Allergic Bronchopulmonary Aspergillosis
Conditions
Brief summary
The primary objective of the study is to evaluate the efficacy of dupilumab on lung function in participants with Allergic Bronchopulmonary Aspergillosis (ABPA). The secondary objectives of the study are: * To evaluate the effects of dupilumab on exacerbations in participants with ABPA * To evaluate the effects of dupilumab on ABPA-related exacerbations * To evaluate the effects of dupilumab on hospitalization/emergency department (ED)/urgent care visits in participants with ABPA * To evaluate the effects of dupilumab on asthma control in participants with ABPA * To evaluate the effects of dupilumab on health-related quality of life (HRQoL) in participants with ABPA * To evaluate the effects of dupilumab on serum total immunoglobulin E (IgE) and Aspergillus-specific IgE concentrations * To evaluate the effects of dupilumab on Fractional exhaled Nitric Oxide (FeNO) levels * To evaluate safety and tolerability of dupilumab in participants with ABPA * To evaluate dupilumab concentrations in serum and the incidence of anti-dupilumab antibodies in participants with ABPA
Interventions
DRUGdupilumab
Single-use prefilled glass syringe administered by subcutaneous (SC) injection.
DRUGPlacebo
Matching placebo
Sponsors
Sanofi
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Diagnosis of both ABPA and asthma * On a maintenance therapy for their asthma with controller medication which must include inhaled corticosteroids (ICS) and may include 1 or more additional controller medications including a long-acting beta agonist (LABA), leukotriene receptor antagonist (LTRA), and/or long-acting muscarinic receptor antagonist (LAMA), etc for at least 12 weeks, with a stable dose and regimen with no change in the dose or frequency of administration for at least 4 weeks prior to the screening visit and between the screening and baseline/randomization visits * For participants on OCS (oral corticosteroid): must be on a chronic stable dose (no change in the dose) of OCS of up to 10 mg/day (for participants taking daily corticosteroids) or up to 30 mg every alternate day (for participants taking alternate day corticosteroids) (prednisone/prednisolone or the equivalent) for at least 4 weeks prior to the screening visit and between the screening and the baseline/randomization visit * Must have experienced ≥1 severe respiratory exacerbation requiring treatment with systemic corticosteroids or hospitalization or treatment in ED/urgent care within 12 months prior to the screening visit or must be receiving chronic stable low-dose OCS per above criteria Key
Exclusion criteria
* Weight less than 30.0 kilograms * Current smoker or e-cigarette user, cessation of smoking or e-cigarette use within 6 months prior to randomization, or \>=10 pack-years smoking history * Post-bronchodilator FEV1 \<30% predicted normal at screening * Respiratory exacerbation requiring systemic corticosteroids within 4 weeks prior to screening and between screening and baseline visit (for patients on daily or alternate day OCS, exacerbation requiring at least double the maintenance dose of corticosteroids) * Upper or lower respiratory tract infection within the 4 weeks prior to screening (visit 1) or between the screening and randomization visits * Significant chronic pulmonary disease other than asthma complicated with ABPA (eg, physician-diagnosed bronchiectasis due to a condition other than ABPA; cystic fibrosis; sarcoidosis; interstitial lung disease not due to ABPA; chronic obstructive pulmonary disease \[COPD\] not due to ABPA; hypereosinophilic syndrome; etc), a diagnosed pulmonary or systemic disease associated with elevated peripheral eosinophil counts * Diagnosis or suspected diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) (also called Churg-Strauss Syndrome) NOTE: Other protocol defined inclusion /
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) Compared to Placebo | At Week 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Rate of Severe Respiratory Exacerbations | Over the 24 to 52 Week Treatment Period | Defined as new onset of symptoms or clinical worsening of respiratory symptoms requiring systemic corticosteroid treatment for ≥3 consecutive days; for participants who are on maintenance systemic corticosteroids, at least double the dose of maintenance systemic corticosteroids for ≥3 consecutive days (with or without antibiotic therapy if indicated) Adjusted Rate: Negative Binomial Regression Model Unadjusted Rate: (Number of events)/(number of participant years) |
| Annualized Rate of Severe Respiratory Exacerbations Requiring Either Hospitalization or Observation for >24 Hours in an ED/Urgent Care Facility | Over the 24 to 52 Week Treatment Period | Annualized rate of severe respiratory exacerbations requiring either hospitalization or observation for \>24 hours in an emergency department/urgent care facility (events per person-year) Adjusted Rate: Negative Binomial Regression Model Unadjusted Rate: (Number of events)/(number of participant years) |
| Change From Baseline in Asthma Control Questionnaire (ACQ)-5 Score | Over the 24 to 52 Week Treatment Period | ACQ is completed by patient to measure both the adequacy of asthma control and change in asthma control, which occurs either spontaneously or as a result of treatment. The ACQ-5 score is the mean of the first 5 questions, between 0 (totally controlled) and 6 (severely uncontrolled). A higher score indicates lower asthma control. Participants with a score below 1.0 reflect adequately controlled asthma and participants with scores above 1.0 reflect inadequately controlled asthma. The optimal cut-point score of 1.50 should be used to be confident that a patient has inadequately controlled asthma. |
| Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score | Over the 24 to 52 Week Treatment Period | SGRQ will be completed by the patient to measure and quantify health status in adult participants with chronic airflow limitation. Total score ranges from 0 to 100. Scores by dimension are calculated for three domains: Symptoms, Activity, and Impacts (Psychosocial). Lower score indicates better Quality of Life (QoL). |
| Percentage of Participants Achieving a Reduction in the SGRQ Total Score of 4 Points or Greater From Baseline | Up to 52 Weeks | SGRQ will be completed by the patient to measure and quantify health status in adult participants with chronic airflow limitation. Total score ranges from 0 to 100. Scores by dimension are calculated for three domains: Symptoms, Activity, and Impacts (Psychosocial). Lower score indicates better Quality of Life (QoL). |
| Percent Change From Baseline in Total IgE in Serum | Over the 24 to 52 Week Treatment Period | — |
| Annualized Rate of ABPA-related Exacerbations | Over the 24 to 52 Week Treatment Period | Defined as severe respiratory exacerbations that are associated with a doubling of serum total Immunoglobulin E (IgE) from the prior pre-exacerbation value. Adjusted Rate: Negative Binomial Regression Model Unadjusted Rate: (Number of events)/(number of participant years) |
| Absolute Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) | Over the 24 to 52 Week Treatment Period | — |
| Percent Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) | Over the 24 to 52 Week Treatment Period | — |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) From Baseline | Through the end of the 52 Week Treatment Period | — |
| Number of Participants With Treatment-emergent Anti-drug Antibody (ADA) Responses and Titer Over Time | Up to 64 Weeks | — |
| Concentrations of Functional Dupilumab in Serum by Treatment Regimen | Up to 64 Weeks | — |
| Percent Change From Baseline in A Fumigatus-specific IgE in Serum | Over the 24 to 52 Week Treatment Period | — |
Countries
Bulgaria, France, Germany, Hungary, Japan, Netherlands, Poland, Romania, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching dupilumab without active substance | 27 |
| Dupilumab 300 mg Q2W Subcutaneous (SC) dose every two weeks (Q2W) | 35 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Decision by the Investigator/Sponsor | 1 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Protocol Deviation | 0 | 1 |
| Overall Study | Travel Limitations | 1 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Placebo | Dupilumab 300 mg Q2W | Total |
|---|---|---|---|
| Age, Customized | 57.1 years STANDARD_DEVIATION 14.38 | 61.2 years STANDARD_DEVIATION 8.62 | 59.4 years STANDARD_DEVIATION 11.56 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 29 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 4 Participants | 5 Participants |
| Race/Ethnicity, Customized Not Reported | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 25 Participants | 28 Participants | 53 Participants |
| Sex: Female, Male Female | 17 Participants | 22 Participants | 39 Participants |
| Sex: Female, Male Male | 10 Participants | 13 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 27 | 1 / 35 |
| other Total, other adverse events | 19 / 27 | 29 / 35 |
| serious Total, serious adverse events | 5 / 27 | 3 / 35 |
Outcome results
Primary
Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) Compared to Placebo
Time frame: At Week 24
Population: Randomized participants with available data for analysis in the statistical model
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) Compared to Placebo | 0.002 Liters | Standard Error 0.0558 |
| Dupilumab 300 mg Q2W | Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) Compared to Placebo | 0.203 Liters | Standard Error 0.0482 |
p-value: 0.002295% CI: [0.0768, 0.3256]Mixed Models Analysis
Secondary
Absolute Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO)
Time frame: Over the 24 to 52 Week Treatment Period
Population: Number of randomized patients with a baseline measurement and at least one post-baseline measurement at the post-baseline time point of interest
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) | Week 24 | -4.80 ppb | Standard Deviation 23.521 |
| Placebo | Absolute Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) | Week 36 | 3.11 ppb | Standard Deviation 20.571 |
| Placebo | Absolute Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) | Week 44 | 1.38 ppb | Standard Deviation 21.896 |
| Placebo | Absolute Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) | Week 52 | -4.79 ppb | Standard Deviation 27.634 |
| Dupilumab 300 mg Q2W | Absolute Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) | Week 52 | -19.04 ppb | Standard Deviation 35.471 |
| Dupilumab 300 mg Q2W | Absolute Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) | Week 24 | -22.04 ppb | Standard Deviation 38.41 |
| Dupilumab 300 mg Q2W | Absolute Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) | Week 44 | -19.18 ppb | Standard Deviation 37.122 |
| Dupilumab 300 mg Q2W | Absolute Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) | Week 36 | -21.48 ppb | Standard Deviation 40.538 |
Secondary
Annualized Rate of ABPA-related Exacerbations
Defined as severe respiratory exacerbations that are associated with a doubling of serum total Immunoglobulin E (IgE) from the prior pre-exacerbation value. Adjusted Rate: Negative Binomial Regression Model Unadjusted Rate: (Number of events)/(number of participant years)
Time frame: Over the 24 to 52 Week Treatment Period
Population: The full analysis set (FAS) includes all randomized participants. It is based on the treatment allocated as randomized
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Annualized Rate of ABPA-related Exacerbations | Adjusted Rate | NA Events per person-year |
| Placebo | Annualized Rate of ABPA-related Exacerbations | Unadjusted Rate | 0 Events per person-year |
| Dupilumab 300 mg Q2W | Annualized Rate of ABPA-related Exacerbations | Adjusted Rate | NA Events per person-year |
| Dupilumab 300 mg Q2W | Annualized Rate of ABPA-related Exacerbations | Unadjusted Rate | 0 Events per person-year |
Secondary
Annualized Rate of Severe Respiratory Exacerbations
Defined as new onset of symptoms or clinical worsening of respiratory symptoms requiring systemic corticosteroid treatment for ≥3 consecutive days; for participants who are on maintenance systemic corticosteroids, at least double the dose of maintenance systemic corticosteroids for ≥3 consecutive days (with or without antibiotic therapy if indicated) Adjusted Rate: Negative Binomial Regression Model Unadjusted Rate: (Number of events)/(number of participant years)
Time frame: Over the 24 to 52 Week Treatment Period
Population: The full analysis set (FAS) includes all randomized participants. It is based on the treatment allocated as randomized
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Annualized Rate of Severe Respiratory Exacerbations | Adjusted Rate | 1.551 Events per person year |
| Placebo | Annualized Rate of Severe Respiratory Exacerbations | Unadjusted Rate | 0.943 Events per person year |
| Dupilumab 300 mg Q2W | Annualized Rate of Severe Respiratory Exacerbations | Adjusted Rate | 0.695 Events per person year |
| Dupilumab 300 mg Q2W | Annualized Rate of Severe Respiratory Exacerbations | Unadjusted Rate | 0.545 Events per person year |
Secondary
Annualized Rate of Severe Respiratory Exacerbations Requiring Either Hospitalization or Observation for >24 Hours in an ED/Urgent Care Facility
Annualized rate of severe respiratory exacerbations requiring either hospitalization or observation for \>24 hours in an emergency department/urgent care facility (events per person-year) Adjusted Rate: Negative Binomial Regression Model Unadjusted Rate: (Number of events)/(number of participant years)
Time frame: Over the 24 to 52 Week Treatment Period
Population: The full analysis set (FAS) includes all randomized participants. It is based on the treatment allocated as randomized
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Annualized Rate of Severe Respiratory Exacerbations Requiring Either Hospitalization or Observation for >24 Hours in an ED/Urgent Care Facility | Adjusted Rate | NA Events per person year |
| Placebo | Annualized Rate of Severe Respiratory Exacerbations Requiring Either Hospitalization or Observation for >24 Hours in an ED/Urgent Care Facility | Unadjusted Rate | 0.041 Events per person year |
| Dupilumab 300 mg Q2W | Annualized Rate of Severe Respiratory Exacerbations Requiring Either Hospitalization or Observation for >24 Hours in an ED/Urgent Care Facility | Adjusted Rate | NA Events per person year |
| Dupilumab 300 mg Q2W | Annualized Rate of Severe Respiratory Exacerbations Requiring Either Hospitalization or Observation for >24 Hours in an ED/Urgent Care Facility | Unadjusted Rate | 0.128 Events per person year |
Secondary
Change From Baseline in Asthma Control Questionnaire (ACQ)-5 Score
ACQ is completed by patient to measure both the adequacy of asthma control and change in asthma control, which occurs either spontaneously or as a result of treatment. The ACQ-5 score is the mean of the first 5 questions, between 0 (totally controlled) and 6 (severely uncontrolled). A higher score indicates lower asthma control. Participants with a score below 1.0 reflect adequately controlled asthma and participants with scores above 1.0 reflect inadequately controlled asthma. The optimal cut-point score of 1.50 should be used to be confident that a patient has inadequately controlled asthma.
Time frame: Over the 24 to 52 Week Treatment Period
Population: Number of randomized patients with a baseline measurement and at least one post-baseline measurement at the post-baseline time point of interest
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Asthma Control Questionnaire (ACQ)-5 Score | Week 24 | -1.10 ACQ-5 Score | Standard Deviation 1.102 |
| Placebo | Change From Baseline in Asthma Control Questionnaire (ACQ)-5 Score | Week 36 | -0.81 ACQ-5 Score | Standard Deviation 0.878 |
| Placebo | Change From Baseline in Asthma Control Questionnaire (ACQ)-5 Score | Week 44 | -0.87 ACQ-5 Score | Standard Deviation 1.233 |
| Placebo | Change From Baseline in Asthma Control Questionnaire (ACQ)-5 Score | Week 52 | -0.84 ACQ-5 Score | Standard Deviation 1.183 |
| Dupilumab 300 mg Q2W | Change From Baseline in Asthma Control Questionnaire (ACQ)-5 Score | Week 52 | -1.29 ACQ-5 Score | Standard Deviation 1.241 |
| Dupilumab 300 mg Q2W | Change From Baseline in Asthma Control Questionnaire (ACQ)-5 Score | Week 24 | -1.24 ACQ-5 Score | Standard Deviation 1.081 |
| Dupilumab 300 mg Q2W | Change From Baseline in Asthma Control Questionnaire (ACQ)-5 Score | Week 44 | -1.01 ACQ-5 Score | Standard Deviation 1.359 |
| Dupilumab 300 mg Q2W | Change From Baseline in Asthma Control Questionnaire (ACQ)-5 Score | Week 36 | -1.15 ACQ-5 Score | Standard Deviation 1.208 |
Secondary
Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score
SGRQ will be completed by the patient to measure and quantify health status in adult participants with chronic airflow limitation. Total score ranges from 0 to 100. Scores by dimension are calculated for three domains: Symptoms, Activity, and Impacts (Psychosocial). Lower score indicates better Quality of Life (QoL).
Time frame: Over the 24 to 52 Week Treatment Period
Population: Number of randomized patients with a baseline measurement and at least one post-baseline measurement at the post-baseline time point of interest
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score | Week 12 | -9.463 SGRQ Total Score | Standard Deviation 16.3993 |
| Placebo | Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score | Week 24 | -7.626 SGRQ Total Score | Standard Deviation 14.5412 |
| Placebo | Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score | Week 36 | -8.796 SGRQ Total Score | Standard Deviation 16.4257 |
| Placebo | Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score | Week 52 | -8.938 SGRQ Total Score | Standard Deviation 15.3127 |
| Dupilumab 300 mg Q2W | Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score | Week 52 | -25.309 SGRQ Total Score | Standard Deviation 20.1035 |
| Dupilumab 300 mg Q2W | Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score | Week 12 | -17.956 SGRQ Total Score | Standard Deviation 14.6184 |
| Dupilumab 300 mg Q2W | Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score | Week 36 | -20.178 SGRQ Total Score | Standard Deviation 15.5266 |
| Dupilumab 300 mg Q2W | Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score | Week 24 | -23.079 SGRQ Total Score | Standard Deviation 15.9104 |
Secondary
Concentrations of Functional Dupilumab in Serum by Treatment Regimen
Time frame: Up to 64 Weeks
Population: Includes all randomized participants who received dupilumab and who had at least one non-missing dupilumab result following the first dose. The PKAS is based on the treatment received rather than as randomized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Concentrations of Functional Dupilumab in Serum by Treatment Regimen | Week 0 | 0 mg/L | Standard Deviation 0 |
| Placebo | Concentrations of Functional Dupilumab in Serum by Treatment Regimen | Week 12 | 63.8 mg/L | Standard Deviation 35.4 |
| Placebo | Concentrations of Functional Dupilumab in Serum by Treatment Regimen | Week 24 | 86.5 mg/L | Standard Deviation 53.6 |
| Placebo | Concentrations of Functional Dupilumab in Serum by Treatment Regimen | Week 52 | 82.2 mg/L | Standard Deviation 55.4 |
| Placebo | Concentrations of Functional Dupilumab in Serum by Treatment Regimen | Week 64 | 1.67 mg/L | Standard Deviation 4.38 |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) From Baseline
Time frame: Through the end of the 52 Week Treatment Period
Population: The safety analysis set (SAF) includes all randomized participants who received any study drug; it is based on the treatment received
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) From Baseline | 22 Participants with TEAEs |
| Dupilumab 300 mg Q2W | Number of Participants With Treatment-emergent Adverse Events (TEAEs) From Baseline | 30 Participants with TEAEs |
Secondary
Number of Participants With Treatment-emergent Anti-drug Antibody (ADA) Responses and Titer Over Time
Time frame: Up to 64 Weeks
Population: The Pharmacokinetic Analysis Set (PKAS) includes all randomized participants who received any study drug and who had at least one non-missing drug concentration result following the first dose of study drug. The PKAS is based on the treatment received rather than as randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Anti-drug Antibody (ADA) Responses and Titer Over Time | TE & TB Maximum Titer Category Low (<1,000) | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Anti-drug Antibody (ADA) Responses and Titer Over Time | TE & TB Maximum Titer Category Moderate (1,000 to 10,000) | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Anti-drug Antibody (ADA) Responses and Titer Over Time | TE & TB Maximum Titer Category High (>10,000) | 0 Participants |
| Dupilumab 300 mg Q2W | Number of Participants With Treatment-emergent Anti-drug Antibody (ADA) Responses and Titer Over Time | TE & TB Maximum Titer Category Low (<1,000) | 1 Participants |
| Dupilumab 300 mg Q2W | Number of Participants With Treatment-emergent Anti-drug Antibody (ADA) Responses and Titer Over Time | TE & TB Maximum Titer Category Moderate (1,000 to 10,000) | 0 Participants |
| Dupilumab 300 mg Q2W | Number of Participants With Treatment-emergent Anti-drug Antibody (ADA) Responses and Titer Over Time | TE & TB Maximum Titer Category High (>10,000) | 0 Participants |
Secondary
Percentage of Participants Achieving a Reduction in the SGRQ Total Score of 4 Points or Greater From Baseline
SGRQ will be completed by the patient to measure and quantify health status in adult participants with chronic airflow limitation. Total score ranges from 0 to 100. Scores by dimension are calculated for three domains: Symptoms, Activity, and Impacts (Psychosocial). Lower score indicates better Quality of Life (QoL).
Time frame: Up to 52 Weeks
Population: Participants must have both the baseline and at least one post-baseline measurement at the given post-baseline time point to be included in the calculation of the proportion at the given post-baseline time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Achieving a Reduction in the SGRQ Total Score of 4 Points or Greater From Baseline | Week 12 | 50.0 Percent |
| Placebo | Percentage of Participants Achieving a Reduction in the SGRQ Total Score of 4 Points or Greater From Baseline | Week 24 | 63.6 Percent |
| Placebo | Percentage of Participants Achieving a Reduction in the SGRQ Total Score of 4 Points or Greater From Baseline | Week 36 | 57.1 Percent |
| Placebo | Percentage of Participants Achieving a Reduction in the SGRQ Total Score of 4 Points or Greater From Baseline | Week 52 | 68.4 Percent |
| Dupilumab 300 mg Q2W | Percentage of Participants Achieving a Reduction in the SGRQ Total Score of 4 Points or Greater From Baseline | Week 52 | 89.3 Percent |
| Dupilumab 300 mg Q2W | Percentage of Participants Achieving a Reduction in the SGRQ Total Score of 4 Points or Greater From Baseline | Week 12 | 85.3 Percent |
| Dupilumab 300 mg Q2W | Percentage of Participants Achieving a Reduction in the SGRQ Total Score of 4 Points or Greater From Baseline | Week 36 | 86.2 Percent |
| Dupilumab 300 mg Q2W | Percentage of Participants Achieving a Reduction in the SGRQ Total Score of 4 Points or Greater From Baseline | Week 24 | 87.1 Percent |
Secondary
Percent Change From Baseline in A Fumigatus-specific IgE in Serum
Time frame: Over the 24 to 52 Week Treatment Period
Population: Number of randomized patients with a baseline measurement and at least one post-baseline measurement at the post-baseline time point of interest
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in A Fumigatus-specific IgE in Serum | Week 24 | 0.099 Percent | Standard Deviation 39.7612 |
| Placebo | Percent Change From Baseline in A Fumigatus-specific IgE in Serum | Week 36 | 6.766 Percent | Standard Deviation 39.9041 |
| Placebo | Percent Change From Baseline in A Fumigatus-specific IgE in Serum | Week 52 | 12.618 Percent | Standard Deviation 94.6306 |
| Dupilumab 300 mg Q2W | Percent Change From Baseline in A Fumigatus-specific IgE in Serum | Week 24 | -39.859 Percent | Standard Deviation 25.3095 |
| Dupilumab 300 mg Q2W | Percent Change From Baseline in A Fumigatus-specific IgE in Serum | Week 36 | -45.654 Percent | Standard Deviation 26.7915 |
| Dupilumab 300 mg Q2W | Percent Change From Baseline in A Fumigatus-specific IgE in Serum | Week 52 | -49.126 Percent | Standard Deviation 30.679 |
Secondary
Percent Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO)
Time frame: Over the 24 to 52 Week Treatment Period
Population: Number of randomized patients with a baseline measurement and at least one post-baseline measurement at the post-baseline time point of interest
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) | Week 24 | 1.67 Percent | Standard Deviation 44.069 |
| Placebo | Percent Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) | Week 36 | 19.80 Percent | Standard Deviation 44.053 |
| Placebo | Percent Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) | Week 44 | 15.43 Percent | Standard Deviation 54.887 |
| Placebo | Percent Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) | Week 52 | 2.55 Percent | Standard Deviation 56.506 |
| Dupilumab 300 mg Q2W | Percent Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) | Week 52 | -20.35 Percent | Standard Deviation 48.1 |
| Dupilumab 300 mg Q2W | Percent Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) | Week 24 | -29.91 Percent | Standard Deviation 32.527 |
| Dupilumab 300 mg Q2W | Percent Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) | Week 44 | -19.83 Percent | Standard Deviation 48.308 |
| Dupilumab 300 mg Q2W | Percent Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) | Week 36 | -24.56 Percent | Standard Deviation 43.975 |
Secondary
Percent Change From Baseline in Total IgE in Serum
Time frame: Over the 24 to 52 Week Treatment Period
Population: Number of randomized patients with a baseline measurement and at least one post-baseline measurement at the post-baseline time point of interest
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline in Total IgE in Serum | Week 24 | -0.665 Percent | Standard Deviation 40.2236 |
| Placebo | Percent Change From Baseline in Total IgE in Serum | Week 36 | -5.945 Percent | Standard Deviation 27.6767 |
| Placebo | Percent Change From Baseline in Total IgE in Serum | Week 52 | -2.767 Percent | Standard Deviation 42.8914 |
| Dupilumab 300 mg Q2W | Percent Change From Baseline in Total IgE in Serum | Week 24 | -47.245 Percent | Standard Deviation 19.411 |
| Dupilumab 300 mg Q2W | Percent Change From Baseline in Total IgE in Serum | Week 36 | -57.752 Percent | Standard Deviation 18.0812 |
| Dupilumab 300 mg Q2W | Percent Change From Baseline in Total IgE in Serum | Week 52 | -62.175 Percent | Standard Deviation 17.0285 |