Trial Outcomes & Findings for Anti-Inflammatory Agent in Sinusitis (NCT NCT02874144)

NCT ID: NCT02874144

Last Updated: 2022-05-25

Results Overview

Measure Description: Measurement of Primary outcome- 0-4 scale in each nostril, total is 8. The total polyp score is the sum of the right and left nasal polyp score. Maximum is 8, minimum is 0. Higher score indicates worse disease. 0 =No polyps 1=Small polyps in the middle meatus not reaching below the inferior border of the middle turbinate 2=Polyps reaching the lower border of the middle turbinate or polyp medial to the middle turbinate 3 = Large polyps reaching the lower border of the inferior turbinate 4 =Large polyps causing complete obstruction. The primary outcome measured change in polyp size and secondary outcomes included change in radiographic severity of sinus disease, quality of life, and nasal symptoms as measured by Sino Nasal Outcome Test-22 (SNOT-22) and sense of smell by Brief Smell Identification Test (B-SIT) at 12 weeks in the AZD1981 group vs. the placebo. These were done at the baseline visit and the Week 12 visit.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 43 participants
• Primary outcome timeframe: Baseline and Week 12
• Results posted on: 2022-05-25

Participant Flow

Participant milestones

Measure	AZ Compound 40 mg 12 weeks TID po AZ compound: 40 mg three times daily po for 12 weeks Collection of Biological Specimens: collection of biomarkers for analysis of nasal disease Intranasal corticosteroid: QD Nasal Spray	Placebo 40 mg 12 weeks TID po Collection of Biological Specimens: collection of biomarkers for analysis of nasal disease Intranasal corticosteroid: QD Nasal Spray Placebo: looks like AZ compound, made by same company, double blind. 40 mg three times daily po for 12 weeks
Overall Study STARTED	22	21
Overall Study COMPLETED	19	16
Overall Study NOT COMPLETED	3	5

Reasons for withdrawal

Measure	AZ Compound 40 mg 12 weeks TID po AZ compound: 40 mg three times daily po for 12 weeks Collection of Biological Specimens: collection of biomarkers for analysis of nasal disease Intranasal corticosteroid: QD Nasal Spray	Placebo 40 mg 12 weeks TID po Collection of Biological Specimens: collection of biomarkers for analysis of nasal disease Intranasal corticosteroid: QD Nasal Spray Placebo: looks like AZ compound, made by same company, double blind. 40 mg three times daily po for 12 weeks
Overall Study Lost to Follow-up	3	5

Baseline Characteristics

Anti-Inflammatory Agent in Sinusitis

Baseline characteristics by cohort

Measure	AZD + INCS n=22 Participants AZD1981 40 mg 3 times a day orally, added to 2 sprays daily of intranasal corticosteroid (INCS) spray for 12 weeks.	PLACEBO + INCS n=21 Participants Placebo 3 times a day orally added to 2 sprays daily of intranasal corticosteroid (INCS) spray for 12 weeks.	Total n=43 Participants Total of all reporting groups
Age, Continuous	45 years STANDARD_DEVIATION 13 • n=5 Participants	47 years STANDARD_DEVIATION 12 • n=7 Participants	46 years STANDARD_DEVIATION 13 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	13 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	8 Participants n=7 Participants	22 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) White	16 Participants n=5 Participants	14 Participants n=7 Participants	30 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: The primary outcome was the mean change from baseline to 12 weeks in the size of nasal polyps as measured by the total polyp score in the AZD1981 treated group compared to the placebo-treated group.

Measure Description:

Measurement of Primary outcome- 0-4 scale in each nostril, total is 8. The total polyp score is the sum of the right and left nasal polyp score. Maximum is 8, minimum is 0. Higher score indicates worse disease. 0 =No polyps 1=Small polyps in the middle meatus not reaching below the inferior border of the middle turbinate 2=Polyps reaching the lower border of the middle turbinate or polyp medial to the middle turbinate 3 = Large polyps reaching the lower border of the inferior turbinate 4 =Large polyps causing complete obstruction.

The primary outcome measured change in polyp size and secondary outcomes included change in radiographic severity of sinus disease, quality of life, and nasal symptoms as measured by Sino Nasal Outcome Test-22 (SNOT-22) and sense of smell by Brief Smell Identification Test (B-SIT) at 12 weeks in the AZD1981 group vs. the placebo. These were done at the baseline visit and the Week 12 visit.

Outcome measures

Measure	AZD + INCS n=22 Participants AZD1981 40 mg three times a day , added to 2 sprays daily of intranasal corticosteroid (INCS) spray for 12 weeks.	PLACEBO + INCS n=21 Participants Matched Placebo (1:1 randomization) three times a day added to 2 sprays daily of intranasal corticosteroid (INCS) spray for 12 weeks.
TOTAL POLYP SCORE (TPS)	4.67 units on a scale Standard Error 0.38	5.24 units on a scale Standard Error 0.36

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: The secondary outcome was the mean change in Lund-Mackay scores of sinus CT scans from baseline to 12 weeks in the AZD1981 treated group compared to the placebo-treated group.

Measurement of secondary outcome: sinus CT scan scores by Lund-Mckay scores. We measured sinus radiographic severity with Lund-Mackay scores of 0 to 24. 0 was the least severe and 24 was the most severe. This secondary outcomes included change in radiographic severity of sinus disease, as measured by sinus CT scan scores at baseline and 12 weeks in the AZD1981 group vs. the placebo group.

Outcome measures

Measure	AZD + INCS n=22 Participants AZD1981 40 mg three times a day , added to 2 sprays daily of intranasal corticosteroid (INCS) spray for 12 weeks.	PLACEBO + INCS n=21 Participants Matched Placebo (1:1 randomization) three times a day added to 2 sprays daily of intranasal corticosteroid (INCS) spray for 12 weeks.
Sinus CT Scan Scores by Lund-Mackay Scores Visit 1 (Baseline)	17.44 units on a scale Standard Error 1.38	15.53 units on a scale Standard Error 1.43
Sinus CT Scan Scores by Lund-Mackay Scores Visit 5 (12 weeks)	18.25 units on a scale Standard Error 1.1	16.33 units on a scale Standard Error 1.14

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: The secondary outcome was the mean change from baseline to 12 weeks of BSIT scores in the AZD1981 treated group compared to the placebo-treated group.

Measurement of secondary outcome- BSIT (brief smell identification test) is a 12-item test measuring sense of smell. This is a multiple choice test with one correct answer out of four possible answer choices. This test features distinct types of smells. Minimum score: 0/12, which indicates that none of the correct answers were chosen on the 12-item test. Maximum score: 12/12, which indicates that all of the correct answers were chosen on the 12-item test. The higher the score, the better the outcome. Only one out of the four possible answer choices for each multiple choice question is correct. There are no subscales.

This secondary outcome measures sense of smell by Brief Smell Identification Test (B-SIT) at baseline (visit 1) and 12 weeks (visit 5) in the AZD1981 group vs. the placebo group.

Outcome measures

Measure	AZD + INCS n=22 Participants AZD1981 40 mg three times a day , added to 2 sprays daily of intranasal corticosteroid (INCS) spray for 12 weeks.	PLACEBO + INCS n=21 Participants Matched Placebo (1:1 randomization) three times a day added to 2 sprays daily of intranasal corticosteroid (INCS) spray for 12 weeks.
BSIT (Brief Smell Identification Test) Visit 1 (Baseline)	5.75 units on a scale Standard Error 0.81	5.20 units on a scale Standard Error 0.88
BSIT (Brief Smell Identification Test) Visit 5 (12 weeks)	6.92 units on a scale Standard Error 1.12	5.80 units on a scale Standard Error 1.22

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: This secondary outcome was the mean change from baseline to 12 weeks in sinonasal symptoms detailed in the SNOT-22 as measured by the total polyp score in the AZD1981 treated group compared to the placebo-treated group.

Measurement of secondary outcome- the SNOT-22 test contains 22 items regarding patient-reported outcomes of sino-nasal symptom severity on a 0-5 scale for each item. 0 is no problem and 5 is problem as bad as it can be, so higher values represent a worse outcome than lower values. The subscale is 0 - 5 of each of the 22 items and the total score is the sum of the subscales of all 22 items. The minimum total score is 0/110. The maximum total score is 110/110.

This secondary outcome measured change in patient-reported outcomes of nasal symptoms as measured by Sino Nasal Outcome Test-22 (SNOT-22) over 12 weeks in the AZD1981 group vs. the placebo group.

Outcome measures

Measure	AZD + INCS n=22 Participants AZD1981 40 mg three times a day , added to 2 sprays daily of intranasal corticosteroid (INCS) spray for 12 weeks.	PLACEBO + INCS n=21 Participants Matched Placebo (1:1 randomization) three times a day added to 2 sprays daily of intranasal corticosteroid (INCS) spray for 12 weeks.
SNOT-22 (Sino-Nasal Outcome Test-22) Score Visit 1 (baseline)	33.73 units on a scale Standard Error 5.17	40.41 units on a scale Standard Error 5.01
SNOT-22 (Sino-Nasal Outcome Test-22) Score Visit 5 (12 weeks)	26.07 units on a scale Standard Error 4.94	36.13 units on a scale Standard Error 4.78

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: The secondary outcome was the mean change from baseline (visit 1) to 12 weeks (visit 5) of the VAS scores in the AZD1981 treated group compared to the placebo-treated group.

Measurement of secondary outcome- 0 to 10 scale bilaterally that measures how subjective sinus symptom severity, with 0 being the least troublesome to 10 being the most troublesome over 12 weeks in the AZD1981 group vs. the placebo group.

Outcome measures

Measure	AZD + INCS n=22 Participants AZD1981 40 mg three times a day , added to 2 sprays daily of intranasal corticosteroid (INCS) spray for 12 weeks.	PLACEBO + INCS n=21 Participants Matched Placebo (1:1 randomization) three times a day added to 2 sprays daily of intranasal corticosteroid (INCS) spray for 12 weeks.
Visual Analog Scale (VAS) Visit 1	5.57 units on a scale Standard Error 2.59	5.70 units on a scale Standard Error 2.60
Visual Analog Scale (VAS) Visit 5	4.75 units on a scale Standard Error 2.66	4.74 units on a scale Standard Error 2.66

Adverse Events

AZ+INCS

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo + INCS

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	AZ+INCS n=22 participants at risk AZD1981 40 mg three times a day , added to 2 sprays daily of intranasal corticosteroid (INCS) spray for 12 weeks.	Placebo + INCS n=21 participants at risk Matched Placebo (1:1 randomization) three times a day added to 2 sprays daily of intranasal corticosteroid (INCS) spray for 12 weeks
Gastrointestinal disorders Diverticulitis	0.00% 0/22 • Adverse Events were assessed every 2 weeks for the first month, then every 4 weeks for 12 weeks and during a 4 week washout period, an average of 5 months. AE and SAE information was collected under GCP and specific IRB guidelines. All patients were assessed for adverse effects every 2 weeks for the first month and then every 4 weeks during the 12-week study and during a 4 week washout period by means of adverse events reports, physical examination, and laboratory tests (complete blood counts and renal and hepatic chemistries).	4.8% 1/21 • Number of events 1 • Adverse Events were assessed every 2 weeks for the first month, then every 4 weeks for 12 weeks and during a 4 week washout period, an average of 5 months. AE and SAE information was collected under GCP and specific IRB guidelines. All patients were assessed for adverse effects every 2 weeks for the first month and then every 4 weeks during the 12-week study and during a 4 week washout period by means of adverse events reports, physical examination, and laboratory tests (complete blood counts and renal and hepatic chemistries).
Respiratory, thoracic and mediastinal disorders Hypersensitivity	4.5% 1/22 • Number of events 1 • Adverse Events were assessed every 2 weeks for the first month, then every 4 weeks for 12 weeks and during a 4 week washout period, an average of 5 months. AE and SAE information was collected under GCP and specific IRB guidelines. All patients were assessed for adverse effects every 2 weeks for the first month and then every 4 weeks during the 12-week study and during a 4 week washout period by means of adverse events reports, physical examination, and laboratory tests (complete blood counts and renal and hepatic chemistries).	0.00% 0/21 • Adverse Events were assessed every 2 weeks for the first month, then every 4 weeks for 12 weeks and during a 4 week washout period, an average of 5 months. AE and SAE information was collected under GCP and specific IRB guidelines. All patients were assessed for adverse effects every 2 weeks for the first month and then every 4 weeks during the 12-week study and during a 4 week washout period by means of adverse events reports, physical examination, and laboratory tests (complete blood counts and renal and hepatic chemistries).

Other adverse events

Measure	AZ+INCS n=22 participants at risk AZD1981 40 mg three times a day , added to 2 sprays daily of intranasal corticosteroid (INCS) spray for 12 weeks.	Placebo + INCS n=21 participants at risk Matched Placebo (1:1 randomization) three times a day added to 2 sprays daily of intranasal corticosteroid (INCS) spray for 12 weeks
Respiratory, thoracic and mediastinal disorders Rash	4.5% 1/22 • Number of events 1 • Adverse Events were assessed every 2 weeks for the first month, then every 4 weeks for 12 weeks and during a 4 week washout period, an average of 5 months. AE and SAE information was collected under GCP and specific IRB guidelines. All patients were assessed for adverse effects every 2 weeks for the first month and then every 4 weeks during the 12-week study and during a 4 week washout period by means of adverse events reports, physical examination, and laboratory tests (complete blood counts and renal and hepatic chemistries).	0.00% 0/21 • Adverse Events were assessed every 2 weeks for the first month, then every 4 weeks for 12 weeks and during a 4 week washout period, an average of 5 months. AE and SAE information was collected under GCP and specific IRB guidelines. All patients were assessed for adverse effects every 2 weeks for the first month and then every 4 weeks during the 12-week study and during a 4 week washout period by means of adverse events reports, physical examination, and laboratory tests (complete blood counts and renal and hepatic chemistries).

Additional Information

Anju Peters

Northwestern

Phone: 3126950513

Email: anju.peters@northwestern.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place