A Randomized, Double-blind, 52-week, Placebo Controlled Efficacy and Safety Study of Dupilumab, in Patients With Bilateral Nasal Polyposis on a Background Therapy With Intranasal Corticosteroids
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Sanofi
- Enrollment
- 448
- Locations
- 123
- Primary Endpoint
- Change From Baseline at Week 24 in Nasal Congestion/Obstruction Symptom Severity Score
Study Overview
Brief Summary
Primary Objective:
To evaluate the efficacy of dupilumab 300 mg every 2 weeks (q2w) compared to placebo on a background of mometasone furoate nasal spray (MFNS) in reducing nasal congestion (NC)/obstruction severity and endoscopic nasal polyp score (NPS) in participants with bilateral nasal polyps (NP). In addition for Japanese participants, reduction in computed tomography (CT) scan opacification of the sinuses was a co-primary objective.
Secondary Objectives:
- To evaluate the efficacy of dupilumab in improving total symptoms score.
- To evaluate the efficacy of dupilumab in improving sense of smell.
- To evaluate the efficacy of dupilumab in reducing CT scan opacification of the sinuses (primary objective for Japanese participants).
- To evaluate ability of dupilumab in reducing proportion of participants who required treatment with systemic corticosteroids (SCS) or surgery for NP.
- To evaluate the effect of dupilumab on participant reported outcomes and health related quality of life.
- To evaluate the efficacy of dupilumab 300 mg q2w up to Week 52.
- To evaluate the efficacy of dupilumab 300 mg q2w up to Week 24 followed by 300 mg every 4 weeks (q4w) up to Week 52.
- To evaluate the effect of dupilumab in the subgroups of participants with prior surgery and comorbid asthma including non-steroid anti-inflammatory drug exacerbated respiratory disease.
- To evaluate the safety of dupilumab in participants with bilateral NP.
- To evaluate functional dupilumab concentrations (systemic exposure) and incidence of treatment emergent anti-drug antibodies.
Detailed Description
The total study duration per participant was up to 68 weeks that consisted of a 4-weeks run-in period, 52-weeks treatment period, and a 12-weeks post treatment period.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Dupilumab 300 mg q2w
Dupilumab 300 mg subcutaneous (SC) injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Intervention: Dupilumab SAR231893 (REGN668) (Drug)
Dupilumab 300 mg q2w
Dupilumab 300 mg subcutaneous (SC) injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Intervention: Mometasone furoate nasal spray (Drug)
Dupilumab 300 mg q2w then q4w
Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 and then 300 mg q4w until Week 52 added to background therapy of intranasal MFNS at stable dose. After Week 24, Dupilumab administration was alternated with matched placebo injection every other week up to Week 50.
Intervention: Dupilumab SAR231893 (REGN668) (Drug)
Dupilumab 300 mg q2w then q4w
Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 and then 300 mg q4w until Week 52 added to background therapy of intranasal MFNS at stable dose. After Week 24, Dupilumab administration was alternated with matched placebo injection every other week up to Week 50.
Intervention: Placebo (Drug)
Dupilumab 300 mg q2w then q4w
Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 and then 300 mg q4w until Week 52 added to background therapy of intranasal MFNS at stable dose. After Week 24, Dupilumab administration was alternated with matched placebo injection every other week up to Week 50.
Intervention: Mometasone furoate nasal spray (Drug)
Placebo
Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Intervention: Placebo (Drug)
Placebo
Placebo (for dupilumab), 1 SC injection q2w from Day 1 of Week 0 up to Week 52 added to background therapy of intranasal MFNS at stable dose.
Intervention: Mometasone furoate nasal spray (Drug)
Outcomes
Primary Outcomes
Change From Baseline at Week 24 in Nasal Congestion/Obstruction Symptom Severity Score
Time Frame: Baseline, Week 24
NC symptom severity was assessed by the participants on a daily basis from visit 1 and throughout the study using an e-diary on a scale of 0 to 3, where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms, with higher scores indicated more severity. Least squares (LS) means and standard error (SE) were obtained from Analysis of covariance (ANCOVA) model described in Statistical Analysis Overview. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments.
Change From Baseline at Week 24 in Nasal Polyp Score
Time Frame: Baseline, Week 24
NPS: sum of right, left nostril scores, evaluated by nasal endoscopy. For each nostril, NPS was graded based on polyp size from 0 = no polyps to 4 = large polyps causing complete obstruction of inferior nasal cavity; lower score = smaller sized polyps. Total NPS: sum of right and left nostril scores, ranges from 0 (no polyps) to 8 (large polyps), higher score = more severe disease. NPS was assessed by centralized, blinded, independent review of the nasal endoscopy video recordings. LS means and SE were obtained from ANCOVA model described in Statistical Analysis Overview. All participants randomized to receive Dupilumab had been on 300 mg q2w regimen until Week 24 and analyzed as a pooled population for Week 24 assessments.
Secondary Outcomes
- Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund Mackay (LMK) Score(Baseline, Week 24)
- Change From Baseline at Week 24 in Total Symptom Score (TSS)(Baseline, Week 24)
- Change From Baseline at Week 24 in the University of Pennsylvania Smell Identification Test (UPSIT) Score(Baseline, Week 24)
- Change From Baseline at Week 24 in Severity of Decreased/Loss of Smell as Assessed by Participant Daily(Baseline, Week 24)
- Change From Baseline at Week 24 in 22-item Sino-nasal Outcome Test (SNOT-22) Scores(Baseline, Week 24)
- Change From Baseline at Week 52 in Nasal Polyp Score(Baseline, Week 52)
- Change From Baseline at Week 52 in Nasal Congestion/Obstruction Symptom Severity Score(Baseline, Week 52)
- Change From Baseline at Week 52 in 22-item Sino-nasal Outcome Test Scores(Baseline, Week 52)
- Rescue Treatment Use: Estimate of Percentage of Participants With Greater Than or Equal to (>=) 1 Event by Week 52 Obtained Using Kaplan-Meier Method(Baseline up to 52 weeks)
- Change From Baseline at Week 52 in Total Symptom Score(Baseline, Week 52)
- Change From Baseline at Week 52 in the University of Pennsylvania Smell Identification Test Score(Baseline, Week 52)
- Change From Baseline at Week 52 in Severity of Decreased/Loss of Smell(Baseline, Week 52)
- Change From Baseline at Week 52 in Opacification of Sinuses Measured by Lund-Mackay Score(Baseline, Week 52)
- Change From Baseline at Week 52 in Forced Expiratory Volume in 1 Second for Participants With Asthma(Baseline, Week 52)
- Change From Baseline at Week 24 in Visual Analogue Scale (VAS) for Rhinosinusitis(Baseline, Week 24)
- Change From Baseline at Week 52 in Visual Analogue Scale for Rhinosinusitis(Baseline, Week 52)
- Change From Baseline at Week 24 in Nasal Peak Inspiratory Flow (NPIF)(Baseline, Week 24)
- Change From Baseline at Week 24 in Rhinorrhea Daily Symptom Score(Baseline, Week 24)
- Change From Baseline at Week 52 in Rhinorrhea Daily Symptom Score(Baseline, Week 52)
- Mean Total Systemic Corticosteroids Rescue Dose Prescribed During Treatment Period(Baseline to Week 52)
- Total Systemic Corticosteroids Rescue Intake Duration: Average Duration Per Participant(Baseline to Week 52)
- Changed From Baseline at Week 24 in Forced Expiratory Volume in 1 Second (FEV1) for Participants With Asthma(Baseline, Week 24)
- Change From Baseline at Week 24 in Asthma Control Questionnaire-6 (ACQ-6) for Participants With Asthma(Baseline, Week 24)
- Change From Baseline at Week 52 in Asthma Control Questionnaire-6 for Participants With Asthma(Baseline, Week 52)
- Change From Baseline at Week 24 in Nasal Congestion/Obstruction Symptom Severity Score: Subgroup of Participants With Asthma(Baseline, Week 24)
- Change From Baseline at Week 52 in Nasal Congestion/Obstruction Symptom Severity Score: Subgroup of Participants With Asthma(Baseline, Week 52)
- Change From Baseline at Week 24 in Nasal Congestion/Obstruction Symptom Severity Score: Subgroup of Participants With Prior Nasal Polyp Surgery(Baseline, Week 24)
- Change From Baseline at Week 52 in Nasal Congestion/Obstruction Symptom Severity Score: Subgroup of Participants With Prior Nasal Polyp Surgery(Baseline, Week 52)
- Change From Baseline at Week 24 in Nasal Polyp Score: Subgroup of Participants With Asthma(Baseline, Week 24)
- Change From Baseline at Week 52 in Nasal Polyp Score: Subgroup of Participants With Asthma(Baseline, Week 52)
- Change From Baseline at Week 24 in Nasal Polyp Score: Subgroup of Participants With Prior Nasal Polyp Surgery(Baseline, Week 24)
- Change From Baseline at Week 52 in Nasal Polyp Score: Subgroup of Participants With Prior Nasal Polyp Surgery(Baseline, Week 52)
- Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Asthma(Baseline, Week 24)
- Change From Baseline at Week 52 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Asthma(Baseline, Week 52)
- Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Prior Nasal Polyp Surgery(Baseline, Week 24)
- Change From Baseline at Week 52 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Prior Nasal Polyp Surgery(Baseline, Week 52)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs Leading to Treatment Discontinuation(Baseline up to 84 days after last dose of study drug (up to 64 weeks))
- Change From Baseline at Week 24 in European Quality of Life 5 Dimension Scale (EQ-5D) Visual Analog Scale Score(Baseline, Week 24)
- Change From Baseline at Week 52 in European Quality of Life 5 Dimension Scale Visual Analog Scale Score(Baseline, Week 52)
- Functional Dupilumab Concentration in Serum(Baseline, Week 2, Week 4, Week 16, Week 24, Week 40, End of treatment (Week 52), End of study (Week 64))
- Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies Response (ADA)(Baseline to Week 52)