Efficacy and Safety of Chemoattractant Receptor-homologous Molecule Expressed on T Helper Type 2 (CRTh2) Antagonist AZD1981 in Chronic Idiopathic Urticaria (CIU) Antihistamines

NCT02031679 | Completed Phase 2 Results

• 1 other identifier: NA_00089252
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Idiopathic Urticaria

Keywords

Chronic Idiopathic Urticaria

Outcome Measures

Primary Outcomes (1)

• The Change in Diary-based Clinical Symptoms as Measured by the Urticaria Activity Score 7 (UAS7)

  The UAS score, which is the sum of pruritus and hives, will be used to calculate the UAS7. UAS is a validated measure of Chronic Spontaneous Urticaria (CSU) disease activity which scores the intensity of pruritus (0-3, with 0 = no itch and 3 is severe itch) and number of hives (0-3 0 means no hives and 3 means greater than 50 hives) with a maximum value of 6 for a given day. The UAS7 is the sum of the daily average UAS scores (average of a.m. and p.m.) for 7 days with a minimum score of 0 and a maximum value of 42. The UAS7 is a sum of the daily average (average of a.m. and p.m.) for 7 days. The baseline score was established during the second placebo therapy week and compared to the final week of the 4 week active treatment period.

  7 Days

Secondary Outcomes (2)

• The Number of Participants With Adverse Events

  8 weeks

• The Ability of AZD1981 to Inhibit Prostaglandin D2 (PGD2)-Induced Eosinophil Shape

  Baseline, End of treatment, end of washout

Study Arms (2)

AZD1981

EXPERIMENTAL

AZD1981 for oral administration will be available in tablet form. AZD1981 tablets will be provided in 10 mg strengths. The drug will be self-administered by the subject. Subjects will take 4 tablets in the morning, 4 tablets in the afternoon, and 4 tablets in the evening. The tablets should be swallowed whole with a glass of water.

Drug: AZD1981

Placebo

PLACEBO COMPARATOR

The placebo will be available in tablet form. The placebo contains the same ingredients as the AZD1981 with the exception of the active compound. The placebo will be self-administered by the subject. Subjects will take 4 tablets in the morning, 4 tablets in the afternoon, and 4 tablets in the evening. The tablets should be swallowed whole with a glass of water.

Drug: Placebo

Interventions

AZD1981 DRUG

AZD1981 is an oral, potent, selective, reversible antagonist of CRTh2 (Chemoattractant Receptor Homologous Molecule expressed on Th2 cells).

Also known as: Oral CRTh2 antagonist

AZD1981

Placebo DRUG

Sugar pill manufactured to mimic AZD1981 10 mg tablet

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Johns Hopkins University: lead
• AstraZeneca: collaborator

Study Sites (1)

Johns Hopkins Asthma and Allergy Center

Baltimore, Maryland, 21224-6821, United States

Location

MeSH Terms

Conditions

Chronic Urticaria

Interventions

AZD1981

Condition Hierarchy (Ancestors)

Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Among the limitations of this study are the small number of subjects, short duration of therapy and washout periods, and the lack of skin tissue biopsies to correspond with peripheral blood leukocyte findings.

Results Point of Contact

• Title: Dr. Eric Oliver
• Organization: Johns Hopkins University School of Medicine

eolive15@jhmi.edu

410-550-2300

Study Officials

• Sarbjit S Saini, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2014
• First Posted: January 9, 2014
• Study Start: January 1, 2014
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: July 12, 2017
• Results First Posted: July 12, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)