Clinical trial NCT03558997: Dupilumab As An Adjunct For Subcutaneous Grass Immunotherapy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Allergic Rhinitis
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2018-06-15
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility 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

Primary outcomes:
measure: 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
timeFrame: Baseline, Week 17
Secondary outcomes:
measure: 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
timeFrame: Baseline, Week 17
measure: 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
timeFrame: Baseline, Week 17
measure: 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
timeFrame: Baseline, Week 17
measure: 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
timeFrame: Baseline, Week 17
measure: 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
timeFrame: Baseline, Week 17
measure: Change From Baseline in Serum Timothy Grass Specific Immunoglobulin G4 (sIgG4) to Week 17
timeFrame: Baseline, Week 17
measure: Percent Change From Baseline in Serum Timothy Grass Specific Immunoglobulin G4 (sIgG4) to Week 17
timeFrame: Baseline, Week 17
measure: Change From Baseline in Serum Timothy Grass Specific Immunoglobulin E (sIgE) to Week 17
timeFrame: Baseline, Week 17
measure: Percent Change From Baseline in Serum Timothy Grass Specific Immunoglobulin E (sIgE) to Week 17
timeFrame: Baseline, Week 17
measure: 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
timeFrame: Baseline, Week 17
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: Baseline through Week 24
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Regeneron Investigational Site
state: California
city: Mountain View
country: United States
facility: Regeneron Investigational Site
state: California
city: Walnut Creek
country: United States
facility: Regeneron Investigational Site
state: California
city: Baltimore
country: United States
facility: Regeneron Investigational Site
state: Maryland
city: Andover
country: United States
facility: Regeneron Investigational Site
state: Massachusetts
city: North Dartmouth
country: United States
facility: Regeneron Investigational Site
state: Massachusetts
city: Saint Louis
country: United States
facility: Regeneron Investigational Site
state: Missouri
city: Bellevue
country: United States
facility: Regeneron Investigational Site
state: Nebraska
city: Portland
country: United States
facility: Regeneron Investigational Site
state: Oregon
city: East Providence
country: United States
facility: Regeneron Investigational Site
state: Rhode Island
city: Seattle
country: United States
facility: Regeneron Investigational Site
state: Washington
city: Madison
country: United States
facility: Regeneron Investigational Site
state: Wisconsin
city: Kingston
country: Canada
facility: Regeneron Investigational Site
state: Ontario
city: Mississauga
country: Canada
facility: Regeneron Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: Regeneron Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: Regeneron Investigational Site
state: Ontario
city: Québec
country: Canada
facility: Regeneron Investigational Site
state: Quebec
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: Kamal MA, Franchetti Y, Lai CH, Xu C, Wang CQ, Radin AR, O'Brien MP, Ruddy M, Davis JD. Pharmacokinetics and Concentration-Response of Dupilumab in Patients With Seasonal Allergic Rhinitis. J Clin Pharmacol. 2022 May;62(5):689-695. doi: 10.1002/jcph.2004. Epub 2022 Jan 6.
citation: Corren J, Saini SS, Gagnon R, Moss MH, Sussman G, Jacobs J, Laws E, Chung ES, Constant T, Sun Y, Maloney J, Hamilton JD, Ruddy M, Wang CQ, O'Brien MP. Short-Term Subcutaneous Allergy Immunotherapy and Dupilumab are Well Tolerated in Allergic Rhinitis: A Randomized Trial. J Asthma Allergy. 2021 Aug 16;14:1045-1063. doi: 10.2147/JAA.S318892. eCollection 2021.