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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Chronic Idiopathic Urticaria
Interventions Drug: AZD1981
Drug: Placebo
Enrollment 38
Recruitment Details  
Pre-assignment Details This study involved a 1-week screening period and a 2-week single-blind placebo run-in before randomization to active or placebo treatment. 10/38 enrolled subjects were excluded based on low disease activity (n=5), inability to remain solely on daily H1 antihistamine (n=4), and noncompliance (n=1).
Arm/Group Title AZD1981 Placebo
Hide Arm/Group Description

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.

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

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.

Placebo: Sugar pill manufactured to mimic AZD1981 10 mg tablet

Period Title: Overall Study
Started 14 14
Completed 14 12
Not Completed 0 2
Reason Not Completed
Protocol Violation             0             1
Lack of Efficacy             0             1
Arm/Group Title AZD1981 Placebo Total
Hide Arm/Group Description

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.

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

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.

Placebo: Sugar pill manufactured to mimic AZD1981 10 mg tablet

Total of all reporting groups
Overall Number of Baseline Participants 14 12 26
Hide Baseline Analysis Population Description
Participants were randomized to AZD1981 or placebo at the end of placebo-run in, not at baseline. Values below reflect randomized subjects.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 12 participants 26 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
14
 100.0%
12
 100.0%
26
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous   [1] 
Median (Full Range)
Unit of measure:  Years
Number Analyzed 14 participants 12 participants 26 participants
41.85
(23 to 65)
45.17
(23 to 64)
43.38
(23 to 65)
[1]
Measure Analysis Population Description: There was no significant difference in age between study groups.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 12 participants 26 participants
Female
10
  71.4%
10
  83.3%
20
  76.9%
Male
4
  28.6%
2
  16.7%
6
  23.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 12 participants 26 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
14
 100.0%
12
 100.0%
26
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 12 participants 26 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
3
  21.4%
2
  16.7%
5
  19.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   8.3%
1
   3.8%
Black or African American
4
  28.6%
4
  33.3%
8
  30.8%
White
6
  42.9%
4
  33.3%
10
  38.5%
More than one race
1
   7.1%
1
   8.3%
2
   7.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 14 participants 12 participants 26 participants
14 12 26
1.Primary Outcome
Title The Change in Diary-based Clinical Symptoms as Measured by the Urticaria Activity Score 7 (UAS7)
Hide Description 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.
Time Frame 7 Days
Hide Outcome Measure Data
Hide Analysis Population Description
One placebo subject had diary data compromised by device malfunction so only full data for 11 subjects were analyzed
Arm/Group Title AZD1981 Placebo
Hide Arm/Group Description:

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.

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

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.

Placebo: Sugar pill manufactured to mimic AZD1981 10 mg tablet

Overall Number of Participants Analyzed 12 11
Mean (Standard Error)
Unit of Measure: UAS7 Scores
Baseline 20.46  (3.655) 24.59  (3.463)
End of Treatment 18.83  (3.779) 18  (3.614)
End of Washout 15.79  (3.726) 19  (3.465)
2.Secondary Outcome
Title The Number of Participants With Adverse Events
Hide Description 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.
Time Frame 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AZD1981 Placebo
Hide Arm/Group Description:

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.

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

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.

Placebo: Sugar pill manufactured to mimic AZD1981 10 mg tablet

Overall Number of Participants Analyzed 14 12
Measure Type: Number
Unit of Measure: participants with adverse events
9 8
3.Secondary Outcome
Title The Ability of AZD1981 to Inhibit Prostaglandin D2 (PGD2)-Induced Eosinophil Shape
Hide Description 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.
Time Frame Baseline, End of treatment, end of washout
Hide Outcome Measure Data
Hide Analysis Population Description
Insufficient samples were obtained for one active and 2 placebo patients.
Arm/Group Title AZD1981 Placebo
Hide Arm/Group Description:

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.

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

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.

Placebo: Sugar pill manufactured to mimic AZD1981 10 mg tablet

Overall Number of Participants Analyzed 13 10
Mean (Standard Deviation)
Unit of Measure: Mean fluorescence units area under curve
Baseline 1521.317  (138.146) 1472.867  (184.401)
End of Treatment 1435.540  (137.752) 1456.602  (157.485)
End of Washout 1508.367  (116.085) 1406.221  (108.539)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title AZD1981 Placebo
Hide Arm/Group Description

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.

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

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.

Placebo: Sugar pill manufactured to mimic AZD1981 10 mg tablet

All-Cause Mortality
AZD1981 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/14 (0.00%)      0/12 (0.00%)    
Hide Serious Adverse Events
AZD1981 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/14 (0.00%)      0/12 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
AZD1981 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/14 (64.29%)      8/12 (66.67%)    
Blood and lymphatic system disorders     
Blood disorders *  0/14 (0.00%)  0 0/12 (0.00%)  0
Cardiac disorders     
Cardiovascular disorders *  1/14 (7.14%)  1 1/12 (8.33%)  1
Eye disorders     
Eye and vision disorders *  0/14 (0.00%)  0 1/12 (8.33%)  1
Gastrointestinal disorders     
Gastrointestinal disorders *  5/14 (35.71%)  5 2/12 (16.67%)  2
Immune system disorders     
Immunologic disorders *  0/14 (0.00%)  0 0/12 (0.00%)  0
Infections and infestations     
Infection *  5/14 (35.71%)  5 5/12 (41.67%)  5
Musculoskeletal and connective tissue disorders     
Musculoskeletal *  3/14 (21.43%)  3 1/12 (8.33%)  1
Nervous system disorders     
Headache *  0/14 (0.00%)  0 2/12 (16.67%)  2
Psychiatric disorders     
Sleep impairment *  1/14 (7.14%)  1 1/12 (8.33%)  1
Renal and urinary disorders     
Renal disorders *  0/14 (0.00%)  0 0/12 (0.00%)  0
Reproductive system and breast disorders     
Reproductive disorders *  0/14 (0.00%)  0 0/12 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Respiratory disorders (non-infectious) *  0/14 (0.00%)  0 0/12 (0.00%)  0
Skin and subcutaneous tissue disorders     
Skin or hair disorders *  0/14 (0.00%)  0 2/12 (16.67%)  2
*
Indicates events were collected by non-systematic assessment
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.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Eric Oliver
Organization: Johns Hopkins University School of Medicine
Phone: 410-550-2300
EMail: eolive15@jhmi.edu
Layout table for additonal information
Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT02031679    
Other Study ID Numbers: NA_00089252
First Submitted: January 7, 2014
First Posted: January 9, 2014
Results First Submitted: April 4, 2017
Results First Posted: July 12, 2017
Last Update Posted: July 12, 2017