Dupilumab As An Adjunct For Subcutaneous Grass Immunotherapy

Allergic Rhinitis Clinical Trial

Official title:

A Study To Evaluate The Efficacy Of Dupilumab As An Adjunct For Subcutaneous Grass Immunotherapy To Reduce Provoked Allergic Rhinitis Symptoms Using The Nasal Allergen Challenge Model

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03558997
• Other study ID #: R668-ALG-16115
• Status: Completed
• Phase: Phase 2
• Start date: June 7, 2018
• Est. completion date: June 13, 2019

Study information

• Verified date: May 2020
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 103
• Est. completion date: June 13, 2019
• Est. primary completion date: May 14, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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/ exclusion criteria apply

Related Conditions & MeSH terms

• Allergic Rhinitis
• Rhinitis
• Rhinitis, Allergic

Intervention

Drug:
• Dupilumab
Dupilumab was administered SC in a single-use, pre-filled glass syringe
• Timothy Grass SCIT
Timothy grass extract was administered SC.
• Placebo matching dupilumab
Placebo matching dupilumab was prepared in the same formulation without the addition of protein
• Placebo matching SCIT
Placebo matching SCIT was prepared in the same formulation (SCIT diluent) without the addition of Timothy grass extract

Locations

Country	Name	City	State
Canada	Regeneron Investigational Site	Kingston	Ontario
Canada	Regeneron Investigational Site	Mississauga	Ontario
Canada	Regeneron Investigational Site	Ottawa	Ontario
Canada	Regeneron Investigational Site	Québec	Quebec
Canada	Regeneron Investigational Site	Toronto	Ontario
United States	Regeneron Investigational Site	Andover	Massachusetts
United States	Regeneron Investigational Site	Baltimore	Maryland
United States	Regeneron Investigational Site	Bellevue	Nebraska
United States	Regeneron Investigational Site	East Providence	Rhode Island
United States	Regeneron Investigational Site	Los Angeles	California
United States	Regeneron Investigational Site	Madison	Wisconsin
United States	Regeneron Investigational Site	Mountain View	California
United States	Regeneron Investigational Site	North Dartmouth	Massachusetts
United States	Regeneron Investigational Site	Portland	Oregon
United States	Regeneron Investigational Site	Saint Louis	Missouri
United States	Regeneron Investigational Site	Seattle	Washington
United States	Regeneron Investigational Site	Walnut Creek	California

Sponsors (2)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals	Sanofi

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline, Week 17
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.	Baseline, Week 17
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.	Baseline, Week 17
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.	Baseline, Week 17
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.	Baseline, Week 17
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.	Baseline, Week 17
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.	Baseline, Week 17
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.	Baseline, Week 17
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.	Baseline, Week 17
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.	Baseline, Week 17
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.	Baseline, Week 17
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.	Baseline through Week 24