Chronic Rhinosinusitis
Conditions
Keywords
ANB020, Etokimab, CRSwNP
Brief summary
A study to evaluate the safety and efficacy of multiple doses of etokimab in adults with chronic rhinosinusitis with nasal polyps.
Detailed description
This study is a randomized, placebo controlled, double-blind, multi-dose study to assess the efficacy of two different dose regimens of etokimab compared to placebo in adults with moderate-to-severe chronic sinusitis with nasal polyposis (CRSwNP). During the screening period, all subjects will undergo evaluation for eligibility. A centralized reader will be used to confirm the diagnosis of CRSwNP as assessed by nasal endoscopy, computed tomography (CT) scan of sinuses, and symptom scoring to reduce the risk of interpretation variation. Participants will also be provided mometasone furoate nasal spray (MFNS) for use during the trial and are required to undergo a minimum run-in period of 20 days prior to Day 1 with approximately 80% compliance. Participants will be randomly assigned on Day 1 to one of the three treatment arms in a 1:1:1 ratio.
Interventions
BIOLOGICALEtokimab
Administered by subcutaneous injection
BIOLOGICALPlacebo
Administered by subcutaneous injection
DRUGMometasone Furoate Nasal Spray
Mometasone Furoate Nasal Spray (MFNS) was used from 4 weeks prior to Day 1 (Run-in period) through the end of the study. Participants used 2 actuations (50 μg/actuation) in each nostril BID, total daily dose of 400 μg. Participants intolerant to BID intranasal corticosteroids (INCS) could use the lower dose regimen of 1 actuation in each nostril BID, total daily dose of 200 μg.
Sponsors
AnaptysBio, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Clinically confirmed diagnosis of CRSwNP * Nasal polyp score (NPS) ≥ 4 out of a maximum score for both nostrils (with at least a score of 1 for each nostril). * 22 Item Sino-Nasal Outcome Test (SNOT-22) score \> 15. * Presence of at least two of the following symptoms prior to screening: nasal blockade/obstruction/congestion or nasal discharge (anterior/posterior nasal drip); facial pain/pressure; reduction or loss of smell * Body mass index (BMI) of 18 to 42 kg/m\^2 (inclusive) and total body weight \> 50 kg (110 lb). BMI=weight (kg)/(height \[m\^2\]).
Exclusion criteria
* Use of investigational drugs or prohibited therapy for this study within 8 weeks before screening or 5 half-lives, whichever is longer. * Have experienced severe life threatening anaphylactic reactions. * Participation in any interventional study for the treatment of CRSwNP in the 3 months before screening. * If female, is pregnant or lactating, or intend to become pregnant during the study period. * History (or suspected history) of alcohol or substance abuse. * Current smokers or former smokers with a smoking history of ≥ 10 pack years. If a patient has less than 10 pack years smoking history, he or she should have quit smoking at least 2 months before screening to enroll in the study. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Nasal Polyp Score (NPS) to Week 16 | Baseline and Week 16 | 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. |
| Change From Baseline in Sino-Nasal Outcome Test-22 (SNOT-22) Score at Week 16 | Baseline and Week 16 | 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. |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in Eosinophil Count | Baseline, Week 16, and Week 24 |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 26 sites in the United States.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 Q4W up to Week 12 (Weeks 4, 8, and 12). Participants also used MFNS of 2 actuations (50 μg/actuation) in each nostril BID. | 35 |
| 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 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. | 35 |
| 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. | 35 |
| Total | 105 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 1 |
| Overall Study | Lack of Efficacy | 2 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 |
| Overall Study | Non-compliance | 0 | 1 | 0 |
| Overall Study | Other | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | Etokimab 300 mg + 150 mg Q4W | Etokimab 300 mg + 150 mg Q8W |
|---|---|---|---|---|
| Age, Continuous | 49.5 years STANDARD_DEVIATION 12.68 | 49.0 years STANDARD_DEVIATION 12.62 | 49.1 years STANDARD_DEVIATION 14.82 | 48.2 years STANDARD_DEVIATION 10.28 |
| Age, Customized <65 years | 31 Participants | 98 Participants | 32 Participants | 35 Participants |
| Age, Customized >=65 years | 4 Participants | 7 Participants | 3 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 13 Participants | 6 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 92 Participants | 29 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Nasal Polyp Score (NPS) | 5.7 score on a scale STANDARD_DEVIATION 1.86 | 5.4 score on a scale STANDARD_DEVIATION 1.83 | 5.4 score on a scale STANDARD_DEVIATION 1.58 | 5.2 score on a scale STANDARD_DEVIATION 2.01 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 12 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 30 Participants | 92 Participants | 33 Participants | 29 Participants |
| Sex: Female, Male Female | 9 Participants | 29 Participants | 8 Participants | 12 Participants |
| Sex: Female, Male Male | 26 Participants | 76 Participants | 27 Participants | 23 Participants |
| Sino-Nasal Outcome Test (SNOT-22) Score | 56.9 score on a scale STANDARD_DEVIATION 21.69 | 54.1 score on a scale STANDARD_DEVIATION 21.78 | 51.4 score on a scale STANDARD_DEVIATION 19.73 | 53.9 score on a scale STANDARD_DEVIATION 23.67 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 35 | 0 / 35 |
| other Total, other adverse events | 8 / 35 | 8 / 35 | 6 / 35 |
| serious Total, serious adverse events | 2 / 35 | 0 / 35 | 0 / 35 |
Outcome results
Primary
Change From Baseline in Nasal Polyp Score (NPS) to Week 16
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.
Time frame: Baseline and Week 16
Population: Full analysis set with available data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Etokimab 300 mg + 150 mg Q4W | Change From Baseline in Nasal Polyp Score (NPS) to Week 16 | -0.87 score on a scale | Standard Error 0.225 |
| Etokimab 300 mg + 150 mg Q8W | Change From Baseline in Nasal Polyp Score (NPS) to Week 16 | -0.89 score on a scale | Standard Error 0.221 |
| Placebo | Change From Baseline in Nasal Polyp Score (NPS) to Week 16 | -0.49 score on a scale | Standard Error 0.225 |
Comparison: A general linear mixed effects model with repeated measures (MMRM) was used including the change from Baseline in NPS as dependent variable; treatment group, stratification factor, time (Weeks 4, 8, 12, and 16), treatment by stratification factor, and treatment by time interaction as fixed effect factors; Baseline NPS as covariate; and subject as random effect.p-value: 0.236495% CI: [-1.01, 0.25]General linear MMRM
Comparison: A general linear mixed effects model with repeated measures (MMRM) was used including the change from Baseline in NPS as dependent variable; treatment group, stratification factor, time (Weeks 4, 8, 12, and 16), treatment by stratification factor, and treatment by time interaction as fixed effect factors; Baseline NPS as covariate; and subject as random effect.p-value: 0.202495% CI: [-1.03, 0.22]General linear MMRM
Primary
Change From Baseline in Sino-Nasal Outcome Test-22 (SNOT-22) Score at Week 16
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.
Time frame: Baseline and Week 16
Population: Full analysis set participants with available data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Etokimab 300 mg + 150 mg Q4W | 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 |
| Etokimab 300 mg + 150 mg Q8W | Change From Baseline in Sino-Nasal Outcome Test-22 (SNOT-22) Score at Week 16 | -18.34 score on a scale | Standard Error 3.077 |
| Placebo | Change From Baseline in Sino-Nasal Outcome Test-22 (SNOT-22) Score at Week 16 | -16.32 score on a scale | Standard Error 3.112 |
Comparison: A general linear mixed effects model with repeated measures (MMRM) was used including the change from Baseline in SNOT-22 as dependent variable; treatment group, stratification factor, time (Weeks 4, 8, 12, and 16), treatment by stratification factor, and treatment by time interaction as fixed effect factors; Baseline SNOT-22 as covariate; and subject as random effect.p-value: 0.13395% CI: [-15.34, 2.06]General linear MMRM
Comparison: A general linear mixed effects model with repeated measures (MMRM) was used including the change from Baseline in SNOT-22 as dependent variable; treatment group, stratification factor, time (Weeks 4, 8, 12, and 16), treatment by stratification factor, and treatment by time interaction as fixed effect factors; Baseline SNOT-22 as covariate; and subject as random effect.p-value: 0.646495% CI: [-10.7, 6.67]General linear MMRM
Secondary
Change From Baseline in Eosinophil Count
Time frame: Baseline, Week 16, and Week 24
Population: Safety analysis set with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Etokimab 300 mg + 150 mg Q4W | Change From Baseline in Eosinophil Count | Baseline | 0.437 10^9 cells/L | Standard Deviation 0.2546 |
| Etokimab 300 mg + 150 mg Q4W | Change From Baseline in Eosinophil Count | Change from Baseline at Week 16 | -0.162 10^9 cells/L | Standard Deviation 0.1717 |
| Etokimab 300 mg + 150 mg Q4W | Change From Baseline in Eosinophil Count | Change from Baseline at Week 24 | -0.038 10^9 cells/L | Standard Deviation 0.2451 |
| Etokimab 300 mg + 150 mg Q8W | Change From Baseline in Eosinophil Count | Change from Baseline at Week 24 | -0.029 10^9 cells/L | Standard Deviation 0.1674 |
| Etokimab 300 mg + 150 mg Q8W | Change From Baseline in Eosinophil Count | Change from Baseline at Week 16 | -0.117 10^9 cells/L | Standard Deviation 0.1718 |
| Etokimab 300 mg + 150 mg Q8W | Change From Baseline in Eosinophil Count | Baseline | 0.350 10^9 cells/L | Standard Deviation 0.2038 |
| Placebo | Change From Baseline in Eosinophil Count | Baseline | 0.434 10^9 cells/L | Standard Deviation 0.249 |
| Placebo | Change From Baseline in Eosinophil Count | Change from Baseline at Week 16 | -0.020 10^9 cells/L | Standard Deviation 0.1843 |
| Placebo | Change From Baseline in Eosinophil Count | Change from Baseline at Week 24 | 0.019 10^9 cells/L | Standard Deviation 0.2151 |