Phase 2
N=103
Dupilumab As An Adjunct For Subcutaneous Grass Immunotherapy
Allergic Rhinitis
Bottom Line
View on ClinicalTrials.gov: NCT03558997 ↗Enrolled (actual)
103
Serious AEs
4.9%
Results posted
May 2020
Primary outcome: 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 — -56.76; -52.03 Percent Change — p=0.7185
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Dupilumab (Drug); Timothy Grass SCIT (Drug); Placebo matching dupilumab (Drug); Placebo matching SCIT (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Regeneron Pharmaceuticals
- Primary completion
- May 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| 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 |
-56.76; -52.03 | 0.7185 |
| 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 |
-3.07; -2.77 | 0.5438 |
| 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 |
-1.85; -1.83 | 0.9559 |
| 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 |
-28.82; -21.57 | 0.5416 |
| 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 |
-1.83; -2.77 | 0.0414 sig |
| 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 |
-21.57; -52.03 | 0.0108 sig |
| SECONDARY Change From Baseline in Serum Timothy Grass Specific Immunoglobulin G4 (sIgG4) to Week 17 |
1.705; 3.550 | 0.1449 |
| SECONDARY Percent Change From Baseline in Serum Timothy Grass Specific Immunoglobulin G4 (sIgG4) to Week 17 |
1444.49; 1896.25 | 0.1231 |
| SECONDARY Change From Baseline in Serum Timothy Grass Specific Immunoglobulin E (sIgE) to Week 17 |
6.460; -2.990 | <0.0001 sig |
| SECONDARY Percent Change From Baseline in Serum Timothy Grass Specific Immunoglobulin E (sIgE) to Week 17 |
81.27; -56.44 | <0.0001 sig |
| 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 |
0.745; 1.720 | <0.0001 sig |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs |
21; 18; 24; 22; 1; 1 | — |
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
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT03558997). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.