Trial Outcomes & Findings for Benralizumab Effect on Severe Chronic Rhinosinusitis With Eosinophilic Polyposis (NCT NCT03450083)

Results Overview

Change in endoscopic nasal polyp score after 6 months of treatment. Nasal Polyp Score (NPS): the change in mean score from Screen visit (Week 5) bilateral endoscopic nasal polyp score as compared to score at end of treatment (Week 25). Higher scores indicate increase in number of polyps and/or polyp size. The score is the sum of the right and left nostril scores, as evaluated by nasal endoscopy. NPS score key: 0 = No visible polyps; 1 = Small amount of polypoid disease confined within the middle meatus; 2 = Multiple polyps occupying the middle meatus; 3 = Polyps extending beyond the middle meatus; 4 = Polyps completely obstructing the nasal cavity. Reported data is a difference in the NPS between Week 25 and Week 5.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

33 participants

Primary outcome timeframe

Week 5 and Week 25

Results posted on

2021-02-11

Participant Flow

33 participants signed Informed Consent; 2 participants did not meet inclusion criteria and 7 participants decided to not continue with study activities prior to receiving any intervention.

Participant milestones

Participant milestones
Measure	Benralizumab Treatment Group Benralizumab Active treatment group delivered subcutaneously Benralizumab: 30mg Benralizumab will be delivered subcutaneously	Placebo Group Placebo treatment group delivered subcutaneously Placebo: Subcutaneous placebo injection
Overall Study STARTED	12	12
Overall Study COMPLETED	12	12
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Benralizumab Effect on Severe Chronic Rhinosinusitis With Eosinophilic Polyposis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Benralizumab Treatment Group n=12 Participants Benralizumab Active treatment group delivered subcutaneously Benralizumab: 30mg Benralizumab will be delivered subcutaneously	Placebo Group n=12 Participants Placebo treatment group delivered subcutaneously Placebo: Subcutaneous placebo injection	Total n=24 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=93 Participants	11 Participants n=4 Participants	22 Participants n=27 Participants
Age, Categorical >=65 years	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Age, Continuous	49.8 years n=93 Participants	50.8 years n=4 Participants	50.3 years n=27 Participants
Sex: Female, Male Female	5 Participants n=93 Participants	5 Participants n=4 Participants	10 Participants n=27 Participants
Sex: Female, Male Male	7 Participants n=93 Participants	7 Participants n=4 Participants	14 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=93 Participants	12 Participants n=4 Participants	24 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	12 Participants n=93 Participants	12 Participants n=4 Participants	24 Participants n=27 Participants

PRIMARY outcome

Timeframe: Week 5 and Week 25

Change in endoscopic nasal polyp score after 6 months of treatment. Nasal Polyp Score (NPS): the change in mean score from Screen visit (Week 5) bilateral endoscopic nasal polyp score as compared to score at end of treatment (Week 25). Higher scores indicate increase in number of polyps and/or polyp size. The score is the sum of the right and left nostril scores, as evaluated by nasal endoscopy. NPS score key: 0 = No visible polyps; 1 = Small amount of polypoid disease confined within the middle meatus; 2 = Multiple polyps occupying the middle meatus; 3 = Polyps extending beyond the middle meatus; 4 = Polyps completely obstructing the nasal cavity. Reported data is a difference in the NPS between Week 25 and Week 5.

Outcome measures

Outcome measures
Measure	Benralizumab Treatment Group n=12 Participants Benralizumab Active treatment group delivered subcutaneously Benralizumab: 30mg Benralizumab will be delivered subcutaneously	Placebo Group n=12 Participants Placebo treatment group delivered subcutaneously Placebo: Subcutaneous placebo injection
Change in Nasal Polyp Score	.9 score on a scale Interval 0.0 to 3.0	.3 score on a scale Interval -1.0 to 2.0

SECONDARY outcome

Timeframe: Week 5 and Week 25

Computed Tomography (CT) scan of the sinus was performed at screening (Week 5) and then again at the end of treatment (Week 25). Sinus CT images were obtained to determine the Lund Mackay Score (LMS), a widely used method for radiologic staging of nasal polyposis. The mean change in the LMS was determined by comparing the scores from Week 5 to Week 25. Each sinus group is graded between 0 and 2 (0: no abnormality; 1: partial opacification; 2: total opacification). The ostiomeatal complex is scored as "0" not obstructed) or "2" (obstructed). Overall score range of 0-24. Higher scores indicate progression of nasal polyposis disease. Reported data is a difference in the LMS between Week 25 and Week 5.

Outcome measures

Outcome measures
Measure	Benralizumab Treatment Group n=12 Participants Benralizumab Active treatment group delivered subcutaneously Benralizumab: 30mg Benralizumab will be delivered subcutaneously	Placebo Group n=12 Participants Placebo treatment group delivered subcutaneously Placebo: Subcutaneous placebo injection
Change in Nasal Polyp Size as Assessed by the Lund Mackay Score	-4.2 score on a scale Standard Error 1.1	-1.6 score on a scale Standard Error 1.2

SECONDARY outcome

Timeframe: Treatment Week 0 and Week 20

The Sino-nasal Outcome Test (SNOT-22) is a condition-specific health-related quality of life assessment that captures patient-reported physical problems, functional limitations, and emotional consequences of sinonasal conditions for the 2 weeks prior to completing the test. Participants completed the SNOT-22 at treatment Week 0 and at Treatment Week 20. Patients rated their symptom severity and symptom impact over the previous 2 weeks using a 6-point scale (0- No Problem to 5- Problem as bad as it can be). The total score is the sum of individual item scores and has a range from 0 to 110. Higher scores indicate more severe symptoms. Outcome measure data shows change in SNOT-22 scores between treatment Week 20 and Week 0.

Outcome measures

Outcome measures
Measure	Benralizumab Treatment Group n=12 Participants Benralizumab Active treatment group delivered subcutaneously Benralizumab: 30mg Benralizumab will be delivered subcutaneously	Placebo Group n=12 Participants Placebo treatment group delivered subcutaneously Placebo: Subcutaneous placebo injection
Change in Symptom Severity Score as Assessed by the Sino-nasal Outcome Test	-19.2 score on a scale Standard Deviation 2.6	-14.6 score on a scale Standard Deviation 20.1

SECONDARY outcome

Timeframe: Week 5 and Week 25

The University of Pennsylvania Smell Identification Test (UPSIT) is a quantitative test of olfactory function that uses microencapsulated odorants that are released by scratching standardized odor-impregnated test booklets. Four booklets with 10 questions in each booklet on odor identification. Patients were asked to identify the odor by scratching the test area then selecting their answer using multiple-choice format that lists 4 different possible answers for each question. The mean change in the UPSIT was determined by comparing the score from Week 5 to the score in Week 25. The test is a forced-choice test meaning the patient is required to mark one of the four answers even if a smell is not perceived. Scores are based on number of correctly identified odors (score range 0 to 40). Higher scores indicate subject's ability to correctly identify odors. Reported data is a difference in the UPSIT score between Week 25 and Week 5.

Outcome measures

Outcome measures
Measure	Benralizumab Treatment Group n=12 Participants Benralizumab Active treatment group delivered subcutaneously Benralizumab: 30mg Benralizumab will be delivered subcutaneously	Placebo Group n=12 Participants Placebo treatment group delivered subcutaneously Placebo: Subcutaneous placebo injection
Change in The University of Pennsylvania Smell Identification Test Score	6.6 score on a scale Standard Error 2.2	4.3 score on a scale Standard Error 2.5

SECONDARY outcome

Timeframe: Assessed at Treatment Week 0 and Week 20

Complete Blood Count (CBC) to determine change in absolute eosinophil count. Normal Range 30-300 cells/uL.

Outcome measures

Outcome measures
Measure	Benralizumab Treatment Group n=12 Participants Benralizumab Active treatment group delivered subcutaneously Benralizumab: 30mg Benralizumab will be delivered subcutaneously	Placebo Group n=12 Participants Placebo treatment group delivered subcutaneously Placebo: Subcutaneous placebo injection
Change in Absolute Eosinophil Count	678 cells/uL Standard Error 119	196.7 cells/uL Standard Error 171

SECONDARY outcome

Timeframe: 20 weeks

Use of Prednisone as a rescue medication during the treatment phase (week 0 through week 20) was measured in total milligrams (mg) that were taken by participant.

Outcome measures

Outcome measures
Measure	Benralizumab Treatment Group n=12 Participants Benralizumab Active treatment group delivered subcutaneously Benralizumab: 30mg Benralizumab will be delivered subcutaneously	Placebo Group n=12 Participants Placebo treatment group delivered subcutaneously Placebo: Subcutaneous placebo injection
Utilization of Prednisone as a Rescue Medication	302.5 mg Standard Deviation 407.77	297.5 mg Standard Deviation 294.12

SECONDARY outcome

Timeframe: 24 weeks

Population: Time to nasal polyp surgery post treatment was not assessed and no data was collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 29 weeks

Number of participants who dropped out monitored continuously throughout the study up to 29 weeks.

Outcome measures

Outcome measures
Measure	Benralizumab Treatment Group n=12 Participants Benralizumab Active treatment group delivered subcutaneously Benralizumab: 30mg Benralizumab will be delivered subcutaneously	Placebo Group n=12 Participants Placebo treatment group delivered subcutaneously Placebo: Subcutaneous placebo injection
Number of Participants Who Dropped Out	0 Participants	0 Participants

Adverse Events

Benralizumab Treatment Group

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo Group

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Benralizumab Treatment Group n=12 participants at risk Benralizumab Active treatment group delivered subcutaneously Benralizumab: 30mg Benralizumab will be delivered subcutaneously	Placebo Group n=12 participants at risk Placebo treatment group delivered subcutaneously Placebo: Subcutaneous placebo injection
General disorders Upper Respiratory Infection (URI)	8.3% 1/12 • Number of events 1 • Approximately 9 months (from date of signed consent to 30 days after completion of therapy).	16.7% 2/12 • Number of events 2 • Approximately 9 months (from date of signed consent to 30 days after completion of therapy).

Additional Information

Jody Tversky, MD

Johns Hopkins University School of Medicine

Phone: 410-550-8017

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place