Trial Outcomes & Findings for Etokimab in Adults With Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) (NCT NCT03614923)
NCT ID: NCT03614923
Last Updated: 2022-01-24
Results Overview
Nasal polyps were evaluated by nasal endoscopy using centralized imaging data assessments scored by an independent reviewer. Each nostril was scored on a scale from 0 to 4, where a score of 0 means no polyps, and a score of 4 means the presence of polyps causing complete obstruction of the inferior nasal cavity. The bilateral NPS score is the sum of the right and left nostril scores, and hence the total NPS value is between 0 and 8 (worst). A negative change from Baseline indicates improvement.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
105 participants
Primary outcome timeframe
Baseline and Week 16
Results posted on
2022-01-24
Participant Flow
This study was conducted at 26 sites in the United States.
All participants entered a run-in period of between 20 and 31 days on mometasone furoate nasal spray (MFNS) of two actuations (50 μg/actuation) in each nostril twice daily (BID) prior to Day 1. Eligible participants were randomly assigned on Day 1 to one of three treatment arms in a 1:1:1 ratio. Randomization was stratified by asthma comorbidity.
Participant milestones
| Measure |
Etokimab 300 mg + 150 mg Q4W
Participants received a 300 mg loading dose of etokimab administered by subcutaneous injection at Week 0 then 150 mg etokimab by subcutaneous injection every 4 weeks (Q4W) up to Week 12 (Weeks 4, 8, and 12). Participants also used mometasone furoate nasal spray (MFNS) of 2 actuations (50 μg/actuation) in each nostril twice daily (BID).
|
Etokimab 300 mg + 150 mg Q8W
Participants received a 300 mg loading dose of etokimab administered by subcutaneous injection at Week 0 then etokimab 150 mg by subcutaneous injection every 8 weeks (Q8W) up to Week 12 and placebo at Weeks 4 and 12. Participants also used MFNS of 2 actuations (50 μg/actuation) in each nostril BID.
|
Placebo
Participants received placebo subcutaneous injection once every 4 weeks up to Week 12. Participants also used MFNS of 2 actuations (50 μg/actuation) in each nostril BID.
|
|---|---|---|---|
|
Overall Study
STARTED
|
35
|
35
|
35
|
|
Overall Study
COMPLETED
|
30
|
30
|
30
|
|
Overall Study
NOT COMPLETED
|
5
|
5
|
5
|
Reasons for withdrawal
| Measure |
Etokimab 300 mg + 150 mg Q4W
Participants received a 300 mg loading dose of etokimab administered by subcutaneous injection at Week 0 then 150 mg etokimab by subcutaneous injection every 4 weeks (Q4W) up to Week 12 (Weeks 4, 8, and 12). Participants also used mometasone furoate nasal spray (MFNS) of 2 actuations (50 μg/actuation) in each nostril twice daily (BID).
|
Etokimab 300 mg + 150 mg Q8W
Participants received a 300 mg loading dose of etokimab administered by subcutaneous injection at Week 0 then etokimab 150 mg by subcutaneous injection every 8 weeks (Q8W) up to Week 12 and placebo at Weeks 4 and 12. Participants also used MFNS of 2 actuations (50 μg/actuation) in each nostril BID.
|
Placebo
Participants received placebo subcutaneous injection once every 4 weeks up to Week 12. Participants also used MFNS of 2 actuations (50 μg/actuation) in each nostril BID.
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
1
|
1
|
|
Overall Study
Adverse Event
|
0
|
2
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
1
|
|
Overall Study
Lack of Efficacy
|
2
|
0
|
1
|
|
Overall Study
Non-compliance
|
0
|
1
|
0
|
|
Overall Study
Other
|
0
|
1
|
1
|
Baseline Characteristics
The full analysis set included all randomized participants who received at least one dose of etokimab or placebo, and had a Baseline and at least one post-Baseline NPS and/or SNOT-22 score up to Week 16.
Baseline characteristics by cohort
| Measure |
Etokimab 300 mg + 150 mg Q4W
n=35 Participants
Participants received a 300 mg loading dose of etokimab administered by subcutaneous injection at Week 0 then 150 mg etokimab by subcutaneous injection Q4W up to Week 12 (Weeks 4, 8, and 12). Participants also used MFNS of 2 actuations (50 μg/actuation) in each nostril BID.
|
Etokimab 300 mg + 150 mg Q8W
n=35 Participants
Participants received a 300 mg loading dose of etokimab administered by subcutaneous injection at Week 0 then etokimab 150 mg by subcutaneous injection Q8W up to Week 12 and placebo at Weeks 4 and 12. Participants also used MFNS of 2 actuations (50 μg/actuation) in each nostril BID.
|
Placebo
n=35 Participants
Participants received placebo subcutaneous injection once every 4 weeks up to Week 12. Participants also used MFNS of 2 actuations (50 μg/actuation) in each nostril BID.
|
Total
n=105 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
49.1 years
STANDARD_DEVIATION 14.82 • n=35 Participants
|
48.2 years
STANDARD_DEVIATION 10.28 • n=35 Participants
|
49.5 years
STANDARD_DEVIATION 12.68 • n=35 Participants
|
49.0 years
STANDARD_DEVIATION 12.62 • n=105 Participants
|
|
Age, Customized
<65 years
|
32 Participants
n=35 Participants
|
35 Participants
n=35 Participants
|
31 Participants
n=35 Participants
|
98 Participants
n=105 Participants
|
|
Age, Customized
>=65 years
|
3 Participants
n=35 Participants
|
0 Participants
n=35 Participants
|
4 Participants
n=35 Participants
|
7 Participants
n=105 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=35 Participants
|
12 Participants
n=35 Participants
|
9 Participants
n=35 Participants
|
29 Participants
n=105 Participants
|
|
Sex: Female, Male
Male
|
27 Participants
n=35 Participants
|
23 Participants
n=35 Participants
|
26 Participants
n=35 Participants
|
76 Participants
n=105 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=35 Participants
|
2 Participants
n=35 Participants
|
5 Participants
n=35 Participants
|
13 Participants
n=105 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
29 Participants
n=35 Participants
|
33 Participants
n=35 Participants
|
30 Participants
n=35 Participants
|
92 Participants
n=105 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=35 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=105 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=35 Participants
|
1 Participants
n=35 Participants
|
0 Participants
n=35 Participants
|
1 Participants
n=105 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=35 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=105 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=35 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=105 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=35 Participants
|
5 Participants
n=35 Participants
|
5 Participants
n=35 Participants
|
12 Participants
n=105 Participants
|
|
Race (NIH/OMB)
White
|
33 Participants
n=35 Participants
|
29 Participants
n=35 Participants
|
30 Participants
n=35 Participants
|
92 Participants
n=105 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=35 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=105 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=35 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=105 Participants
|
|
Nasal Polyp Score (NPS)
|
5.4 score on a scale
STANDARD_DEVIATION 1.58 • n=34 Participants • The full analysis set included all randomized participants who received at least one dose of etokimab or placebo, and had a Baseline and at least one post-Baseline NPS and/or SNOT-22 score up to Week 16.
|
5.2 score on a scale
STANDARD_DEVIATION 2.01 • n=35 Participants • The full analysis set included all randomized participants who received at least one dose of etokimab or placebo, and had a Baseline and at least one post-Baseline NPS and/or SNOT-22 score up to Week 16.
|
5.7 score on a scale
STANDARD_DEVIATION 1.86 • n=35 Participants • The full analysis set included all randomized participants who received at least one dose of etokimab or placebo, and had a Baseline and at least one post-Baseline NPS and/or SNOT-22 score up to Week 16.
|
5.4 score on a scale
STANDARD_DEVIATION 1.83 • n=104 Participants • The full analysis set included all randomized participants who received at least one dose of etokimab or placebo, and had a Baseline and at least one post-Baseline NPS and/or SNOT-22 score up to Week 16.
|
|
Sino-Nasal Outcome Test (SNOT-22) Score
|
51.4 score on a scale
STANDARD_DEVIATION 19.73 • n=34 Participants • The full analysis set included all randomized participants who received at least one dose of etokimab or placebo, and had a Baseline and at least one post-Baseline NPS and/or SNOT-22 score up to Week 16.
|
53.9 score on a scale
STANDARD_DEVIATION 23.67 • n=35 Participants • The full analysis set included all randomized participants who received at least one dose of etokimab or placebo, and had a Baseline and at least one post-Baseline NPS and/or SNOT-22 score up to Week 16.
|
56.9 score on a scale
STANDARD_DEVIATION 21.69 • n=35 Participants • The full analysis set included all randomized participants who received at least one dose of etokimab or placebo, and had a Baseline and at least one post-Baseline NPS and/or SNOT-22 score up to Week 16.
|
54.1 score on a scale
STANDARD_DEVIATION 21.78 • n=104 Participants • The full analysis set included all randomized participants who received at least one dose of etokimab or placebo, and had a Baseline and at least one post-Baseline NPS and/or SNOT-22 score up to Week 16.
|
PRIMARY outcome
Timeframe: Baseline and Week 16Population: Full analysis set with available data
Nasal polyps were evaluated by nasal endoscopy using centralized imaging data assessments scored by an independent reviewer. Each nostril was scored on a scale from 0 to 4, where a score of 0 means no polyps, and a score of 4 means the presence of polyps causing complete obstruction of the inferior nasal cavity. The bilateral NPS score is the sum of the right and left nostril scores, and hence the total NPS value is between 0 and 8 (worst). A negative change from Baseline indicates improvement.
Outcome measures
| Measure |
Etokimab 300 mg + 150 mg Q4W
n=29 Participants
Participants received a 300 mg loading dose of etokimab administered by subcutaneous injection at Week 0 then 150 mg etokimab by subcutaneous injection Q4W up to Week 12 (Weeks 4, 8, and 12). Participants also used MFNS of 2 actuations (50 μg/actuation) in each nostril BID.
|
Etokimab 300 mg + 150 mg Q8W
n=33 Participants
Participants received a 300 mg loading dose of etokimab administered by subcutaneous injection at Week 0 then etokimab 150 mg by subcutaneous injection Q8W up to Week 12 and placebo at Weeks 4 and 12. Participants also used MFNS of 2 actuations (50 μg/actuation) in each nostril BID.
|
Placebo
n=31 Participants
Participants received placebo subcutaneous injection once every 4 weeks up to Week 12. Participants also used MFNS of 2 actuations (50 μg/actuation) in each nostril BID.
|
|---|---|---|---|
|
Change From Baseline in Nasal Polyp Score (NPS) to Week 16
|
-0.87 score on a scale
Standard Error 0.225
|
-0.89 score on a scale
Standard Error 0.221
|
-0.49 score on a scale
Standard Error 0.225
|
PRIMARY outcome
Timeframe: Baseline and Week 16Population: Full analysis set participants with available data
SNOT-22 is a 22-item outcome measure on a 5-category scale that assesses symptoms and social/emotional consequences of rhinosinusitis. Each item is scored from 0 (No problem at all) to 5 (Problem as bad as it can be), and the total score ranges from 0 to 110. Higher SNOT-22 scores are indicative of greater impact of rhinosinusitis on quality of life. A negative change from Baseline indicates improvement.
Outcome measures
| Measure |
Etokimab 300 mg + 150 mg Q4W
n=30 Participants
Participants received a 300 mg loading dose of etokimab administered by subcutaneous injection at Week 0 then 150 mg etokimab by subcutaneous injection Q4W up to Week 12 (Weeks 4, 8, and 12). Participants also used MFNS of 2 actuations (50 μg/actuation) in each nostril BID.
|
Etokimab 300 mg + 150 mg Q8W
n=33 Participants
Participants received a 300 mg loading dose of etokimab administered by subcutaneous injection at Week 0 then etokimab 150 mg by subcutaneous injection Q8W up to Week 12 and placebo at Weeks 4 and 12. Participants also used MFNS of 2 actuations (50 μg/actuation) in each nostril BID.
|
Placebo
n=31 Participants
Participants received placebo subcutaneous injection once every 4 weeks up to Week 12. Participants also used MFNS of 2 actuations (50 μg/actuation) in each nostril BID.
|
|---|---|---|---|
|
Change From Baseline in Sino-Nasal Outcome Test-22 (SNOT-22) Score at Week 16
|
-22.97 score on a scale
Standard Error 3.084
|
-18.34 score on a scale
Standard Error 3.077
|
-16.32 score on a scale
Standard Error 3.112
|
SECONDARY outcome
Timeframe: Baseline, Week 16, and Week 24Population: Safety analysis set with available data at each time point
Outcome measures
| Measure |
Etokimab 300 mg + 150 mg Q4W
n=35 Participants
Participants received a 300 mg loading dose of etokimab administered by subcutaneous injection at Week 0 then 150 mg etokimab by subcutaneous injection Q4W up to Week 12 (Weeks 4, 8, and 12). Participants also used MFNS of 2 actuations (50 μg/actuation) in each nostril BID.
|
Etokimab 300 mg + 150 mg Q8W
n=35 Participants
Participants received a 300 mg loading dose of etokimab administered by subcutaneous injection at Week 0 then etokimab 150 mg by subcutaneous injection Q8W up to Week 12 and placebo at Weeks 4 and 12. Participants also used MFNS of 2 actuations (50 μg/actuation) in each nostril BID.
|
Placebo
n=35 Participants
Participants received placebo subcutaneous injection once every 4 weeks up to Week 12. Participants also used MFNS of 2 actuations (50 μg/actuation) in each nostril BID.
|
|---|---|---|---|
|
Change From Baseline in Eosinophil Count
Baseline
|
0.437 10^9 cells/L
Standard Deviation 0.2546
|
0.350 10^9 cells/L
Standard Deviation 0.2038
|
0.434 10^9 cells/L
Standard Deviation 0.2490
|
|
Change From Baseline in Eosinophil Count
Change from Baseline at Week 16
|
-0.162 10^9 cells/L
Standard Deviation 0.1717
|
-0.117 10^9 cells/L
Standard Deviation 0.1718
|
-0.020 10^9 cells/L
Standard Deviation 0.1843
|
|
Change From Baseline in Eosinophil Count
Change from Baseline at Week 24
|
-0.038 10^9 cells/L
Standard Deviation 0.2451
|
-0.029 10^9 cells/L
Standard Deviation 0.1674
|
0.019 10^9 cells/L
Standard Deviation 0.2151
|
Adverse Events
Etokimab 300 mg + 150 mg Q4W
Serious events: 2 serious events
Other events: 8 other events
Deaths: 0 deaths
Etokimab 300 mg + 150 mg Q8W
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Etokimab 300 mg + 150 mg Q4W
n=35 participants at risk
Participants received a 300 mg loading dose of etokimab administered by subcutaneous injection at Week 0 then 150 mg etokimab by subcutaneous injection Q4W up to Week 12 (Weeks 4, 8, and 12). Participants also used MFNS of 2 actuations (50 μg/actuation) in each nostril BID.
|
Etokimab 300 mg + 150 mg Q8W
n=35 participants at risk
Participants received a 300 mg loading dose of etokimab administered by subcutaneous injection at Week 0 then etokimab 150 mg by subcutaneous injection Q8W up to Week 12 and placebo at Weeks 4 and 12. Participants also used MFNS of 2 actuations (50 μg/actuation) in each nostril BID.
|
Placebo
n=35 participants at risk
Participants received placebo subcutaneous injection once every 4 weeks up to Week 12. Participants also used MFNS of 2 actuations (50 μg/actuation) in each nostril BID.
|
|---|---|---|---|
|
Infections and infestations
Urinary tract infection
|
2.9%
1/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
0.00%
0/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
0.00%
0/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
|
Renal and urinary disorders
Hydronephrosis
|
2.9%
1/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
0.00%
0/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
0.00%
0/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
|
Renal and urinary disorders
Ureterolithiasis
|
2.9%
1/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
0.00%
0/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
0.00%
0/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
2.9%
1/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
0.00%
0/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
0.00%
0/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
Other adverse events
| Measure |
Etokimab 300 mg + 150 mg Q4W
n=35 participants at risk
Participants received a 300 mg loading dose of etokimab administered by subcutaneous injection at Week 0 then 150 mg etokimab by subcutaneous injection Q4W up to Week 12 (Weeks 4, 8, and 12). Participants also used MFNS of 2 actuations (50 μg/actuation) in each nostril BID.
|
Etokimab 300 mg + 150 mg Q8W
n=35 participants at risk
Participants received a 300 mg loading dose of etokimab administered by subcutaneous injection at Week 0 then etokimab 150 mg by subcutaneous injection Q8W up to Week 12 and placebo at Weeks 4 and 12. Participants also used MFNS of 2 actuations (50 μg/actuation) in each nostril BID.
|
Placebo
n=35 participants at risk
Participants received placebo subcutaneous injection once every 4 weeks up to Week 12. Participants also used MFNS of 2 actuations (50 μg/actuation) in each nostril BID.
|
|---|---|---|---|
|
Infections and infestations
Sinusitis
|
5.7%
2/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
14.3%
5/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
11.4%
4/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
|
Nervous system disorders
Headache
|
2.9%
1/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
8.6%
3/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
2.9%
1/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
|
Infections and infestations
Upper respiratory tract infection
|
5.7%
2/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
2.9%
1/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
2.9%
1/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
|
General disorders
Injection site erythema
|
5.7%
2/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
2.9%
1/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
0.00%
0/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
|
Vascular disorders
Hypertension
|
5.7%
2/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
0.00%
0/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
0.00%
0/35 • From first dose of study medication on Day 1 until Week 16, or up to 28 days after the last dose of study medication for participants who discontinued treatment earlier than Week 16.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Results from a center cannot be submitted for publication before results of multicenter study are published unless it is 18 months since study completion. Then, Investigator can publish if manuscript is submitted to Sponsor 90 days prior to submission. Sponsor may require the Investigator to remove specifically identified Confidential Information (other than Trial Data) and/or to delay the proposed publication for an additional 60 days to enable Sponsor to seek patent protection for Inventions.
- Publication restrictions are in place
Restriction type: OTHER