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Completed

NCT Number: NCT03558997

Dupilumab As An Adjunct For Subcutaneous Grass Immunotherapy

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

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Key information

Conditions

Allergic Rhinitis Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Nose Diseases Otorhinolaryngologic Diseases Respiratory Hypersensitivity Respiratory Tract Diseases Rhinitis Rhinitis, Allergic

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Regeneron Investigational Site, Kingston, Ontario, Canada

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • Male and female participants aged 18 to 55
  • History of grass pollen-induced seasonal allergic rhinitis
  • Grass pollen allergy confirmed by both:
  • Positive skin prick test (SPT) with Timothy Grass extract (mean wheal diameter at least ≥5 mm greater than a negative control)
  • Positive serum Timothy Grass-specific IgE (≥0.35KU/L)

Key Exclusion Criteria:

  • Significant rhinitis, sinusitis, outside of the grass pollen season
  • 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)
  • Use of systemic corticosteroids within 4 weeks of screening visits or any NAC visits
  • Abnormal lung function as judged by the investigator
  • A clinical history of asthma requiring chronic medication such as regular inhaled corticosteroids for >4 weeks per year
  • History of significant recurrent sinusitis, defined as 3 episodes per year for the last 2 years, all of which required antibiotic treatment
  • History of chronic sinusitis (with or without nasal polyps)
  • Tobacco smoking (ANY) within the last year

Note: Other protocol defined inclusion/ exclusion criteria apply

Treatment and study plan

Dupilumab

Drug

Dupilumab was administered SC in a single-use, pre-filled glass syringe

Other names: DUPIXENT®, REGN668, SAR231893

Timothy Grass SCIT

Drug

Timothy grass extract was administered SC.

Placebo matching dupilumab

Drug

Placebo matching dupilumab was prepared in the same formulation without the addition of protein

Placebo matching SCIT

Drug

Placebo matching SCIT was prepared in the same formulation (SCIT diluent) without the addition of Timothy grass extract

Primary outcomes

  1. 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

    Time frame: 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 outcomes

  1. 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

    Time frame: 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.

  2. 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

    Time frame: 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.

  3. 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

    Time frame: 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.

  4. 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

    Time frame: 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.

  5. 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

    Time frame: 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.

  6. Change From Baseline in Serum Timothy Grass Specific Immunoglobulin G4 (sIgG4) to Week 17

    Time frame: 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.

  7. Percent Change From Baseline in Serum Timothy Grass Specific Immunoglobulin G4 (sIgG4) to Week 17

    Time frame: 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.

  8. Change From Baseline in Serum Timothy Grass Specific Immunoglobulin E (sIgE) to Week 17

    Time frame: 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.

  9. Percent Change From Baseline in Serum Timothy Grass Specific Immunoglobulin E (sIgE) to Week 17

    Time frame: 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.

  10. 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

    Time frame: 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.

  11. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Regeneron Pharmaceuticals

Industry

Collaborators

  • Sanofi

Registry information

Official study 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

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Jun 15, 2018
Registry last updated
May 28, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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