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Trial record 1 of 1 for:    NCT03558997
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Dupilumab As An Adjunct For Subcutaneous Grass Immunotherapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03558997
Recruitment Status : Completed
First Posted : June 15, 2018
Results First Posted : May 28, 2020
Last Update Posted : May 28, 2020
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

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

Condition or disease Intervention/treatment Phase
Allergic Rhinitis Drug: Dupilumab Drug: Timothy Grass SCIT Drug: Placebo matching dupilumab Drug: Placebo matching SCIT Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 103 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : June 7, 2018
Actual Primary Completion Date : May 14, 2019
Actual Study Completion Date : June 13, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Dupilumab

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: Dupilumab
Dupilumab was administered SC in a single-use, pre-filled glass syringe
Other Names:
  • DUPIXENT®
  • REGN668
  • SAR231893

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

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: Timothy Grass SCIT
Timothy grass extract was administered SC.

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

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:
  • DUPIXENT®
  • REGN668
  • SAR231893

Drug: Timothy Grass SCIT
Timothy grass extract was administered SC.




Primary Outcome Measures :
  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 Outcome Measures :
  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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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/ exclusion criteria apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03558997


Locations
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United States, California
Regeneron Investigational Site
Los Angeles, California, United States, 90025
Regeneron Investigational Site
Mountain View, California, United States, 94040
Regeneron Investigational Site
Walnut Creek, California, United States, 94598
United States, Maryland
Regeneron Investigational Site
Baltimore, Maryland, United States, 21224
United States, Massachusetts
Regeneron Investigational Site
Andover, Massachusetts, United States, 01810
Regeneron Investigational Site
North Dartmouth, Massachusetts, United States, 02747
United States, Missouri
Regeneron Investigational Site
Saint Louis, Missouri, United States, 63141
United States, Nebraska
Regeneron Investigational Site
Bellevue, Nebraska, United States, 68123
United States, Oregon
Regeneron Investigational Site
Portland, Oregon, United States, 97202
United States, Rhode Island
Regeneron Investigational Site
East Providence, Rhode Island, United States, 02914
United States, Washington
Regeneron Investigational Site
Seattle, Washington, United States, 98115
United States, Wisconsin
Regeneron Investigational Site
Madison, Wisconsin, United States, 53792-9988
Canada, Ontario
Regeneron Investigational Site
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
Canada, Quebec
Regeneron Investigational Site
Québec, Quebec, Canada, G1V 4W2
Sponsors and Collaborators
Regeneron Pharmaceuticals
Sanofi
Investigators
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Study Director: Clinical Trial Management Regeneron Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Regeneron Pharmaceuticals:
Study Protocol  [PDF] November 13, 2018
Statistical Analysis Plan  [PDF] June 24, 2019

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Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03558997    
Other Study ID Numbers: R668-ALG-16115
First Posted: June 15, 2018    Key Record Dates
Results First Posted: May 28, 2020
Last Update Posted: May 28, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Rhinitis
Rhinitis, Allergic
Nose Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs