Allergic Rhinitis
Conditions
Brief summary
The primary objective is to assess whether 16 weeks of treatment with dupilumab as an adjunct to Timothy Grass Subcutaneous Immunotherapy (SCIT) improves upon the efficacy of Timothy Grass SCIT to reduce provoked allergic rhinitis symptoms, as measured by Total Nasal Symptom Score (TNSS) after nasal allergen challenge (NAC) with Timothy Grass extract at week 17. The secondary objectives of the study are: * To assess whether 16 weeks of treatment with dupilumab as compared to placebo reduces provoked allergic rhinitis symptoms, as measured by TNSS after nasal allergen challenge (NAC) with Timothy Grass extract * To assess whether 16 weeks of treatment with dupilumab as compared to dupilumab + SCIT reduces provoked allergic rhinitis symptoms, as measured by TNSS after nasal allergen challenge (NAC) with Timothy Grass extract * To assess changes in serum Timothy-grass-specific immunoglobulin G4 (IgG4), serum Timothy grass-specific immunoglobulin E (IgE), and ratio of serum Timothy Grass-specific IgG4 to IgE over 16 weeks of treatment with dupilumab + SCIT as compared to SCIT monotherapy * To evaluate the safety and tolerability of 16 weeks of treatment with dupilumab as an adjunct to Timothy Grass SCIT
Interventions
DRUGDupilumab
Dupilumab was administered SC in a single-use, pre-filled glass syringe
DRUGTimothy Grass SCIT
Timothy grass extract was administered SC.
Placebo matching dupilumab was prepared in the same formulation without the addition of protein
DRUGPlacebo matching SCIT
Placebo matching SCIT was prepared in the same formulation (SCIT diluent) without the addition of Timothy grass extract
Sponsors
Sanofi
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Male and female participants aged 18 to 55 2. History of grass pollen-induced seasonal allergic rhinitis 3. Grass pollen allergy confirmed by both: 1. Positive skin prick test (SPT) with Timothy Grass extract (mean wheal diameter at least ≥5 mm greater than a negative control) 2. Positive serum Timothy Grass-specific IgE (≥0.35KU/L) Key
Exclusion criteria
1. Significant rhinitis, sinusitis, outside of the grass pollen season 2. Any contraindications to SCIT (i.e, severe cardiovascular disease, malignancies, autoimmune disease, use of beta blocker, asthma severe enough to require chronic medication, acute infection) 3. Use of systemic corticosteroids within 4 weeks of screening visits or any NAC visits 4. Abnormal lung function as judged by the investigator 5. A clinical history of asthma requiring chronic medication such as regular inhaled corticosteroids for \>4 weeks per year 6. History of significant recurrent sinusitis, defined as 3 episodes per year for the last 2 years, all of which required antibiotic treatment 7. History of chronic sinusitis (with or without nasal polyps) 8. Tobacco smoking (ANY) within the last year Note: Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Total Nasal Symptom Score (TNSS) Area Under Curve (AUC) (0-1 Hour (hr) Post Peak TNSS) in Response to Post Nasal Allergen Challenge (NAC) at Week 17 | Baseline, Week 17 | TNSS was participant-reported composite symptom assessment of 4 symptoms (rhinorrhea, nasal congestion, nasal itching & sneezing), each scored on a scale from 0 to 3 where 0 = none, 3 = severe. TNSS total score was calculated as the sum of the response for all 4 individual nasal symptom scores and ranged from 0 to 12, where higher score indicated more severe symptoms. AUC of TNSS/component from time of the first observation to time of the last observation (AUC \[0-1 hr\]) was calculated by using the trapezoid rule. Data was reported for Dupilumab + SCIT and placebo matched to Dupilumab + SCIT monotherapy group in this outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Nasal Symptom Score (TNSS) Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour After the Challenge (0-1 Hour (hr) Post Peak TNSS) at Week 17 in Placebo vs. Dupilumab | Baseline, Week 17 | TNSS was participant-reported composite symptom assessment of 4 symptoms (rhinorrhea, nasal congestion, nasal itching & sneezing) each scored on a scale from 0 to 3 where 0 = none, 3 = severe. TNSS total score was calculated as the sum of the response for all 4 individual nasal symptom scores and ranged from 0 to 12, where higher score indicated more severe symptoms. AUC of TNSS/component from time of the first observation to time of the last observation (AUC \[0-1 hr\]) was calculated by using the trapezoid rule. Data was reported for Dupilumab + placebo matched to SCIT and placebo matched to dupilumab + placebo matched to SCIT group in this outcome measure. |
| Percent Change From Baseline in Total Nasal Symptom Score (TNSS) Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour of the Challenge (0-1 Hour (hr) Post Peak TNSS) at Week 17 | Baseline, Week 17 | TNSS was participant-reported composite symptom assessment of 4 symptoms (rhinorrhea, nasal congestion, nasal itching & sneezing) each scored on a scale from 0 to 3 where 0 = none, 3 = severe. TNSS total score was calculated as the sum of the response for all 4 individual nasal symptom scores and ranged from 0 to 12, where higher score indicated more severe symptoms. AUC of TNSS/component from time of the first observation to time of the last observation (AUC \[0-1 hr\]) was calculated by using the trapezoid rule. Data was reported for Dupilumab + placebo matched to SCIT and placebo matched to dupilumab + placebo matched to SCIT. |
| Change From Baseline in TNSS Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour of the Challenge (0-1 Hour (hr) Post Peak TNSS) at Week 17 | Baseline, Week 17 | TNSS was participant-reported composite symptom assessment of 4 symptoms (rhinorrhea, nasal congestion, nasal itching & sneezing) each scored on a scale from 0 to 3 where 0 = none, 3 = severe. TNSS total score was calculated as the sum of responses for all 4 individual nasal symptom scores and ranged from 0 to 12, where higher score indicated more severe symptoms. AUC of TNSS/component from time of the first observation to time of the last observation (AUC \[0-1 hr\]) was calculated by using the trapezoid rule. Data was reported for Dupilumab + SCIT and Dupilumab + placebo matched to SCIT group in this outcome measure. |
| Percent Change From Baseline in TNSS Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour of the Challenge (0-1 Hour (hr) Post Peak TNSS) at Week 17 | Baseline, Week 17 | TNSS was participant-reported composite symptom assessment of 4 symptoms (rhinorrhea, nasal congestion, nasal itching & sneezing) each scored on a scale from 0 to 3 where 0 = none, 3 = severe. TNSS total score was calculated as the sum of the response for all 4 individual nasal symptom scores and ranged from 0 to 12, where higher score indicated more severe symptoms. AUC of TNSS/component from time of the first observation to time of the last observation (AUC \[0-1 hr\]) was calculated by using the trapezoid rule. Data was reported for Dupilumab + SCIT and Dupilumab + placebo matched to SCIT group in this outcome measure. |
| Change From Baseline in Serum Timothy Grass Specific Immunoglobulin G4 (sIgG4) to Week 17 | Baseline, Week 17 | Measurement of Timothy Grass specific IgG4 was performed in serum or plasma to determine effects on biomarkers of relevant physiological and pathogenic processes. Data was reported for Dupilumab + SCIT and placebo matched to Dupilumab + SCIT monotherapy group in this outcome measure. Missing values were imputed by Last Observation Carried Forward (LOCF) method for visits between post-baseline to Week 17. |
| Change From Baseline in Total Nasal Symptom Score (TNSS) Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour After the Challenge (0-1 Hour (hr) Post Peak TNSS) at Week 17 in SCIT vs. Dupilumab + SCIT | Baseline, Week 17 | TNSS was participant-reported composite symptom assessment of 4 symptoms (rhinorrhea, nasal congestion, nasal itching & sneezing) each scored on a scale from 0 to 3 where 0 = none, 3 = severe. TNSS total score was calculated as the sum of the response for all 4 individual nasal symptom scores and ranged from 0 to 12, where higher score indicated more severe symptoms. AUC of TNSS/component from time of the first observation to time of the last observation (AUC \[0-1 hr\]) was calculated by using the trapezoid rule. Data was reported for Dupilumab + SCIT and placebo matched to Dupilumab + SCIT monotherapy group in this outcome measure. |
| Change From Baseline in Serum Timothy Grass Specific Immunoglobulin E (sIgE) to Week 17 | Baseline, Week 17 | Measurement of Timothy Grass specific sIgE was performed in serum or plasma to determine effects on biomarkers of relevant physiological and pathogenic processes. Data was reported for Dupilumab + SCIT and placebo matched to Dupilumab + SCIT monotherapy group in this outcome measure. Missing value was imputed by LOCF method for visits between post-baseline to Week 17. |
| Percent Change From Baseline in Serum Timothy Grass Specific Immunoglobulin E (sIgE) to Week 17 | Baseline, Week 17 | Measurement of Timothy Grass specific sIgE was performed in serum or plasma to determine effects on biomarkers of relevant physiological and pathogenic processes. Data was reported for Dupilumab + SCIT and placebo matched to Dupilumab + SCIT monotherapy group in this outcome measure. Missing value was imputed by LOCF method for visits between post-baseline to Week 17. |
| Change From Baseline in Log-Transformed Value of Serum Timothy Grass Specific Immunoglobulin G4 (sIgG4) to Serum Timothy Grass Specific Immunoglobulin E (sIgE) Ratio to Week 17 | Baseline, Week 17 | Biomarkers measured in serum or plasma to determine effects on biomarkers of relevant physiological and pathogenic processes. Data was reported for Dupilumab + SCIT and placebo matched to Dupilumab + SCIT monotherapy group in this outcome measure. Missing value was imputed by LOCF method for visits between post-baseline to Week 17. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Baseline through Week 24 | Treatment-emergent adverse events (TEAEs) were defined as adverse events (AEs) that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to the end of study \[Week 24\]). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-participant hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. |
| Percent Change From Baseline in Serum Timothy Grass Specific Immunoglobulin G4 (sIgG4) to Week 17 | Baseline, Week 17 | Measurement of Timothy Grass specific IgG4 was performed in serum or plasma to determine effects on biomarkers of relevant physiological and pathogenic processes. Data was for Dupilumab + SCIT and placebo matched to Dupilumab + SCIT monotherapy group in this outcome measure. Missing value was imputed by LOCF method for visits between post-baseline to Week 17. |
Countries
Canada, United States
Participant flow
Recruitment details
A total of 214 participants were screened for study eligibility at 17 study sites in United States and Canada, of whom 103 were randomized to receive the study treatment. Screen failure was mostly due to inclusion criteria not met/exclusion criteria met.
Pre-assignment details
Participants who met the eligibility criteria were randomized in 1:1:1:1 ratio to 1 of 4 treatment groups: Placebo, Dupilumab, Subcutaneous immunotherapy (SCIT) and Dupilumab + SCIT.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo matched to Dupilumab and placebo matched to Timothy grass subcutaneous immunotherapy (SCIT) every 2 weeks (Q2W) for 16 weeks. Both placebo doses were administered with a gap of 1 to 7 days. | 25 |
| Dupilumab Participants received placebo matched to SCIT and subcutaneous (SC) injections of Dupilumab at a loading dose of 600 milligrams (mg) on Day 1, followed by a 300 mg for Q2W for 16 weeks. Both placebo matched to SCIT and Dupilumab doses were administered with a gap of 1 to 7 days. | 26 |
| SCIT Participants received SCIT titrated up to a 4000 bioequivalent allergy unit (BAU) for 8 weeks followed by maintenance dose of 4000 BAU for following 8 weeks and SC injections of placebo matched to Dupilumab Q2W for 16 weeks. Both SCIT and placebo matched to Dupilumab doses were administered with a gap of 1 to 7 days. | 26 |
| Dupilumab + SCIT Participants received SC injections of Dupilumab at a loading dose of 600 mg on Day 1, followed by 300 mg Q2W for 16 weeks and SCIT titrated up to 4000 BAU for 8 weeks followed by maintenance dose of 4000 BAU for following 8 weeks. Both SCIT and Dupilumab doses were administered with a gap of 1 to 7 days. | 26 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 5 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | SCIT | Placebo | Dupilumab + SCIT | Total | Dupilumab |
|---|---|---|---|---|---|
| Age, Continuous | 37.8 Years STANDARD_DEVIATION 11.25 | 34.6 Years STANDARD_DEVIATION 11.05 | 33.0 Years STANDARD_DEVIATION 10.58 | 36.5 Years STANDARD_DEVIATION 11.22 | 40.3 Years STANDARD_DEVIATION 11.19 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 3 Participants | 1 Participants | 11 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 21 Participants | 25 Participants | 91 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Log Transformed Timothy Grass Pollen IgG4 vs sIgE ratio | -1.860 Ratio | -1.970 Ratio | -1.975 Ratio | -1.840 Ratio | -1.515 Ratio |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 2 Participants | 2 Participants | 9 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 2 Participants | 2 Participants | 12 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 20 Participants | 21 Participants | 76 Participants | 18 Participants |
| Sex: Female, Male Female | 14 Participants | 10 Participants | 10 Participants | 50 Participants | 16 Participants |
| Sex: Female, Male Male | 12 Participants | 15 Participants | 16 Participants | 53 Participants | 10 Participants |
| Timothy Grass Pollen IgG4 | 0.080 Miligram per Liter (mg/L) | 0.080 Miligram per Liter (mg/L) | 0.080 Miligram per Liter (mg/L) | 0.080 Miligram per Liter (mg/L) | 0.080 Miligram per Liter (mg/L) |
| Timothy Grass Specific Immunoglobulin E (sIgE) | 10.300 Kilo Unit per Liter (kU/L) | 9.640 Kilo Unit per Liter (kU/L) | 11.250 Kilo Unit per Liter (kU/L) | 9.180 Kilo Unit per Liter (kU/L) | 4.810 Kilo Unit per Liter (kU/L) |
| Total nasal symptom score (TNSS) Area under Curve (AUC) [0-1 hour (hr)] at Baseline | 4.66 Score on a Scale*hour STANDARD_DEVIATION 1.987 | 5.34 Score on a Scale*hour STANDARD_DEVIATION 2.175 | 4.69 Score on a Scale*hour STANDARD_DEVIATION 1.72 | 4.93 Score on a Scale*hour STANDARD_DEVIATION 2.015 | 5.03 Score on a Scale*hour STANDARD_DEVIATION 2.193 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 26 | 0 / 26 | 0 / 26 |
| other Total, other adverse events | 19 / 25 | 16 / 26 | 23 / 26 | 20 / 26 |
| serious Total, serious adverse events | 1 / 25 | 1 / 26 | 1 / 26 | 2 / 26 |
Outcome results
Primary
Percent Change From Baseline in Total Nasal Symptom Score (TNSS) Area Under Curve (AUC) (0-1 Hour (hr) Post Peak TNSS) in Response to Post Nasal Allergen Challenge (NAC) at Week 17
TNSS was participant-reported composite symptom assessment of 4 symptoms (rhinorrhea, nasal congestion, nasal itching & sneezing), each scored on a scale from 0 to 3 where 0 = none, 3 = severe. TNSS total score was calculated as the sum of the response for all 4 individual nasal symptom scores and ranged from 0 to 12, where higher score indicated more severe symptoms. AUC of TNSS/component from time of the first observation to time of the last observation (AUC \[0-1 hr\]) was calculated by using the trapezoid rule. Data was reported for Dupilumab + SCIT and placebo matched to Dupilumab + SCIT monotherapy group in this outcome measure.
Time frame: Baseline, Week 17
Population: The full analysis set (FAS) included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SCIT | Percent Change From Baseline in Total Nasal Symptom Score (TNSS) Area Under Curve (AUC) (0-1 Hour (hr) Post Peak TNSS) in Response to Post Nasal Allergen Challenge (NAC) at Week 17 | -56.76 Percent Change | Standard Error 9.687 |
| Dupilumab + SCIT | Percent Change From Baseline in Total Nasal Symptom Score (TNSS) Area Under Curve (AUC) (0-1 Hour (hr) Post Peak TNSS) in Response to Post Nasal Allergen Challenge (NAC) at Week 17 | -52.03 Percent Change | Standard Error 8.462 |
p-value: 0.718595% CI: [-21.023, 30.487]ANCOVA
Secondary
Change From Baseline in Log-Transformed Value of Serum Timothy Grass Specific Immunoglobulin G4 (sIgG4) to Serum Timothy Grass Specific Immunoglobulin E (sIgE) Ratio to Week 17
Biomarkers measured in serum or plasma to determine effects on biomarkers of relevant physiological and pathogenic processes. Data was reported for Dupilumab + SCIT and placebo matched to Dupilumab + SCIT monotherapy group in this outcome measure. Missing value was imputed by LOCF method for visits between post-baseline to Week 17.
Time frame: Baseline, Week 17
Population: FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SCIT | Change From Baseline in Log-Transformed Value of Serum Timothy Grass Specific Immunoglobulin G4 (sIgG4) to Serum Timothy Grass Specific Immunoglobulin E (sIgE) Ratio to Week 17 | 0.745 Ratio |
| Dupilumab + SCIT | Change From Baseline in Log-Transformed Value of Serum Timothy Grass Specific Immunoglobulin G4 (sIgG4) to Serum Timothy Grass Specific Immunoglobulin E (sIgE) Ratio to Week 17 | 1.720 Ratio |
p-value: <0.000195% CI: [0.45, 1.27]ANCOVA
Secondary
Change From Baseline in Serum Timothy Grass Specific Immunoglobulin E (sIgE) to Week 17
Measurement of Timothy Grass specific sIgE was performed in serum or plasma to determine effects on biomarkers of relevant physiological and pathogenic processes. Data was reported for Dupilumab + SCIT and placebo matched to Dupilumab + SCIT monotherapy group in this outcome measure. Missing value was imputed by LOCF method for visits between post-baseline to Week 17.
Time frame: Baseline, Week 17
Population: FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SCIT | Change From Baseline in Serum Timothy Grass Specific Immunoglobulin E (sIgE) to Week 17 | 6.460 Kilo Unit per Liter (kU/L) |
| Dupilumab + SCIT | Change From Baseline in Serum Timothy Grass Specific Immunoglobulin E (sIgE) to Week 17 | -2.990 Kilo Unit per Liter (kU/L) |
p-value: <0.000195% CI: [-23.94, -8.36]ANCOVA
Secondary
Change From Baseline in Serum Timothy Grass Specific Immunoglobulin G4 (sIgG4) to Week 17
Measurement of Timothy Grass specific IgG4 was performed in serum or plasma to determine effects on biomarkers of relevant physiological and pathogenic processes. Data was reported for Dupilumab + SCIT and placebo matched to Dupilumab + SCIT monotherapy group in this outcome measure. Missing values were imputed by Last Observation Carried Forward (LOCF) method for visits between post-baseline to Week 17.
Time frame: Baseline, Week 17
Population: FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SCIT | Change From Baseline in Serum Timothy Grass Specific Immunoglobulin G4 (sIgG4) to Week 17 | 1.705 Milligram per Liter (mg/L) |
| Dupilumab + SCIT | Change From Baseline in Serum Timothy Grass Specific Immunoglobulin G4 (sIgG4) to Week 17 | 3.550 Milligram per Liter (mg/L) |
p-value: 0.144995% CI: [-0.77, 3.21]ANCOVA
Secondary
Change From Baseline in TNSS Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour of the Challenge (0-1 Hour (hr) Post Peak TNSS) at Week 17
TNSS was participant-reported composite symptom assessment of 4 symptoms (rhinorrhea, nasal congestion, nasal itching & sneezing) each scored on a scale from 0 to 3 where 0 = none, 3 = severe. TNSS total score was calculated as the sum of responses for all 4 individual nasal symptom scores and ranged from 0 to 12, where higher score indicated more severe symptoms. AUC of TNSS/component from time of the first observation to time of the last observation (AUC \[0-1 hr\]) was calculated by using the trapezoid rule. Data was reported for Dupilumab + SCIT and Dupilumab + placebo matched to SCIT group in this outcome measure.
Time frame: Baseline, Week 17
Population: FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SCIT | Change From Baseline in TNSS Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour of the Challenge (0-1 Hour (hr) Post Peak TNSS) at Week 17 | -1.83 Score on a Scale*hour | Standard Error 0.329 |
| Dupilumab + SCIT | Change From Baseline in TNSS Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour of the Challenge (0-1 Hour (hr) Post Peak TNSS) at Week 17 | -2.77 Score on a Scale*hour | Standard Error 0.321 |
p-value: 0.041495% CI: [-1.848, -0.037]ANCOVA
Secondary
Change From Baseline in Total Nasal Symptom Score (TNSS) Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour After the Challenge (0-1 Hour (hr) Post Peak TNSS) at Week 17 in Placebo vs. Dupilumab
TNSS was participant-reported composite symptom assessment of 4 symptoms (rhinorrhea, nasal congestion, nasal itching & sneezing) each scored on a scale from 0 to 3 where 0 = none, 3 = severe. TNSS total score was calculated as the sum of the response for all 4 individual nasal symptom scores and ranged from 0 to 12, where higher score indicated more severe symptoms. AUC of TNSS/component from time of the first observation to time of the last observation (AUC \[0-1 hr\]) was calculated by using the trapezoid rule. Data was reported for Dupilumab + placebo matched to SCIT and placebo matched to dupilumab + placebo matched to SCIT group in this outcome measure.
Time frame: Baseline, Week 17
Population: FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SCIT | Change From Baseline in Total Nasal Symptom Score (TNSS) Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour After the Challenge (0-1 Hour (hr) Post Peak TNSS) at Week 17 in Placebo vs. Dupilumab | -1.85 Score on a Scale*hour | Standard Error 0.323 |
| Dupilumab + SCIT | Change From Baseline in Total Nasal Symptom Score (TNSS) Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour After the Challenge (0-1 Hour (hr) Post Peak TNSS) at Week 17 in Placebo vs. Dupilumab | -1.83 Score on a Scale*hour | Standard Error 0.329 |
p-value: 0.955995% CI: [-0.877, 0.928]ANCOVA
Secondary
Change From Baseline in Total Nasal Symptom Score (TNSS) Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour After the Challenge (0-1 Hour (hr) Post Peak TNSS) at Week 17 in SCIT vs. Dupilumab + SCIT
TNSS was participant-reported composite symptom assessment of 4 symptoms (rhinorrhea, nasal congestion, nasal itching & sneezing) each scored on a scale from 0 to 3 where 0 = none, 3 = severe. TNSS total score was calculated as the sum of the response for all 4 individual nasal symptom scores and ranged from 0 to 12, where higher score indicated more severe symptoms. AUC of TNSS/component from time of the first observation to time of the last observation (AUC \[0-1 hr\]) was calculated by using the trapezoid rule. Data was reported for Dupilumab + SCIT and placebo matched to Dupilumab + SCIT monotherapy group in this outcome measure.
Time frame: Baseline, Week 17
Population: FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SCIT | Change From Baseline in Total Nasal Symptom Score (TNSS) Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour After the Challenge (0-1 Hour (hr) Post Peak TNSS) at Week 17 in SCIT vs. Dupilumab + SCIT | -3.07 Score on a Scale*hour | Standard Error 0.361 |
| Dupilumab + SCIT | Change From Baseline in Total Nasal Symptom Score (TNSS) Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour After the Challenge (0-1 Hour (hr) Post Peak TNSS) at Week 17 in SCIT vs. Dupilumab + SCIT | -2.77 Score on a Scale*hour | Standard Error 0.321 |
p-value: 0.543895% CI: [-0.661, 1.254]ANCOVA
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Treatment-emergent adverse events (TEAEs) were defined as adverse events (AEs) that developed or worsened or became serious during on-treatment period (time from the first dose of study drug up to the end of study \[Week 24\]). A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-participant hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.
Time frame: Baseline through Week 24
Population: The safety analysis set (SAF) included all randomized participants who received at least one injection of study drug, it was based on the treatment received (as treated).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SCIT | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 21 Participants |
| SCIT | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 1 Participants |
| Dupilumab + SCIT | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 1 Participants |
| Dupilumab + SCIT | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 18 Participants |
| SCIT | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 24 Participants |
| SCIT | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 1 Participants |
| Dupilumab + SCIT | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 22 Participants |
| Dupilumab + SCIT | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 2 Participants |
Secondary
Percent Change From Baseline in Serum Timothy Grass Specific Immunoglobulin E (sIgE) to Week 17
Measurement of Timothy Grass specific sIgE was performed in serum or plasma to determine effects on biomarkers of relevant physiological and pathogenic processes. Data was reported for Dupilumab + SCIT and placebo matched to Dupilumab + SCIT monotherapy group in this outcome measure. Missing value was imputed by LOCF method for visits between post-baseline to Week 17.
Time frame: Baseline, Week 17
Population: FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SCIT | Percent Change From Baseline in Serum Timothy Grass Specific Immunoglobulin E (sIgE) to Week 17 | 81.27 Percent Change |
| Dupilumab + SCIT | Percent Change From Baseline in Serum Timothy Grass Specific Immunoglobulin E (sIgE) to Week 17 | -56.44 Percent Change |
p-value: <0.000195% CI: [-205.51, -94.98]ANCOVA
Secondary
Percent Change From Baseline in Serum Timothy Grass Specific Immunoglobulin G4 (sIgG4) to Week 17
Measurement of Timothy Grass specific IgG4 was performed in serum or plasma to determine effects on biomarkers of relevant physiological and pathogenic processes. Data was for Dupilumab + SCIT and placebo matched to Dupilumab + SCIT monotherapy group in this outcome measure. Missing value was imputed by LOCF method for visits between post-baseline to Week 17.
Time frame: Baseline, Week 17
Population: FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SCIT | Percent Change From Baseline in Serum Timothy Grass Specific Immunoglobulin G4 (sIgG4) to Week 17 | 1444.49 Percent Change |
| Dupilumab + SCIT | Percent Change From Baseline in Serum Timothy Grass Specific Immunoglobulin G4 (sIgG4) to Week 17 | 1896.25 Percent Change |
p-value: 0.123195% CI: [-551.47, 1746.55]ANCOVA
Secondary
Percent Change From Baseline in TNSS Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour of the Challenge (0-1 Hour (hr) Post Peak TNSS) at Week 17
TNSS was participant-reported composite symptom assessment of 4 symptoms (rhinorrhea, nasal congestion, nasal itching & sneezing) each scored on a scale from 0 to 3 where 0 = none, 3 = severe. TNSS total score was calculated as the sum of the response for all 4 individual nasal symptom scores and ranged from 0 to 12, where higher score indicated more severe symptoms. AUC of TNSS/component from time of the first observation to time of the last observation (AUC \[0-1 hr\]) was calculated by using the trapezoid rule. Data was reported for Dupilumab + SCIT and Dupilumab + placebo matched to SCIT group in this outcome measure.
Time frame: Baseline, Week 17
Population: FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SCIT | Percent Change From Baseline in TNSS Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour of the Challenge (0-1 Hour (hr) Post Peak TNSS) at Week 17 | -21.57 Percent Change | Standard Error 8.415 |
| Dupilumab + SCIT | Percent Change From Baseline in TNSS Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour of the Challenge (0-1 Hour (hr) Post Peak TNSS) at Week 17 | -52.03 Percent Change | Standard Error 8.462 |
p-value: 0.010895% CI: [-53.874, -7.034]ANCOVA
Secondary
Percent Change From Baseline in Total Nasal Symptom Score (TNSS) Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour of the Challenge (0-1 Hour (hr) Post Peak TNSS) at Week 17
TNSS was participant-reported composite symptom assessment of 4 symptoms (rhinorrhea, nasal congestion, nasal itching & sneezing) each scored on a scale from 0 to 3 where 0 = none, 3 = severe. TNSS total score was calculated as the sum of the response for all 4 individual nasal symptom scores and ranged from 0 to 12, where higher score indicated more severe symptoms. AUC of TNSS/component from time of the first observation to time of the last observation (AUC \[0-1 hr\]) was calculated by using the trapezoid rule. Data was reported for Dupilumab + placebo matched to SCIT and placebo matched to dupilumab + placebo matched to SCIT.
Time frame: Baseline, Week 17
Population: FAS included all randomized participants. Efficacy analyses were based on the treatment allocated at randomization (as randomized).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SCIT | Percent Change From Baseline in Total Nasal Symptom Score (TNSS) Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour of the Challenge (0-1 Hour (hr) Post Peak TNSS) at Week 17 | -28.82 Percent Change | Standard Error 8.427 |
| Dupilumab + SCIT | Percent Change From Baseline in Total Nasal Symptom Score (TNSS) Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour of the Challenge (0-1 Hour (hr) Post Peak TNSS) at Week 17 | -21.57 Percent Change | Standard Error 8.415 |
p-value: 0.541695% CI: [-16.028, 30.53]ANCOVA