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

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

103

participants targeted

Target at P50-P75 for phase_2

Timeline

Completed

Started Jun 2018

Shorter than P25 for phase_2

Geographic Reach

2 countries

17 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

1 year study duration

First Submitted

Initial submission to the registry

June 5, 2018

Completed

2 days until next milestone

Study Start

First participant enrolled

June 7, 2018

Completed

8 days until next milestone

First Posted

Study publicly available on registry

June 15, 2018

Completed

11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 14, 2019

Completed

1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

June 13, 2019

Completed

12 months until next milestone

Results Posted

Study results publicly available

May 28, 2020

Completed

Last Updated

May 28, 2020

Status Verified

May 1, 2020

Enrollment Period

11 months

First QC Date

June 5, 2018

Results QC Date

May 11, 2020

Last Update Submit

May 11, 2020

Conditions

Allergic Rhinitis

Outcome Measures

Primary Outcomes (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
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.
Baseline, Week 17

Secondary Outcomes (11)

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
Baseline, Week 17
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
Baseline, Week 17
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
Baseline, Week 17
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
Baseline, Week 17
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
Baseline, Week 17
+6 more secondary outcomes

Study Arms (4)

Placebo

EXPERIMENTAL

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 dupilumabDrug: Placebo matching SCIT

Dupilumab

EXPERIMENTAL

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: DupilumabDrug: Placebo matching SCIT

SCIT

EXPERIMENTAL

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 SCITDrug: Placebo matching dupilumab

Dupilumab + SCIT

EXPERIMENTAL

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: DupilumabDrug: Timothy Grass SCIT

Interventions

DupilumabDRUG

Dupilumab was administered SC in a single-use, pre-filled glass syringe

Also known as: DUPIXENT®, REGN668, SAR231893

DupilumabDupilumab + SCIT

Timothy Grass SCITDRUG

Timothy grass extract was administered SC.

Dupilumab + SCITSCIT

Placebo matching dupilumabDRUG

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

PlaceboSCIT

Placebo matching SCITDRUG

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

DupilumabPlacebo

Eligibility Criteria

Age18 Years - 55 Years

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64)

You may qualify if:

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)

You may not qualify if:

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

Contact the study team to confirm eligibility.