)
Herpes simplex	4/70 (5.7%)		2/71 (2.8%)
Cystitis	2/70 (2.9%)		0/71 (0%)
Ear infection	0/70 (0%)		2/71 (2.8%)
Rash pustular	2/70 (2.9%)		0/71 (0%)
Tonsillitis	0/70 (0%)		2/71 (2.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/70 (2.9%)		2/71 (2.8%)
Back pain	1/70 (1.4%)		2/71 (2.8%)
Nervous system disorders
Headache	15/70 (21.4%)		15/71 (21.1%)
Disturbance in attention	0/70 (0%)		2/71 (2.8%)
Dizziness	0/70 (0%)		2/71 (2.8%)
Psychiatric disorders
Insomnia	2/70 (2.9%)		0/71 (0%)
Panic attack	0/70 (0%)		2/71 (2.8%)
Sleep disorder	0/70 (0%)		2/71 (2.8%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/70 (1.4%)		3/71 (4.2%)
Skin and subcutaneous tissue disorders
Pruritus	6/70 (8.6%)		4/71 (5.6%)
Dermatitis atopic	6/70 (8.6%)		5/71 (7%)
Dermatitis	0/70 (0%)		2/71 (2.8%)
Hyperhidrosis	0/70 (0%)		2/71 (2.8%)
Night sweats	0/70 (0%)		2/71 (2.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.