Dupilumab As An Adjunct For Subcutaneous Grass Immunotherapy
Condition: Allergic Rhinitis
MeSH terms: Rhinitis; Rhinitis, Allergic
Intervention: Dupilumab; Timothy Grass SCIT; Placebo matching dupilumab; Placebo matching SCIT
Intervention description: Dupilumab was administered SC in a single-use, pre-filled glass syringe; Timothy grass extract was administered SC.; Placebo matching dupilumab was prepared in the same formulation without the addition of protein; Placebo matching SCIT was prepared in the same formulation (SCIT diluent) without the addition of Timothy grass extract
Intervention MeSH terms: Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 103.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No

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