Clinical trial NCT02031679: Efficacy and Safety of Chemoattractant Receptor-homologous Molecule Expressed on T Helper Type 2 (CRTh2) Antagonist AZD1981 in Chronic Idiopathic Urticaria (CIU) Antihistamines
Official title: A Phase IIa, Randomized, Placebo-controlled, Double-blind Study to Assess the Efficacy and Safety of the CRTh2 Antagonist AZD1981 in Patients With Chronic Idiopathic Urticaria (CIU) Who Are Refractory to H1 Antihistamines
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Idiopathic Urticaria
Keywords: Chronic Idiopathic Urticaria
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2014-01-09
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators are recruiting for a chronic hives study. This research is being done to test whether an investigational drug called AstraZeneca drug (AZD)1981 may be helpful for treating people with Chronic Idiopathic Urticaria who continue to have symptoms despite taking antihistamines. The word "investigational" means that AZD1981 is not approved for marketing by the Food and Drug Administration (FDA). The FDA is allowing the use of AZD1981 in this study.

People with chronic hives lasting for at least 6 months and without a known cause may join. The study involves 6 visits over 8 weeks. Approximately 48 participants expected to take part in this study at the Johns Hopkins Asthma and Allergy Clinic. All participants will be treated with the study medication and/or placebo for 8 weeks.

The results of this trial may have a benefit others with Chronic Idiopathic Urticaria who don't respond well to antihistamines by generating experience and data to support the design of a larger, multicenter trial investigating the efficacy of AZD1981 in treating antihistamine refractory CIU.

Detailed description: The investigators propose to use AZD1981 in subjects with chronic idiopathic urticaria (CIU) who are otherwise uncontrolled on first-line, oral antihistamine therapy. The skin lesion pathology in CIU shows a perivascular infiltrate of lymphocytes (both Th2 and Th1), eosinophils, and basophils, and closely resembles an allergen-induced late-phase reaction. Further, murine studies show that the chemoattractant receptor-homologous molecule expressed on Th2 (CRTh2) pathway is important in leukocyte recruitment following allergen challenge of the skin. Our proposed hypothesis is that AZD1981 in CIU will reduce CRTh2-expressing, leukocyte recruitment to the skin and reduce leukocyte activation through CRTh2, thus reducing the signs and symptoms in CIU refractory to control with antihistamines.

Eligibility criteria: Inclusion Criteria:

* Females must be surgically sterile or postmenopausal or using a highly effective form of birth control throughout the duration of the study
* Females must have a negative urine pregnancy test at screening
* Must meet the criteria for Chronic Idiopathic Urticaria (CIU) as defined by itching and hives for \>3 days per week for over 6 weeks with no clear cause
* CIU symptoms must have started at least 6 months prior to starting the study
* Must have moderate to severe CIU, using a standardized survey, despite taking antihistamines

Exclusion Criteria

* Pregnant females or females who plan to become pregnant during the study
* Drug or alcohol abuse within the past 3 years
* Use of any investigational drug with 30 days of the start of the study
* Eczema or other skin conditions associated with itching (besides hives)
* Inability to comply with follow-up procedures
* Use of the following therapies in the past 30 days: hydroxychloroquine, sulfasalazine, dapsone, methotrexate, cyclophosphamide, Intravenous Immunoglobulin (IVIG), plasmapheresis, cyclosporine, oral or systemic steroids, or other monoclonal antibody therapies
* Use of doxepin within the past 2 weeks
* Use of either H2 antihistamines and leukotriene receptor antagonists within 7 days before starting the study (unless already on these medications for Gastroesophageal Reflux Disease (GERD), asthma or allergic rhinitis)
* Inability to take diphenhydramine (Benadryl)
* Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks or interfere with ability to comply with study procedures.

Primary outcomes:
measure: The Change in Diary-based Clinical Symptoms as Measured by the Urticaria Activity Score 7 (UAS7)
timeFrame: 7 Days
Secondary outcomes:
measure: The Number of Participants With Adverse Events
timeFrame: 8 weeks
measure: The Ability of AZD1981 to Inhibit Prostaglandin D2 (PGD2)-Induced Eosinophil Shape
timeFrame: Baseline, End of treatment, end of washout
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Asthma and Allergy Center
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Sarbjit S Saini, MD
role: PRINCIPAL_INVESTIGATOR
References: