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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02898454




Registration number
NCT02898454
Ethics application status
Date submitted
8/09/2016
Date registered
13/09/2016

Titles & IDs
Public title
Controlled Clinical Study of Dupilumab in Patients With Nasal Polyps
Scientific title
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
Secondary ID [1] 0 0
2015-001314-10
Secondary ID [2] 0 0
EFC14280
Universal Trial Number (UTN)
Trial acronym
SINUS-52
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Rhinosinusitis Phenotype With Nasal Polyps (CRSwNP) 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Dupilumab SAR231893 (REGN668)
Treatment: Drugs - Placebo
Treatment: Drugs - Mometasone furoate nasal spray

Experimental: 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.

Experimental: 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.

Placebo comparator: 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.


Treatment: Drugs: Dupilumab SAR231893 (REGN668)
Pharmaceutical form: Solution

Route of administration: Subcutaneous

Treatment: Drugs: Placebo
Pharmaceutical form: Solution

Route of administration: Subcutaneous

Treatment: Drugs: Mometasone furoate nasal spray
Pharmaceutical form: Suspension

Route of administration: Intranasal
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline at Week 24 in Nasal Congestion/Obstruction Symptom Severity Score
Timepoint [1] 0 0
Baseline, Week 24
Primary outcome [2] 0 0
Change From Baseline at Week 24 in Nasal Polyp Score
Timepoint [2] 0 0
Baseline, Week 24
Secondary outcome [1] 0 0
Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund Mackay (LMK) Score
Timepoint [1] 0 0
Baseline, Week 24
Secondary outcome [2] 0 0
Change From Baseline at Week 24 in Total Symptom Score (TSS)
Timepoint [2] 0 0
Baseline, Week 24
Secondary outcome [3] 0 0
Change From Baseline at Week 24 in the University of Pennsylvania Smell Identification Test (UPSIT) Score
Timepoint [3] 0 0
Baseline, Week 24
Secondary outcome [4] 0 0
Change From Baseline at Week 24 in Severity of Decreased/Loss of Smell as Assessed by Participant Daily
Timepoint [4] 0 0
Baseline, Week 24
Secondary outcome [5] 0 0
Change From Baseline at Week 24 in 22-item Sino-nasal Outcome Test (SNOT-22) Scores
Timepoint [5] 0 0
Baseline, Week 24
Secondary outcome [6] 0 0
Change From Baseline at Week 52 in Nasal Polyp Score
Timepoint [6] 0 0
Baseline, Week 52
Secondary outcome [7] 0 0
Change From Baseline at Week 52 in Nasal Congestion/Obstruction Symptom Severity Score
Timepoint [7] 0 0
Baseline, Week 52
Secondary outcome [8] 0 0
Change From Baseline at Week 52 in 22-item Sino-nasal Outcome Test Scores
Timepoint [8] 0 0
Baseline, Week 52
Secondary outcome [9] 0 0
Rescue Treatment Use: Estimate of Percentage of Participants With Greater Than or Equal to (>=) 1 Event by Week 52 Obtained Using Kaplan-Meier Method
Timepoint [9] 0 0
Baseline up to 52 weeks
Secondary outcome [10] 0 0
Change From Baseline at Week 52 in Total Symptom Score
Timepoint [10] 0 0
Baseline, Week 52
Secondary outcome [11] 0 0
Change From Baseline at Week 52 in the University of Pennsylvania Smell Identification Test Score
Timepoint [11] 0 0
Baseline, Week 52
Secondary outcome [12] 0 0
Change From Baseline at Week 52 in Severity of Decreased/Loss of Smell
Timepoint [12] 0 0
Baseline, Week 52
Secondary outcome [13] 0 0
Change From Baseline at Week 52 in Opacification of Sinuses Measured by Lund-Mackay Score
Timepoint [13] 0 0
Baseline, Week 52
Secondary outcome [14] 0 0
Change From Baseline at Week 24 in Visual Analogue Scale (VAS) for Rhinosinusitis
Timepoint [14] 0 0
Baseline, Week 24
Secondary outcome [15] 0 0
Change From Baseline at Week 52 in Visual Analogue Scale for Rhinosinusitis
Timepoint [15] 0 0
Baseline, Week 52
Secondary outcome [16] 0 0
Change From Baseline at Week 24 in Nasal Peak Inspiratory Flow (NPIF)
Timepoint [16] 0 0
Baseline, Week 24
Secondary outcome [17] 0 0
Change From Baseline at Week 24 in Rhinorrhea Daily Symptom Score
Timepoint [17] 0 0
Baseline, Week 24
Secondary outcome [18] 0 0
Change From Baseline at Week 52 in Rhinorrhea Daily Symptom Score
Timepoint [18] 0 0
Baseline, Week 52
Secondary outcome [19] 0 0
Mean Total Systemic Corticosteroids Rescue Dose Prescribed During Treatment Period
Timepoint [19] 0 0
Baseline to Week 52
Secondary outcome [20] 0 0
Total Systemic Corticosteroids Rescue Intake Duration: Average Duration Per Participant
Timepoint [20] 0 0
Baseline to Week 52
Secondary outcome [21] 0 0
Changed From Baseline at Week 24 in Forced Expiratory Volume in 1 Second (FEV1) for Participants With Asthma
Timepoint [21] 0 0
Baseline, Week 24
Secondary outcome [22] 0 0
Change From Baseline at Week 52 in Forced Expiratory Volume in 1 Second for Participants With Asthma
Timepoint [22] 0 0
Baseline, Week 52
Secondary outcome [23] 0 0
Change From Baseline at Week 24 in Asthma Control Questionnaire-6 (ACQ-6) for Participants With Asthma
Timepoint [23] 0 0
Baseline, Week 24
Secondary outcome [24] 0 0
Change From Baseline at Week 52 in Asthma Control Questionnaire-6 for Participants With Asthma
Timepoint [24] 0 0
Baseline, Week 52
Secondary outcome [25] 0 0
Change From Baseline at Week 24 in Nasal Congestion/Obstruction Symptom Severity Score: Subgroup of Participants With Asthma
Timepoint [25] 0 0
Baseline, Week 24
Secondary outcome [26] 0 0
Change From Baseline at Week 52 in Nasal Congestion/Obstruction Symptom Severity Score: Subgroup of Participants With Asthma
Timepoint [26] 0 0
Baseline, Week 52
Secondary outcome [27] 0 0
Change From Baseline at Week 24 in Nasal Congestion/Obstruction Symptom Severity Score: Subgroup of Participants With Prior Nasal Polyp Surgery
Timepoint [27] 0 0
Baseline, Week 24
Secondary outcome [28] 0 0
Change From Baseline at Week 52 in Nasal Congestion/Obstruction Symptom Severity Score: Subgroup of Participants With Prior Nasal Polyp Surgery
Timepoint [28] 0 0
Baseline, Week 52
Secondary outcome [29] 0 0
Change From Baseline at Week 24 in Nasal Polyp Score: Subgroup of Participants With Asthma
Timepoint [29] 0 0
Baseline, Week 24
Secondary outcome [30] 0 0
Change From Baseline at Week 52 in Nasal Polyp Score: Subgroup of Participants With Asthma
Timepoint [30] 0 0
Baseline, Week 52
Secondary outcome [31] 0 0
Change From Baseline at Week 24 in Nasal Polyp Score: Subgroup of Participants With Prior Nasal Polyp Surgery
Timepoint [31] 0 0
Baseline, Week 24
Secondary outcome [32] 0 0
Change From Baseline at Week 52 in Nasal Polyp Score: Subgroup of Participants With Prior Nasal Polyp Surgery
Timepoint [32] 0 0
Baseline, Week 52
Secondary outcome [33] 0 0
Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Asthma
Timepoint [33] 0 0
Baseline, Week 24
Secondary outcome [34] 0 0
Change From Baseline at Week 52 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Asthma
Timepoint [34] 0 0
Baseline, Week 52
Secondary outcome [35] 0 0
Change From Baseline at Week 24 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Prior Nasal Polyp Surgery
Timepoint [35] 0 0
Baseline, Week 24
Secondary outcome [36] 0 0
Change From Baseline at Week 52 in Opacification of Sinuses Measured by Lund Mackay Score: Subgroup of Participants With Prior Nasal Polyp Surgery
Timepoint [36] 0 0
Baseline, Week 52
Secondary outcome [37] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs Leading to Treatment Discontinuation
Timepoint [37] 0 0
Baseline up to 84 days after last dose of study drug (up to 64 weeks)
Secondary outcome [38] 0 0
Change From Baseline at Week 24 in European Quality of Life 5 Dimension Scale (EQ-5D) Visual Analog Scale Score
Timepoint [38] 0 0
Baseline, Week 24
Secondary outcome [39] 0 0
Change From Baseline at Week 52 in European Quality of Life 5 Dimension Scale Visual Analog Scale Score
Timepoint [39] 0 0
Baseline, Week 52
Secondary outcome [40] 0 0
Functional Dupilumab Concentration in Serum
Timepoint [40] 0 0
Baseline, Week 2, Week 4, Week 16, Week 24, Week 40, End of treatment (Week 52), End of study (Week 64)
Secondary outcome [41] 0 0
Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies Response (ADA)
Timepoint [41] 0 0
Baseline to Week 52

Eligibility
Key inclusion criteria
Inclusion criteria :

* Participants with bilateral sino-nasal polyposis that despite prior treatment with 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 at Visit 1 (V1) 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 before V1) of NC/blockage/obstruction with moderate or severe symptom severity (score 2 or 3) at V1 and a weekly average severity of greater than 1 at time of randomization (V2), and another symptom such as loss of smell, rhinorrhea (anterior/posterior).
* Signed written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

* Participants <18 years of age.
* Participant who had been previously treated in dupilumab studies.
* Participant 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 within 5 half-lives or within 6 months before V1 if the half-life was unknown.
* Anti-immunoglobulin E 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.
* Initiation of allergen immunotherapy within 3 months prior to V1 or a plan to begin therapy or change its dose during the run-in period or the randomized treatment period.
* Participants who underwent any and/or sinus surgery (including polypectomy) within 6 months before V1.
* Participants who had a sino-nasal or sinus surgery changing the lateral wall structure of the nose making impossible the evaluation of NPS.
* Participants with conditions/concomitant diseases making them non evaluable 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 50% or less (of predicted normal).
* Participants who received concomitant treatment prohibited in the study.
* Treatment with a live (attenuated) vaccine within 4 weeks before the baseline visit.
* 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 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 planning 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/11/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
16/11/2018
Sample size
Target
Accrual to date
Final
448
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Investigational Site Number 0360002 - Clayton
Recruitment hospital [2] 0 0
Investigational Site Number 0360004 - Herston
Recruitment hospital [3] 0 0
Investigational Site Number 0360005 - Murdoch
Recruitment hospital [4] 0 0
Investigational Site Number 0360001 - Parkville
Recruitment hospital [5] 0 0
Investigational Site Number 0360003 - Prahran
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
6150 - Murdoch
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment postcode(s) [5] 0 0
3004 - Prahran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Kentucky
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Utah
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
United States of America
State/province [13] 0 0
Wisconsin
Country [14] 0 0
Argentina
State/province [14] 0 0
Buenos Aires
Country [15] 0 0
Argentina
State/province [15] 0 0
Caba
Country [16] 0 0
Argentina
State/province [16] 0 0
Mendoza
Country [17] 0 0
Argentina
State/province [17] 0 0
Rosario
Country [18] 0 0
Argentina
State/province [18] 0 0
San Miguel De Tucumán
Country [19] 0 0
Belgium
State/province [19] 0 0
Bruxelles
Country [20] 0 0
Belgium
State/province [20] 0 0
Gent
Country [21] 0 0
Belgium
State/province [21] 0 0
Leuven
Country [22] 0 0
Canada
State/province [22] 0 0
Kingston
Country [23] 0 0
Canada
State/province [23] 0 0
Montreal
Country [24] 0 0
Canada
State/province [24] 0 0
Ottawa
Country [25] 0 0
Canada
State/province [25] 0 0
Quebec
Country [26] 0 0
Canada
State/province [26] 0 0
Trois-Rivieres
Country [27] 0 0
Canada
State/province [27] 0 0
Vancouver
Country [28] 0 0
Chile
State/province [28] 0 0
Quillota
Country [29] 0 0
Chile
State/province [29] 0 0
San Fernando
Country [30] 0 0
Chile
State/province [30] 0 0
Santiago
Country [31] 0 0
Chile
State/province [31] 0 0
Talca
Country [32] 0 0
Chile
State/province [32] 0 0
Viña Del Mar
Country [33] 0 0
Israel
State/province [33] 0 0
Hadera
Country [34] 0 0
Israel
State/province [34] 0 0
Nahariya
Country [35] 0 0
Israel
State/province [35] 0 0
Petah-Tikva
Country [36] 0 0
Israel
State/province [36] 0 0
Rehovot
Country [37] 0 0
Israel
State/province [37] 0 0
Tel Hashomer
Country [38] 0 0
Japan
State/province [38] 0 0
Bunkyo-Ku
Country [39] 0 0
Japan
State/province [39] 0 0
Chiyoda-Ku
Country [40] 0 0
Japan
State/province [40] 0 0
Fukuoka-Shi
Country [41] 0 0
Japan
State/province [41] 0 0
Hirakata-Shi
Country [42] 0 0
Japan
State/province [42] 0 0
Hiroshima-Shi
Country [43] 0 0
Japan
State/province [43] 0 0
Iida-Shi
Country [44] 0 0
Japan
State/province [44] 0 0
Inzai-Shi
Country [45] 0 0
Japan
State/province [45] 0 0
Itabashi-Ku
Country [46] 0 0
Japan
State/province [46] 0 0
Izumisano-Shi
Country [47] 0 0
Japan
State/province [47] 0 0
Kawasaki-Shi
Country [48] 0 0
Japan
State/province [48] 0 0
Kitakyushu-Shi
Country [49] 0 0
Japan
State/province [49] 0 0
Kumamoto-Shi
Country [50] 0 0
Japan
State/province [50] 0 0
Kyoto-Shi
Country [51] 0 0
Japan
State/province [51] 0 0
Meguro-Ku
Country [52] 0 0
Japan
State/province [52] 0 0
Moriguchi-Shi
Country [53] 0 0
Japan
State/province [53] 0 0
Okayama-Shi
Country [54] 0 0
Japan
State/province [54] 0 0
Osaka-Shi
Country [55] 0 0
Japan
State/province [55] 0 0
Ota-Ku
Country [56] 0 0
Japan
State/province [56] 0 0
Sendai-Shi
Country [57] 0 0
Japan
State/province [57] 0 0
Shimonoseki-Shi
Country [58] 0 0
Japan
State/province [58] 0 0
Shinagawa-Ku
Country [59] 0 0
Japan
State/province [59] 0 0
Shinjyuku-Ku
Country [60] 0 0
Japan
State/province [60] 0 0
Takatsuki-Shi
Country [61] 0 0
Japan
State/province [61] 0 0
Yoshida-Gun
Country [62] 0 0
Mexico
State/province [62] 0 0
Chihuahua
Country [63] 0 0
Mexico
State/province [63] 0 0
Durango
Country [64] 0 0
Mexico
State/province [64] 0 0
Guadalajara
Country [65] 0 0
Mexico
State/province [65] 0 0
Monterrey
Country [66] 0 0
Portugal
State/province [66] 0 0
Aveiro
Country [67] 0 0
Portugal
State/province [67] 0 0
Guimarães
Country [68] 0 0
Portugal
State/province [68] 0 0
Lisboa
Country [69] 0 0
Portugal
State/province [69] 0 0
Matosinhos
Country [70] 0 0
Portugal
State/province [70] 0 0
Porto
Country [71] 0 0
Portugal
State/province [71] 0 0
Viana Do Castelo
Country [72] 0 0
Russian Federation
State/province [72] 0 0
Moscow
Country [73] 0 0
Russian Federation
State/province [73] 0 0
Odintsovo
Country [74] 0 0
Russian Federation
State/province [74] 0 0
Saint-Petersburg
Country [75] 0 0
Russian Federation
State/province [75] 0 0
Stavropol
Country [76] 0 0
Russian Federation
State/province [76] 0 0
Yaroslavl
Country [77] 0 0
Spain
State/province [77] 0 0
Barcelona
Country [78] 0 0
Spain
State/province [78] 0 0
Jerez De La Frontera
Country [79] 0 0
Spain
State/province [79] 0 0
Madrid
Country [80] 0 0
Spain
State/province [80] 0 0
Sevilla
Country [81] 0 0
Spain
State/province [81] 0 0
Valencia
Country [82] 0 0
Sweden
State/province [82] 0 0
Lund
Country [83] 0 0
Sweden
State/province [83] 0 0
Stockholm
Country [84] 0 0
Turkey
State/province [84] 0 0
Ankara
Country [85] 0 0
Turkey
State/province [85] 0 0
Bursa
Country [86] 0 0
Turkey
State/province [86] 0 0
Istanbul
Country [87] 0 0
Turkey
State/province [87] 0 0
Izmir
Country [88] 0 0
Turkey
State/province [88] 0 0
Rize

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Sanofi
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Regeneron Pharmaceuticals
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Not available for request


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02898454