Trial Outcomes & Findings for Efficacy and Safety of Chemoattractant Receptor-homologous Molecule Expressed on T Helper Type 2 (CRTh2) Antagonist AZD1981 in Chronic Idiopathic Urticaria (CIU) Antihistamines (NCT NCT02031679)
NCT ID: NCT02031679
Last Updated: 2017-07-12
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
38 participants
Primary outcome timeframe
7 Days
Results posted on
2017-07-12
Participant Flow
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).
Participant milestones
| Measure |
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.
AZD1981: AZD1981 is an oral, potent, selective, reversible antagonist of CRTh2 (Chemoattractant Receptor Homologous Molecule expressed on Th2 cells).
|
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.
Placebo: Sugar pill manufactured to mimic AZD1981 10 mg tablet
|
|---|---|---|
|
Overall Study
STARTED
|
14
|
14
|
|
Overall Study
COMPLETED
|
14
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
| Measure |
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.
AZD1981: AZD1981 is an oral, potent, selective, reversible antagonist of CRTh2 (Chemoattractant Receptor Homologous Molecule expressed on Th2 cells).
|
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.
Placebo: Sugar pill manufactured to mimic AZD1981 10 mg tablet
|
|---|---|---|
|
Overall Study
Protocol Violation
|
0
|
1
|
|
Overall Study
Lack of Efficacy
|
0
|
1
|
Baseline Characteristics
There was no significant difference in age between study groups.
Baseline characteristics by cohort
| Measure |
AZD1981
n=14 Participants
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).
|
Placebo
n=12 Participants
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
n=26 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
14 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
26 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Continuous
|
41.85 years
n=99 Participants • There was no significant difference in age between study groups.
|
45.17 years
n=107 Participants • There was no significant difference in age between study groups.
|
43.38 years
n=206 Participants • There was no significant difference in age between study groups.
|
|
Sex: Female, Male
Female
|
10 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
20 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
14 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
26 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
14 participants
n=99 Participants
|
12 participants
n=107 Participants
|
26 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 7 DaysPopulation: One placebo subject had diary data compromised by device malfunction so only full data for 11 subjects were analyzed
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.
Outcome measures
| Measure |
AZD1981
n=12 Participants
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).
|
Placebo
n=11 Participants
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
|
|---|---|---|
|
The Change in Diary-based Clinical Symptoms as Measured by the Urticaria Activity Score 7 (UAS7)
End of Treatment
|
18.83 UAS7 Scores
Standard Error 3.779
|
18 UAS7 Scores
Standard Error 3.614
|
|
The Change in Diary-based Clinical Symptoms as Measured by the Urticaria Activity Score 7 (UAS7)
End of Washout
|
15.79 UAS7 Scores
Standard Error 3.726
|
19 UAS7 Scores
Standard Error 3.465
|
|
The Change in Diary-based Clinical Symptoms as Measured by the Urticaria Activity Score 7 (UAS7)
Baseline
|
20.46 UAS7 Scores
Standard Error 3.655
|
24.59 UAS7 Scores
Standard Error 3.463
|
SECONDARY outcome
Timeframe: 8 weeksThe 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.
Outcome measures
| Measure |
AZD1981
n=14 Participants
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).
|
Placebo
n=12 Participants
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
|
|---|---|---|
|
The Number of Participants With Adverse Events
|
9 participants with adverse events
|
8 participants with adverse events
|
SECONDARY outcome
Timeframe: Baseline, End of treatment, end of washoutPopulation: Insufficient samples were obtained for one active and 2 placebo patients.
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.
Outcome measures
| Measure |
AZD1981
n=13 Participants
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).
|
Placebo
n=10 Participants
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
|
|---|---|---|
|
The Ability of AZD1981 to Inhibit Prostaglandin D2 (PGD2)-Induced Eosinophil Shape
Baseline
|
1521.317 Mean fluorescence units area under curve
Standard Deviation 138.146
|
1472.867 Mean fluorescence units area under curve
Standard Deviation 184.401
|
|
The Ability of AZD1981 to Inhibit Prostaglandin D2 (PGD2)-Induced Eosinophil Shape
End of Treatment
|
1435.540 Mean fluorescence units area under curve
Standard Deviation 137.752
|
1456.602 Mean fluorescence units area under curve
Standard Deviation 157.485
|
|
The Ability of AZD1981 to Inhibit Prostaglandin D2 (PGD2)-Induced Eosinophil Shape
End of Washout
|
1508.367 Mean fluorescence units area under curve
Standard Deviation 116.085
|
1406.221 Mean fluorescence units area under curve
Standard Deviation 108.539
|
Adverse Events
AZD1981
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
AZD1981
n=14 participants at risk
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).
|
Placebo
n=12 participants at risk
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
|
|---|---|---|
|
Nervous system disorders
Headache
|
0.00%
0/14
|
16.7%
2/12 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal
|
21.4%
3/14 • Number of events 3
|
8.3%
1/12 • Number of events 1
|
|
Infections and infestations
Infection
|
35.7%
5/14 • Number of events 5
|
41.7%
5/12 • Number of events 5
|
|
Psychiatric disorders
Sleep impairment
|
7.1%
1/14 • Number of events 1
|
8.3%
1/12 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory disorders (non-infectious)
|
0.00%
0/14
|
0.00%
0/12
|
|
Gastrointestinal disorders
Gastrointestinal disorders
|
35.7%
5/14 • Number of events 5
|
16.7%
2/12 • Number of events 2
|
|
Blood and lymphatic system disorders
Blood disorders
|
0.00%
0/14
|
0.00%
0/12
|
|
Eye disorders
Eye and vision disorders
|
0.00%
0/14
|
8.3%
1/12 • Number of events 1
|
|
Cardiac disorders
Cardiovascular disorders
|
7.1%
1/14 • Number of events 1
|
8.3%
1/12 • Number of events 1
|
|
Renal and urinary disorders
Renal disorders
|
0.00%
0/14
|
0.00%
0/12
|
|
Reproductive system and breast disorders
Reproductive disorders
|
0.00%
0/14
|
0.00%
0/12
|
|
Skin and subcutaneous tissue disorders
Skin or hair disorders
|
0.00%
0/14
|
16.7%
2/12 • Number of events 2
|
|
Immune system disorders
Immunologic disorders
|
0.00%
0/14
|
0.00%
0/12
|
Additional Information
Dr. Eric Oliver
Johns Hopkins University School of Medicine
Phone: 410-550-2300
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place