Dupilumab As An Adjunct For Subcutaneous Grass Immunotherapy

Regeneron Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Allergic Rhinitis

Treatments: Drug: Placebo matching SCIT; Drug: Timothy Grass SCIT; Drug: Dupilumab; Drug: Placebo matching dupilumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03558997

R668-ALG-16115

Details and patient eligibility

About

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

Enrollment: 103 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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103 participants in 4 patient groups

Placebo

Experimental group

Description:

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.

Treatment:

Drug: Placebo matching dupilumab

Drug: Placebo matching SCIT

Dupilumab

Experimental group

Description:

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.

Treatment:

Drug: Dupilumab

Drug: Placebo matching SCIT

SCIT

Experimental group

Description:

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.

Treatment:

Drug: Placebo matching dupilumab

Drug: Timothy Grass SCIT

Dupilumab + SCIT

Experimental group

Description:

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.

Treatment:

Drug: Dupilumab

Drug: Timothy Grass SCIT