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A Controlled Clinical Study of Dupilumab in Patients With Nasal Polyps (SINUS-24)

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ClinicalTrials.gov Identifier: NCT02912468
Recruitment Status : Completed
First Posted : September 23, 2016
Last Update Posted : August 15, 2018
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

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 polyp 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 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 patients requiring treatment with systemic 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 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 residual effect in follow up.
  • 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.

Condition or disease Intervention/treatment Phase
Nasal Polyps Drug: Dupilumab SAR231893 (REGN668) Drug: Placebo Drug: Mometasone furoate nasal spray Phase 3

Detailed Description:
The total study duration per patient is expected to be up to 52 weeks that will consist of a 4-week run-in period, 24-week treatment period, and a 24-week posttreatment period.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 276 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Care Provider)
Primary Purpose: Treatment
Official Title: A Randomized, 24-Week Treatment, Double-blind, Placebo-controlled Efficacy and Safety Study of Dupilumab Every Other Week, in Patients With Bilateral Nasal Polyposis on a Background Therapy With Intranasal Corticosteroids
Study Start Date : December 5, 2016
Actual Primary Completion Date : July 5, 2018
Actual Study Completion Date : July 5, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Dupilumab

Arm Intervention/treatment
Experimental: Dupilumab (Arm A)
A dose of dupilumab will be administered subcutaneously (SC) every 2 weeks (q2w) up to Week 24. Patients will use MFNS daily.
Drug: Dupilumab SAR231893 (REGN668)

Pharmaceutical form: Solution

Route of administration: Subcutaneous


Drug: Mometasone furoate nasal spray

Pharmaceutical form: Suspension

Route of administration: Intranasal


Placebo Comparator: Placebo (Arm B)
A matching placebo will be administered subcutaneously (SC) every 2 weeks (q2w) up to Week 24. Patients will use MFNS daily.
Drug: Placebo

Pharmaceutical form: Solution

Route of administration: Subcutaneous


Drug: Mometasone furoate nasal spray

Pharmaceutical form: Suspension

Route of administration: Intranasal





Primary Outcome Measures :
  1. 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 ]
  2. Change from baseline in nasal polyposis score (NPS) as assessed by nasal endoscopy [ Time Frame: From baseline to Week 24 ]
  3. Change from baseline in sinus opacifications as assessed by computed tomography (CT) scans using Lund Mackay Score (For Japan only) [ Time Frame: From baseline to Week 24 ]

Secondary Outcome Measures :
  1. Change from baseline in total symptom score (TSS) (composite severity score consisting of the patient daily AM assessed NC, decreased/loss of sense of smell, anterior/posterior rhinorrhea) [ Time Frame: From baseline to Week 24 ]
  2. Change from baseline in University of Pennsylvania Smell Identification Test [ Time Frame: From baseline to Week 24 ]
  3. Change from baseline in severity of decreased/loss of smell as assessed by patient daily [ Time Frame: From baseline to Week 24 ]
  4. 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 ]
  5. Change from baseline in sinonasal outcome test-22 (SNOT-22) [ Time Frame: From baseline to Week 24 ]
  6. Proportion of patients during study treatment receiving systemic corticosteroid for NP and/or planned to undergo surgery for nasal polyps [ Time Frame: At Week 24 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 prior to 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 the 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 previously been 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 (IgE) 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 prior to 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 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.
  • Patients with nasal cavity malignant tumor and benign tumors (eg, papilloma, blood boil, etc).
  • Patients with forced expiratory volume in 1 second (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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02912468


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Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
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Study Director: Clinical Sciences & Operations Sanofi

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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02912468     History of Changes
Other Study ID Numbers: EFC14146
2015-003101-42 ( EudraCT Number )
U1111-1178-5390 ( Other Identifier: UTN )
First Posted: September 23, 2016    Key Record Dates
Last Update Posted: August 15, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Not yet available

Additional relevant MeSH terms:
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Polyps
Nasal Polyps
Pathological Conditions, Anatomical
Nose Diseases
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Mometasone Furoate
Antibodies, Monoclonal
Anti-Inflammatory Agents
Dermatologic Agents
Anti-Allergic Agents
Immunologic Factors
Physiological Effects of Drugs