Dupilumab As An Adjunct For Subcutaneous Grass Immunotherapy

May 11, 2020 updated by: Regeneron Pharmaceuticals

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

103

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Kingston, Ontario, Canada, K7L 2V7
        • Regeneron Investigational Site
      • Mississauga, Ontario, Canada, L5A 3V4
        • Regeneron Investigational Site
      • Ottawa, Ontario, Canada, K1G 6C6
        • Regeneron Investigational Site
      • Toronto, Ontario, Canada, M4V 1R2
        • Regeneron Investigational Site
    • Quebec
      • Québec, Quebec, Canada, G1V 4W2
        • Regeneron Investigational Site
  • United States
    • California
      • Los Angeles, California, United States, 90025
        • Regeneron Investigational Site
      • Mountain View, California, United States, 94040
        • Regeneron Investigational Site
      • Walnut Creek, California, United States, 94598
        • Regeneron Investigational Site
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Regeneron Investigational Site
    • Massachusetts
      • Andover, Massachusetts, United States, 01810
        • Regeneron Investigational Site
      • North Dartmouth, Massachusetts, United States, 02747
        • Regeneron Investigational Site
    • Missouri
      • Saint Louis, Missouri, United States, 63141
        • Regeneron Investigational Site
    • Nebraska
      • Bellevue, Nebraska, United States, 68123
        • Regeneron Investigational Site
    • Oregon
      • Portland, Oregon, United States, 97202
        • Regeneron Investigational Site
    • Rhode Island
      • East Providence, Rhode Island, United States, 02914
        • Regeneron Investigational Site
    • Washington
      • Seattle, Washington, United States, 98115
        • Regeneron Investigational Site
    • Wisconsin
      • Madison, Wisconsin, United States, 53792-9988
        • Regeneron Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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 or 7 days.
Drug: Placebo matching dupilumab
Placebo matching dupilumab was prepared in the same formulation without the addition of protein
Drug: Placebo matching SCIT
Placebo matching SCIT was prepared in the same formulation (SCIT diluent) without the addition of Timothy grass extract
Experimental: 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 or 7 days.
Drug: Placebo matching SCIT
Placebo matching SCIT was prepared in the same formulation (SCIT diluent) without the addition of Timothy grass extract
Drug: Dupilumab
Dupilumab was administered SC in a single-use, pre-filled glass syringe
Other Names:
  • REGN668
  • SAR231893
  • DUPIXENT®
Experimental: 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 or 7 days.
Drug: Placebo matching dupilumab
Placebo matching dupilumab was prepared in the same formulation without the addition of protein
Drug: Timothy Grass SCIT
Timothy grass extract was administered SC.
Experimental: 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 or 7 days.
Drug: Dupilumab
Dupilumab was administered SC in a single-use, pre-filled glass syringe
Other Names:
  • REGN668
  • SAR231893
  • DUPIXENT®
Drug: Timothy Grass SCIT
Timothy grass extract was administered SC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline, Week 17

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline, 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 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.
Baseline, Week 17
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.
Baseline, Week 17
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.
Baseline, Week 17
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.
Baseline, Week 17
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.
Baseline, Week 17
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.
Baseline, Week 17
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.
Baseline, Week 17
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.
Baseline, 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
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.
Baseline, Week 17
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.
Baseline through Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Regeneron Pharmaceuticals

Collaborators

Sanofi

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 7, 2018

Primary Completion (Actual)

May 14, 2019

Study Completion (Actual)

June 13, 2019

Study Registration Dates

First Submitted

June 5, 2018

First Submitted That Met QC Criteria

June 5, 2018

First Posted (Actual)

June 15, 2018

Study Record Updates

Last Update Posted (Actual)

May 28, 2020

Last Update Submitted That Met QC Criteria

May 11, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R668-ALG-16115

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Allergic Rhinitis

Clinical Trials on Placebo matching dupilumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Myanmar

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe