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

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ClinicalTrials.gov Identifier: NCT02031679
Recruitment Status : Completed
First Posted : January 9, 2014
Results First Posted : July 12, 2017
Last Update Posted : July 12, 2017
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Johns Hopkins University

Tracking Information
First Submitted Date  ICMJE January 7, 2014
First Posted Date  ICMJE January 9, 2014
Results First Submitted Date  ICMJE April 4, 2017
Results First Posted Date  ICMJE July 12, 2017
Last Update Posted Date July 12, 2017
Actual Study Start Date  ICMJE January 2014
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 13, 2017)
The Change in Diary-based Clinical Symptoms as Measured by the Urticaria Activity Score 7 (UAS7) [ Time Frame: 7 Days ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 7, 2014)
The Change in Diary-based Clinical Symptoms as Measured by the Urticaria Activity Score 7 (UAS7) [ Time Frame: 21-28 Days ]
The UAS score, which is the sum of pruritus and hives, will be used to calculate the UAS7. The UAS7 is a sum of the daily average (average of a.m. and p.m.) for 7 days
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 13, 2017)
  • The Number of Participants With Adverse Events [ Time Frame: 8 weeks ]
    The safety of AZD1981 will be assessed using the following outcome measures: incidence and severity of treatment-emergent adverse events and serious adverse events, clinical laboratory measures, and vital signs. In particular we will measure CBC's with differential at baseline and week 4 and liver function tests every 2 weeks based on past trial experience of dose-related toxicity.
  • The Ability of AZD1981 to Inhibit Prostaglandin D2 (PGD2)-Induced Eosinophil Shape [ Time Frame: Baseline, End of treatment, end of washout ]
    The measure of Eosinophil shape change was assessed by cell scatter characteristics using a flow cytometer. Cellular scatter was established with buffer and then several doses of PGD2 stimulation.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 7, 2014)
  • The Number of Participants With Adverse Events [ Time Frame: 8 weeks ]
    The safety of AZD1981 will be assessed using the following outcome measures: incidence and severity of treatment-emergent adverse events and serious adverse events, clinical laboratory measures, and vital signs. In particular we will measure CBC's with differential at baseline and week 4 and liver function tests every 2 weeks based on past trial experience of dose-related toxicity.
  • The ability of AZD1981 to inhibit PGD2-induced Eosinophil shape [ Time Frame: 21-28 days ]
  • The quality of life benefit provided by treatment of refractory CIU with AZD1981 in CIU as assessed by a sleep interference scale and Dermatology Life Quality Index (DLQI) [ Time Frame: 21-28 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: January 7, 2014)
  • Change in circulating leukocyte population numbers that are targeted by CRTh2 inhibition such as blood basophils, eosinophil and lymphocyte counts [ Time Frame: 21-28 days ]
  • The proportion of patients who achieve at least 50% improvement/decrease from baseline in UAS7 [ Time Frame: 21-28 days ]
  • Pruritus-free and hive-free days (based on diary) during treatment period. [ Time Frame: 21-28 days ]
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Chronic Idiopathic Urticaria
Intervention  ICMJE
  • Drug: AZD1981
    AZD1981 is an oral, potent, selective, reversible antagonist of CRTh2 (Chemoattractant Receptor Homologous Molecule expressed on Th2 cells).
    Other Name: Oral CRTh2 antagonist
  • Drug: Placebo
    Sugar pill manufactured to mimic AZD1981 10 mg tablet
Study Arms  ICMJE
  • Experimental: AZD1981

    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.

    Intervention: Drug: AZD1981
  • Placebo Comparator: Placebo

    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.

    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 13, 2017)
38
Original Estimated Enrollment  ICMJE
 (submitted: January 7, 2014)
48
Actual Study Completion Date  ICMJE January 2016
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02031679
Other Study ID Numbers  ICMJE NA_00089252
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Johns Hopkins University
Study Sponsor  ICMJE Johns Hopkins University
Collaborators  ICMJE AstraZeneca
Investigators  ICMJE
Principal Investigator: Sarbjit S Saini, MD Johns Hopkins University
PRS Account Johns Hopkins University
Verification Date June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP