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

Sanofi

Status and phase: Completed; Phase 3

Conditions: Chronic Rhinosinusitis Phenotype With Nasal Polyps (CRSwNP)

Treatments: Drug: Placebo; Drug: Mometasone furoate 50 micrograms; Drug: Dupilumab SAR231893 (REGN668)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02912468

EFC14146

U1111-1178-5390 (Other Identifier)

2015-003101-42 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 276 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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276 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Mometasone furoate 50 micrograms

Drug: Placebo

Dupilumab 300 mg

Experimental group

Description:

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.

Treatment:

Drug: Dupilumab SAR231893 (REGN668)

Drug: Mometasone furoate 50 micrograms