A Randomized, 24-Week Treatment, Double-blind, Placebo-controlled Efficacy and Safety Study of Dupilumab 300 mg Every Other Week, in Patients With Bilateral Nasal Polyposis on a Background Therapy With Intranasal Corticosteroids
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Chronic Rhinosinusitis Phenotype With Nasal Polyps (CRSwNP)
- Sponsor
- Sanofi
- Enrollment
- 276
- Locations
- 76
- Primary Endpoint
- Change From Baseline at Week 24 in Nasal Congestion/Obstruction Symptom Severity Score
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
Primary Objective:
To evaluate the efficacy of dupilumab 300 milligram (mg) every 2 weeks (q2w) compared to placebo on a background of mometasone furoate nasal spray (MFNS) in reducing nasal congestion/obstruction (NC) severity and endoscopic nasal polyp score (NPS) in participants with bilateral nasal polyposis (NP). In addition for Japan participants, reduction in computed tomography (CT) scan opacification of the sinuses was a coprimary objective.
Secondary Objectives:
- To evaluate the efficacy of dupilumab in improving total symptoms score (TSS).
- 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 Japan).
- To evaluate ability of dupilumab in reducing proportion of participants requiring treatment with systemic corticosteroids or NP surgery.
- To evaluate the effect of dupilumab on participant reported outcomes and health related quality of life outcome by sinonasal outcome test-22 (SNOT-22).
- To evaluate the effect of dupilumab in the subgroups of participants with prior surgery and co-morbid asthma (including non-steroid antiinflammatory drug [NSAID] exacerbated respiratory disease [ERD]).
- To evaluate residual effect in follow up.
- 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 expected to be up to 52 weeks that consisted of a 4-weeks run-in period, 24-weeks treatment period, and a 24-weeks post treatment period.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Placebo
Placebo (for dupilumab), 1 subcutaneous (SC) injection every 2 weeks (q2w) from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal mometasone furoate nasal spray (MFNS) at stable dose.
Intervention: Placebo
Placebo
Placebo (for dupilumab), 1 subcutaneous (SC) injection every 2 weeks (q2w) from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal mometasone furoate nasal spray (MFNS) at stable dose.
Intervention: Mometasone furoate 50 micrograms
Dupilumab 300 mg
Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Intervention: Dupilumab SAR231893 (REGN668)
Dupilumab 300 mg
Dupilumab 300 mg SC injection q2w from Day 1 of Week 0 up to Week 24 added to background therapy of intranasal MFNS at stable dose.
Intervention: Mometasone furoate 50 micrograms
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.
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.
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)
- Rescue Treatment Use: Estimate of Percentage of Participants With >=1 Event by Week 24 Obtained Using Kaplan-Meier Method(Baseline up to Week 24)
- Change From Baseline at Week 24 in Visual Analogue Scale (VAS) for Rhinosinusitis(Baseline, Week 24)
- 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 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) Scores for Participants With Asthma(Baseline, Week 24)
- Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Nasal Congestion Symptom Severity Score (Assessments Performed 4-24 Weeks After End of Treatment)(Baseline, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 (Post-baseline assessments performed 4-24 weeks after end of treatment))
- Change From Baseline at Weeks 36 and 48 in Nasal Polyp Score (Assessments Performed 12 and 24 Weeks After End of Treatment)(Baseline, Week 36, Week 48 (post-baseline assessments performed 12 and 24 weeks after end of treatment))
- Change From Baseline at Week 48 in Opacification of Sinuses Measured by Lund-Mackay Score (Assessment Performed 24 Weeks After End of Treatment)(Baseline, Week 48 (Post-baseline assessment performed 24 weeks after end of treatment))
- Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Total Symptom Score (Assessments Performed 4-24 Weeks After End of Treatment)(Baseline, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 (Post-baseline assessments performed 4-24 weeks after end of treatment))
- Change From Baseline at Week 48 in University of Pennsylvania Smell Identification Test (Assessment Performed 24 Weeks After End of Treatment)(Baseline, Week 48 (Post-baseline assessment performed 24 weeks after end of treatment))
- Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Severity of Decreased/Loss of Smell as Assessed by Participant Daily (Assessments Performed 4-24 Weeks After End of Treatment)(Baseline, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 (Post-baseline assessments performed 4-24 weeks after end of treatment))
- Change From Baseline at Weeks 36 and 48 in 22-item Sino-nasal Outcome Test Scores (Assessments Performed 12 and 24 Weeks After End of Treatment)(Baseline, Week 36 and Week 48 (Post-baseline assessments performed 12 and 24 weeks after end of treatment))
- Rescue Treatment Use: Estimate of Percentage of Participants With >=1 Event by Week 48 Obtained Using Kaplan-Meier Method(Baseline up to Week 48)
- Change From Baseline at Weeks 36 and 48 in Visual Analog Scale for Rhinosinusitis (Assessments Performed 12 and 24 Weeks After End of Treatment)(Baseline, Week 36 and Week 48 (Post-baseline assessments performed 12 and 24 weeks after end of treatment))
- Change From Baseline at Weeks 28, 32, 36, 40, 44 and 48 in Rhinorrhea Daily Symptom Score (Assessments Performed 4-24 Weeks After End of Treatment)(Baseline, Week 28, Week 32, Week 36, Week 40, Week 44 and Week 48 (Post-baseline assessments performed 4-24 weeks after end of treatment))
- Change From Baseline at Week 48 in Forced Expiratory Volume in 1 Second for Participants With Asthma (Assessment Performed 24 Weeks After End of Treatment)(Baseline, Week 48 (Post-baseline assessment performed 24 weeks after end of treatment))
- Change From Baseline at Week 48 in Asthma Control Questionnaire-6 Scores for Participants With Asthma (Assessment Performed 24 Weeks After End of Treatment)(Baseline, Week 48 (Post-baseline assessment performed 24 weeks after end of treatment))
- Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs Leading to Treatment Discontinuation(Baseline up to 98 days following the last administration of study drug (up to 36 weeks))
- Functional Dupilumab Concentration in Serum(Baseline, Week 4, 8, 16, 24, 36, End of study (Week 48))
- Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response(Baseline to End of study (Week 48))
- Mean Total Systemic Corticosteroids Rescue Dose Prescribed During Treatment Period(Baseline to Week 24)
- Total Systemic Corticosteroids Rescue Intake Duration: Average Duration Per Participant(Baseline to Week 24)
- Change From Baseline at Week 24 in European Quality of Life 5 Dimension (EQ-5D) Visual Analog Scale Score(Baseline, Week 24)
- Change From Baseline at Week 24 in Nasal Congestion Symptom Severity Score: Subgroup of Participants With Asthma(Baseline, Week 24)
- Change From Baseline at Week 24 in Nasal Congestion Symptom Severity Score: Subgroup of Participants With Prior Nasal Polyp Surgery(Baseline, Week 24)
- Change From Baseline at Week 24 in Nasal Polyp Score: Subgroup of Participants With Asthma(Baseline, Week 24)
- 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 24 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Asthma(Baseline, Week 24)
- 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)