Clinical trial NCT02912468: A Controlled Clinical Study of Dupilumab in Patients With Bilateral Nasal Polyps
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Rhinosinusitis Phenotype With Nasal Polyps (CRSwNP)
Keywords: Nasal polyposis, Chronic rhinosinusitis, Intranasal corticosteroids, Dupilumab, Human monoclonal antibody
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2016-09-23
Enrollment: 276
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion criteria:

* Participants with bilateral sinonasal polyposis that despite prior treatment with systemic corticosteroids (SCS) anytime within the past 2 years; and/or had a medical contraindication / intolerance to SCS; and/or had prior surgery for NP at the screening visit, had:
* An endoscopic bilateral NPS of at least 5 out of a maximum score of 8 (with a minimum score of 2 in each nasal cavity).
* Ongoing symptoms (for at least 8 weeks prior to Visit \[V\] 1) of nasal congestion/blockage/obstruction with moderate or severe symptom severity (score 2 or 3) at V1 and a weekly average severity of greater than 1 at the time of randomization (V2), and another symptom such as loss of smell, rhinorrhea (anterior/posterior).
* Signed written informed consent.

Exclusion criteria:

* Participants \<18 years of age.
* Participants who were previously treated in dupilumab studies.
* Participants who had taken:
* Biologic therapy/systemic immunosuppressant to treat inflammatory disease or autoimmune disease (eg, rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis, etc.) within 2 months before V1 or 5 half-lives, whichever was longer.
* Any experimental monoclonal antibody (mAB) within 5 half-lives or within 6 months before V1 if the half-life was unknown.
* Anti-immunoglobulin E (IgE) therapy (omalizumab) within 130 days prior to V1.
* Participants who received leukotriene antagonists/modifiers at V1 unless they were on a continuous treatment for at least 30 days prior to V1.
* Initiated allergen immunotherapy within 3 months prior to V1 or planned to begin therapy or changed its dose during the run-in period or the randomized treatment period.
* Participants who undergone any intranasal and/or sinus surgery (including polypectomy) within 6 months prior to V1.
* Participants who had a sinonasal or sinus surgery changing the lateral wall structure of the nose making impossible the evaluation of NPS.
* Participants with conditions/concomitant diseases making them nonevaluable at V1 or for the primary efficacy endpoint such as:
* Antrochoanal polyps;
* Nasal septal deviation that would occlude at least one nostril;
* Acute sinusitis, nasal infection or upper respiratory infection;
* Ongoing rhinitis medicamentosa;
* Allergic granulomatous angiitis (Churg-Strauss syndrome), granulomatosis with polyangiitis (Wegener's granulomatosis), Young's syndrome, Kartagener's syndrome or other dyskinetic ciliary syndromes, concomitant cystic fibrosis;
* Radiologic suspicion, or confirmed invasive or expansive fungal rhinosinusitis.
* Participants with nasal cavity malignant tumor and benign tumors (eg, papilloma, blood boil, etc).
* Participants with forced expiratory volume in 1 second (FEV1) 50% or less (of predicted normal).
* Participants who received concomitant treatment prohibited in the study.
* Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit.
* History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening.
* Positive with hepatitis B surface antigen (HBsAg) or hepatitis C antibody at the screening visit.
* Active chronic or acute infection requiring systemic treatment within 2 weeks before the baseline visit.
* Known or suspected history of immunosuppression.
* Pregnant or breastfeeding women, or women planned to become pregnant or breastfeed during the study.
* Women unwilling to use adequate birth control, if of reproductive potential and sexually active.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Change From Baseline at Week 24 in Nasal Congestion/Obstruction Symptom Severity Score
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 24 in Nasal Polyp Score
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund-Mackay (LMK) Score
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 24 in Total Symptom Score (TSS)
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 24 in the University of Pennsylvania Smell Identification Test (UPSIT) Score
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 24 in Severity of Decreased/Loss of Smell as Assessed by Participant Daily
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 24 in 22-item Sino-nasal Outcome Test (SNOT-22) Scores
timeFrame: Baseline, Week 24
measure: Rescue Treatment Use: Estimate of Percentage of Participants With >=1 Event by Week 24 Obtained Using Kaplan-Meier Method
timeFrame: Baseline up to Week 24
measure: Change From Baseline at Week 24 in Visual Analogue Scale (VAS) for Rhinosinusitis
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 24 in Nasal Peak Inspiratory Flow (NPIF)
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 24 in Rhinorrhea Daily Symptom Score
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 24 in Forced Expiratory Volume in 1 Second (FEV1) for Participants With Asthma
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 24 in Asthma Control Questionnaire-6 (ACQ-6) Scores for Participants With Asthma
timeFrame: Baseline, Week 24
measure: 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)
timeFrame: 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)
measure: Change From Baseline at Weeks 36 and 48 in Nasal Polyp Score (Assessments Performed 12 and 24 Weeks After End of Treatment)
timeFrame: Baseline, Week 36, Week 48 (post-baseline assessments performed 12 and 24 weeks after end of treatment)
measure: Change From Baseline at Week 48 in Opacification of Sinuses Measured by Lund-Mackay Score (Assessment Performed 24 Weeks After End of Treatment)
timeFrame: Baseline, Week 48 (Post-baseline assessment performed 24 weeks after end of treatment)
measure: 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)
timeFrame: 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)
measure: Change From Baseline at Week 48 in University of Pennsylvania Smell Identification Test (Assessment Performed 24 Weeks After End of Treatment)
timeFrame: Baseline, Week 48 (Post-baseline assessment performed 24 weeks after end of treatment)
measure: 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)
timeFrame: 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)
measure: 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)
timeFrame: Baseline, Week 36 and Week 48 (Post-baseline assessments performed 12 and 24 weeks after end of treatment)
measure: Rescue Treatment Use: Estimate of Percentage of Participants With >=1 Event by Week 48 Obtained Using Kaplan-Meier Method
timeFrame: Baseline up to Week 48
measure: Change From Baseline at Weeks 36 and 48 in Visual Analog Scale for Rhinosinusitis (Assessments Performed 12 and 24 Weeks After End of Treatment)
timeFrame: Baseline, Week 36 and Week 48 (Post-baseline assessments performed 12 and 24 weeks after end of treatment)
measure: 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)
timeFrame: 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)
measure: 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)
timeFrame: Baseline, Week 48 (Post-baseline assessment performed 24 weeks after end of treatment)
measure: Change From Baseline at Week 48 in Asthma Control Questionnaire-6 Scores for Participants With Asthma (Assessment Performed 24 Weeks After End of Treatment)
timeFrame: Baseline, Week 48 (Post-baseline assessment performed 24 weeks after end of treatment)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs Leading to Treatment Discontinuation
timeFrame: Baseline up to 98 days following the last administration of study drug (up to 36 weeks)
measure: Functional Dupilumab Concentration in Serum
timeFrame: Baseline, Week 4, 8, 16, 24, 36, End of study (Week 48)
measure: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response
timeFrame: Baseline to End of study (Week 48)
measure: Mean Total Systemic Corticosteroids Rescue Dose Prescribed During Treatment Period
timeFrame: Baseline to Week 24
measure: Total Systemic Corticosteroids Rescue Intake Duration: Average Duration Per Participant
timeFrame: Baseline to Week 24
measure: Change From Baseline at Week 24 in European Quality of Life 5 Dimension (EQ-5D) Visual Analog Scale Score
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 24 in Nasal Congestion Symptom Severity Score: Subgroup of Participants With Asthma
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 24 in Nasal Congestion Symptom Severity Score: Subgroup of Participants With Prior Nasal Polyp Surgery
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 24 in Nasal Polyp Score: Subgroup of Participants With Asthma
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 24 in Nasal Polyp Score: Subgroup of Participants With Prior Nasal Polyp Surgery
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Asthma
timeFrame: Baseline, Week 24
measure: Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Prior Nasal Polyp Surgery
timeFrame: Baseline, Week 24
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Investigational Site Number 8400009
state: California
city: Orange
country: United States
facility: Investigational Site Number 8400004
state: California
city: San Diego
country: United States
facility: Investigational Site Number 8400014
state: California
city: Stockton
country: United States
facility: Investigational Site Number 8400002
state: California
city: Centennial
country: United States
facility: Investigational Site Number 8400016
state: Colorado
city: Tampa
country: United States
facility: Investigational Site Number 8400013
state: Florida
city: West Des Moines
country: United States
facility: Investigational Site Number 8400022
state: Iowa
city: Boston
country: United States
facility: Investigational Site Number 8400007
state: Massachusetts
city: Rochester
country: United States
facility: Investigational Site Number 8400005
state: Minnesota
city: Saint Louis
country: United States
facility: Investigational Site Number 8400021
state: Missouri
city: Winston-Salem
country: United States
facility: Investigational Site Number 8400008
state: North Carolina
city: Tulsa
country: United States
facility: Investigational Site Number 8400019
state: Oklahoma
city: Medford
country: United States
facility: Investigational Site Number 8400020
state: Oregon
city: Charleston
country: United States
facility: Investigational Site Number 8400018
state: South Carolina
city: Nashville
country: United States
facility: Investigational Site Number 8400003
state: Tennessee
city: Dallas
country: United States
facility: Investigational Site Number 8400001
state: Texas
city: Norfolk
country: United States
facility: Investigational Site Number 8400015
state: Virginia
city: Milwaukee
country: United States
facility: Investigational Site Number 8400010
state: Wisconsin
city: Plovdiv
country: Bulgaria
facility: Investigational Site Number 1000003
city: Sofia
country: Bulgaria
facility: Investigational Site Number 1000002
city: Sofia
country: Bulgaria
facility: Investigational Site Number 1000001
city: Hradec Kralove
country: Czechia
facility: Investigational Site Number 2030001
city: Pardubice
country: Czechia
facility: Investigational Site Number 2030002
city: Praha 2
country: Czechia
facility: Investigational Site Number 2030004
city: La Roche Sur Yon
country: France
facility: Investigational Site Number 2500005
city: Lille
country: France
facility: Investigational Site Number 2500007
city: Lyon
country: France
facility: Investigational Site Number 2500003
city: Montpellier
country: France
facility: Investigational Site Number 2500001
city: Nantes
country: France
facility: Investigational Site Number 2500006
city: Toulouse
country: France
facility: Investigational Site Number 2500002
city: Vandoeuvre-Les-Nancy
country: France
facility: Investigational Site Number 2500004
city: Berlin
country: Germany
facility: Investigational Site Number 2760001
city: München
country: Germany
facility: Investigational Site Number 2760003
city: Münster
country: Germany
facility: Investigational Site Number 2760002
city: Budapest
country: Hungary
facility: Investigational Site Number 3480006
city: Budapest
country: Hungary
facility: Investigational Site Number 3480007
city: Budapest
country: Hungary
facility: Investigational Site Number 3480004
city: Budapest
country: Hungary
facility: Investigational Site Number 3480003
city: Debrecen
country: Hungary
facility: Investigational Site Number 3480005
city: Pécs
country: Hungary
facility: Investigational Site Number 3480002
city: Szeged
country: Hungary
facility: Investigational Site Number 3480001
city: Bologna
country: Italy
facility: Investigational Site Number 3800007
city: Catania
country: Italy
facility: Investigational Site Number 3800002
city: Milano
country: Italy
facility: Investigational Site Number 3800004
city: Milano
country: Italy
facility: Investigational Site Number 3800006
city: Pisa
country: Italy
facility: Investigational Site Number 3800001
city: Rozzano
country: Italy
facility: Investigational Site Number 3800005
city: Varese
country: Italy
facility: Investigational Site Number 3800003
city: Amsterdam
country: Netherlands
facility: Investigational Site Number 5280001
city: Katowice
country: Poland
facility: Investigational Site Number 6160002
city: Lodz
country: Poland
facility: Investigational Site Number 6160001
city: Warszawa
country: Poland
facility: Investigational Site Number 6160003
city: Brasov
country: Romania
facility: Investigational Site Number 6420007
city: Brasov
country: Romania
facility: Investigational Site Number 6420013
city: Bucuresti
country: Romania
facility: Investigational Site Number 6420003
city: Cluj-Napoca
country: Romania
facility: Investigational Site Number 6420009
city: Craiova
country: Romania
facility: Investigational Site Number 6420008
city: Targu-Mures
country: Romania
facility: Investigational Site Number 6420010
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430004
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430003
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 6430001
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 6430007
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 6430002
city: Yaroslavl
country: Russian Federation
facility: Investigational Site Number 6430006
city: Ivano-Frankivsk
country: Ukraine
facility: Investigational Site Number 8040002
city: Kharkiv
country: Ukraine
facility: Investigational Site Number 8040004
city: Kyiv
country: Ukraine
facility: Investigational Site Number 8040005
city: Kyiv
country: Ukraine
facility: Investigational Site Number 8040006
city: Poltava
country: Ukraine
facility: Investigational Site Number 8040001
city: Ternopil
country: Ukraine
facility: Investigational Site Number 8040008
city: Bradford
country: United Kingdom
facility: Investigational Site Number 8260001
city: Dundee
country: United Kingdom
facility: Investigational Site Number 8260002
city: Great Yarmouth
country: United Kingdom
facility: Investigational Site Number 8260007
city: London
country: United Kingdom
facility: Investigational Site Number 8260006
city: Stockport
country: United Kingdom
facility: Investigational Site Number 8260004
city: Wigan
country: United Kingdom
facility: Investigational Site Number 8260005
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
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