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Controlled Clinical Study of Dupilumab in Patients With Nasal Polyps (SINUS-52)

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ClinicalTrials.gov Identifier: NCT02898454
Recruitment Status : Completed
First Posted : September 13, 2016
Last Update Posted : November 26, 2018
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE September 8, 2016
First Posted Date  ICMJE September 13, 2016
Last Update Posted Date November 26, 2018
Actual Study Start Date  ICMJE November 28, 2016
Actual Primary Completion Date August 27, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 22, 2017)
  • Change from baseline in nasal congestion/obstruction (NC) symptom severity score based on the patient daily morning assessment [ Time Frame: From baseline to Week 24 ]
  • Change from baseline in nasal polyposis score (NPS) as assessed by nasal endoscopy [ Time Frame: From baseline to Week 24 ]
  • Change from baseline in sinus opacifications as assessed by CT scans using Lund Mackay Score (For Japan only) [ Time Frame: From baseline to Week 24 ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 8, 2016)
  • Change from baseline in NC symptom severity score based on the patient daily morning assessment [ Time Frame: From baseline to Week 24 ]
  • Change from baseline in NPS as assessed by nasal endoscopy [ Time Frame: From baseline to Week 24 ]
  • Change from baseline in sinus opacifications as assessed by CT scans using Lund Mackay Score (For Japan only) [ Time Frame: From baseline to Week 24 ]
Change History Complete list of historical versions of study NCT02898454 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 22, 2017)
  • Change from baseline in TSS [ Time Frame: From baseline to Week 24 ]
  • Change from baseline in University of Pennsylvania Smell Identification Test [ Time Frame: From baseline to Week 24 ]
  • Change from baseline in severity of decreased/ loss of smell as assessed by the patient [ Time Frame: From baseline to Week 24 ]
  • Change from baseline in sinus opacifications as assessed by CT scans using Lund Mackay Score (This endpoint will not be assessed as a secondary endpoint for Japan as it is already a co-primary endpoint). [ Time Frame: From baseline to Week 24 ]
  • Change from baseline in in sinonasal outcome test-22 (SNOT-22) [ Time Frame: From baseline to Week 24 ]
  • Proportion of patients during study treatment receiving systemic corticosteroid for NP and/or planned to under surgery for nasal polyps [ Time Frame: 52 Weeks ]
  • Change from baseline in NC for every two weeks (q2w) (Arm A) versus placebo (Arm C) [ Time Frame: From baseline to Week 52 ]
  • Change from baseline in NPS for q2w (Arm A) versus placebo (Arm C) [ Time Frame: From baseline to Week 52 ]
  • Change from baseline in NC for q2w/q4w (Arm B) versus placebo (Arm C) [ Time Frame: From baseline to Week 52 ]
  • Change from baseline in NPS for q2w/q4w (Arm B) versus placebo (Arm C) [ Time Frame: From baseline to Week 52 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 8, 2016)
  • Change from baseline in TSS [ Time Frame: From baseline to Week 24 ]
  • Change from baseline in University of Pennsylvania Smell Identification Test [ Time Frame: From baseline to Week 24 ]
  • Change from baseline in severity of decreased/ loss of smell as assessed by the patient [ Time Frame: From baseline to Week 24 ]
  • Change from baseline in sinus opacifications as assessed by CT scans using Lund Mackay Score (This endpoint will not be assessed as a secondary endpoint for Japan as it is already a co-primary endpoint). [ Time Frame: From baseline to Week 24 ]
  • Change from baseline in in sinonasal outcome test-22 (SNOT-22) [ Time Frame: From baseline to Week 24 ]
  • Proportion of patients during study treatment receiving oral corticosteroid (OCS) for NP and/or planned to under surgery for nasal polyps [ Time Frame: 52 Weeks ]
  • Change from baseline in NC for q2w (Arm A) versus placebo (Arm C) [ Time Frame: From baseline to Week 52 ]
  • Change from baseline in NPS for q2w (Arm A) versus placebo (Arm C) [ Time Frame: From baseline to Week 52 ]
  • Change from baseline in NC for q2w/q4w (Arm B) versus placebo (Arm C) [ Time Frame: From baseline to Week 52 ]
  • Change from baseline in NPS for q2w/q4w (Arm B) versus placebo (Arm C) [ Time Frame: From baseline to Week 52 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Controlled Clinical Study of Dupilumab in Patients With Nasal Polyps
Official Title  ICMJE 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
Brief Summary

Primary Objective:

To evaluate the efficacy of dupilumab compared to placebo on a background of mometasone furoate nasal spray (MFNS) in reducing nasal congestion/obstruction (NC) severity and endoscopic nasal polyposis score (NPS) in patients with bilateral nasal polyposis (NP). In addition for Japan, reduction in computed tomography (CT) scan opacification of the sinuses will be also a co-primary 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 patients requiring treatment with oral corticosteroids or NP surgery.
  • To evaluate the effect of dupilumab on patient reported outcomes and health related quality of life outcome by sinonasal outcome test-22 (SNOT-22).
  • To evaluate efficacy with various regimen.
  • To evaluate the effect of dupilumab in the subgroups of patients with prior surgery and co-morbid asthma (including non-steroid antiinflammatory drug [NSAID] exacerbated respiratory disease [NERD]).
  • To evaluate the safety of dupilumab in patients with bilateral NP.
  • To evaluate functional dupilumab concentrations (systemic exposure) and incidence of treatment-emergent anti-drug antibodies (ADA).
Detailed Description The total study duration per patient is expected to be up to 68 weeks that will consist of a 4-week run-in period, 52-week treatment period, and a 12-week posttreatment period.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Nasal Polyps
Intervention  ICMJE
  • Drug: Dupilumab SAR231893 (REGN668)

    Pharmaceutical form: Solution

    Route of administration: Subcutaneous

  • Drug: Placebo

    Pharmaceutical form: Solution

    Route of administration: Subcutaneous

  • Drug: Mometasone furoate nasal spray

    Pharmaceutical form: Suspension

    Route of administration: Intranasal

Study Arms  ICMJE
  • Experimental: Dupilumab (Arm A)
    A dose of dupilumab will be administered subcutaneously (SC) every 2 weeks (q2w) until Week 52. Patients will use MFNS daily.
    Interventions:
    • Drug: Dupilumab SAR231893 (REGN668)
    • Drug: Mometasone furoate nasal spray
  • Experimental: Dupilumab (Arm B)
    A dose of dupilumab will be administered SC every 2 weeks until Week 24, then every 4 weeks (q4w) until Week 52. Patients will use MFNS daily.
    Interventions:
    • Drug: Dupilumab SAR231893 (REGN668)
    • Drug: Mometasone furoate nasal spray
  • Placebo Comparator: Placebo (Arm C)
    A matching placebo will be administered SC every 2 weeks (q2w) until Week 52. Patients will use MFNS daily.
    Interventions:
    • Drug: Placebo
    • Drug: Mometasone furoate nasal spray
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 23, 2018)
448
Original Estimated Enrollment  ICMJE
 (submitted: September 8, 2016)
360
Actual Study Completion Date  ICMJE November 16, 2018
Actual Primary Completion Date August 27, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria :

  • Patients with bilateral sinonasal polyposis that despite prior treatment with systemic corticosteroids (SCS) anytime within the past 2 years; and/or have a medical contraindication/intolerance to SCS; and/or had prior surgery for NP at the screening visit, have:
  • 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 before V1) 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 time of randomization (V2), and another symptom such as loss of smell, rhinorrhea (anterior/posterior).
  • Signed written informed consent.

Exclusion criteria:

  • Patients <18 years of age.
  • Patient who has been previously treated in dupilumab studies.
  • Patient who has 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 is longer.
  • Any experimental monoclonal antibody (mAB) within 5 half-lives or within 6 months before V1 if the half-life is unknown.
  • Anti-immunoglobulin E therapy (omalizumab) within 130 days prior to V1.
  • Patients who are receiving leukotriene antagonists/modifiers at V1 unless they are 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.
  • Patients who have undergone any intranasal and/or sinus surgery (including polypectomy) within 6 months before V1.
  • Patients who have had a sinonasal or sinus surgery changing the lateral wall structure of the nose making impossible the evaluation of NPS.
  • Patients 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.
  • Patients with nasal cavity malignant tumor and benign tumors (eg, papilloma, blood boil etc.).
  • Patients with forced expiratory volume (FEV1) 50% or less (of predicted normal).
  • Patients receiving 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 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 is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Chile,   Russian Federation,   Argentina,   Australia,   Belgium,   Canada,   Israel,   Japan,   Mexico,   Portugal,   Spain,   Sweden,   Turkey,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02898454
Other Study ID Numbers  ICMJE EFC14280
2015-001314-10 ( EudraCT Number )
U1111-1170-7180 ( Other Identifier: UTN )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Not available for request
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Regeneron Pharmaceuticals
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP