Dupilumab in Chinese Adult Participants With CRSwNP

Phase 3

Completed

Conditions: Chronic Rhinosinusitis With Nasal Polyps

Interventions: Drug: Placebo
Drug: Dupilumab
Drug: Budesonide

Registration Number: NCT05878093

Lead Sponsor: Sanofi

Brief Summary: This is a parallel group, Phase 3, 2-arm study for treatment. The purpose of this study is to evaluate dupilumab subcutaneous (SC) injections compared to placebo in Chinese adult participants with CRSwNP, on a background therapy with intranasal corticosteroids (budesonide nasal spray).

Study details include:

* The study duration will be up to 40 weeks.

* The treatment duration will be up to 24 weeks.

* The number of visits will be 7.

Detailed Description: up to 40 weeks

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 63

Inclusion Criteria

Participant must be at least 18 years of age at the time of signing the informed consent
Participants with bilateral sino-nasal polyposis that despite prior treatment with SCS anytime within the past 2 years; and/or who have a medical contraindication/intolerance to SCS; and/or had prior surgery for NP at Visit 1 have:
1. An endoscopic bilateral NPS at Visit 1 of at least 5 out of a maximum score of 8 (with a minimum score of 2 in each nasal cavity) as per central assessment
2. Ongoing symptoms (for at least 8 weeks before Visit 1) of:
  - Nasal congestion/blockade/obstruction with moderate or severe symptom severity (Score 2 or 3) at Visit 1 and a weekly average severity of greater than 1 at time of randomization (Visit 2) AND
  - Another symptom such as loss of smell, rhinorrhea (anterior/posterior)

Note: Plan to enroll at least 85% (approximately 52) participants with CRSwNP meeting following criterion:

• Participants with peripheral blood eosinophil count ≥300/mm3

Contraceptive use should be consistent with the regulations regarding the methods of contraception for those participating in clinical studies
Capable of giving signed informed consent

Exclusion Criteria

Participants with conditions/concomitant diseases making them non-evaluable at Visit 1 or for the primary efficacy endpoint (ie, NPS)
Participants with nasal cavity malignant tumor and benign tumors (eg, papilloma, hemangioma, etc)
Participant with historical spirometry results which showed 50% or less of predicted normal of forced expiratory volume in one second (FEV1)
Diagnosed with; suspected of, or at high risk of endoparasitic infection, and/or use of antiparasitic drug within 2 weeks before Visit 1 or during the screening period
History of human immunodeficiency virus infection or positive HIV 1/2 serology at Visit 1
Known or suspected immunodeficiency
Participants with active Tuberculosis (TB), non-tuberculous mycobacterial infection or a history of incompletely treated TB will be excluded from the study unless it is well documented by a specialist that the participant has been adequately treated and can now start treatment with a biologic agent, in the medical judgment of the Investigator and/or infectious disease specialist. Tuberculosis testing will be performed according to local guidelines if required by regulatory authorities or ethics boards, or if TB is suspected by the investigator
Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 2 weeks before Visit 1 or during the screening period
Active malignancy or history of malignancy within 5 years before the baseline visit, except completely treated in situ carcinoma of the cervix and completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin
Known or suspected alcohol and/or drug abuse
History of systemic hypersensitivity or anaphylaxis to dupilumab including any excipient
Participants meet any contraindications or warning on product labeling for budesonide nasal spray
Severe concomitant illness(es) that, in the Investigator's judgement, would adversely affect the participant's participation in the study.
Participants with any other medical or psychological condition including relevant laboratory or electrocardiogram (ECG) abnormalities at screening that, in the opinion of the Investigator, suggest a new and/or insufficiently understood disease, may present an unreasonable risk to the study participant as a result of his/her participation in this clinical trial, may make participant's participation unreliable, or may interfere with study assessments. The specific justification for participants excluded under this criterion will be noted in study documents (chart notes, case report form (CRF), etc)
Planned major surgical procedure during the participant's participation in this study
Participants who have taken:

Biologic therapy/systemic immunosuppressant/immunomodulator within 4 weeks before Visit 1 or 5 half-lives, whichever is longer.

Any investigational monoclonal antibody (mAb) within 5 half-lives or within 6 months before Visit 1 if the half-life is unknown.

Anti-immunoglobulin E therapy (omalizumab) within 4 months prior to Visit 1.

Treatment with a live (attenuated) vaccine within 4 weeks prior to Visit 1
Participants who are receiving leukotriene antagonists/modifiers within 4 weeks before V1 or 5 half-lives, whichever is longer, unless patient is on a continuous treatment for at least 4 weeks before Visit 1
Initiation of allergen immunotherapy within 3 months prior to Visit 1 or a plan to begin therapy or change its dose during the run-in or randomized treatment period
Participants who have undergone any intranasal and/or sinus surgery (including polypectomy) within 6 months prior to Visit 1 or sino-nasal surgery changing the lateral wall structure of the nose making the evaluation of NPS impossible
Use of any prohibited medications and procedures during screening period or planned use during screening or study treatment period
Either intravenous immunoglobulin (IVIG) therapy and/or plasmapheresis within 4 weeks before Visit 1
Current participation in any clinical trial of an investigational drug or device or participation within 3 months before V1 or 5 half-lives of the investigational compound, whichever is longer
Participation in a prior dupilumab clinical study or have been treated with commercially available dupilumab
Patients with any of the following result at the screening visit (Visit 1):

Positive (or indeterminate) hepatitis B surface antigen (HBsAg) or, Positive total Hepatitis B core antibody (HBc Ab) confirmed by positive hepatitis B virus (HBV) DNA or, Positive HCV Ab confirmed by positive hepatitis C Virus (HCV) RNA.

noninvestigational medicinal product(NIMP) noncompliance at Visit 2 (<80%)
Any condition that could make the participant noncompliant with the study procedures and daily assessment in the e-diary
Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized.
Participants not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures
Participants are employees of the clinical study site or other individuals directly involved in the conduct of the study, or immediate family members of such individuals
Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo matching dupilumab Q2W via SC injection
Dupilumab	Budesonide	Dupilumab every 2 weeks (Q2W) via SC injection
Dupilumab	Dupilumab	Dupilumab every 2 weeks (Q2W) via SC injection
Placebo	Budesonide	Placebo matching dupilumab Q2W via SC injection

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Nasal Polyps Score at Week 24	Baseline (Day 1) and Week 24	The NPS was the sum of the right and left nostril scores and assessed by central video recordings of bilateral nasal endoscopy. For each nostril, NPS was graded based on polyp size which ranged from 0: no polyps, 1: small polyps in the middle meatus not reaching below the inferior border of the middle turbinate, 2: polyps reaching below the lower border of the middle turbinate, 3: large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle turbinate, 4: large polyps causing complete obstruction of the inferior nasal cavity. Total NPS was the sum of right and left nostril scores; ranged from 0 (no polyps) to 8 (large polyps). Higher scores indicated more severe disease. Baseline was defined as the last available value before randomization.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Nasal Congestion/Obstruction Score (NCS) at Week 24	Baseline (Day -7 to Day -1) and Week 24	The NCS was a patient reported outcome to evaluate nasal congestion/obstruction, a major clinical symptom in chronic rhinosinusitis phenotype with nasal polyps. The NCS was assessed by the participant on a daily basis from visit 1 and throughout the study. It consisted of a 0 to 3 categorical scale, where 0: no symptoms, 1: mild symptoms, 2: moderate symptoms and 3: severe symptoms. Higher scores indicated more severity. The Week 24 analysis score was calculated as the average of all scores during the 4 weeks before Week 24. Baseline was defined as the average of the scores in the 7 days prior to randomization.
Change From Baseline in Total Symptoms Score (TSS) at Week 24	Baseline (Day -7 to Day -1) and Week 24	The TSS was a reflective score of the worst symptom severity over the past 24 hours by the participant. It was assessed by the participant on a daily basis from visit 1 and throughout the study. It consisted of the sum of the following rhinosinusitis symptom questions: nasal congestion, decreased/loss of sense of smell, rhinorrhea (average of anterior/posterior nasal discharge); each assessed on 0 to 3 categorical scale, where 0: no symptoms, 1: mild symptoms, 2: moderate symptoms and 3: severe symptoms. The TSS was a composite score by summing the above symptom scores and ranged from 0 (no symptoms) to 9 (severe symptoms). Higher scores indicated greater overall symptom severity. The Week 24 analysis score was calculated as the average of all scores during the 4 weeks before Week 24. Baseline was defined as the average of the scores in the 7 days prior to randomization.
Change From Baseline in Total Score of 22-Items Sinonasal Outcome Test (SNOT-22) at Week 24	Baseline (Day 1) and Week 24	The SNOT-22 was a validated 22-items questionnaire to assess the impact of chronic rhinosinusitis on health-related quality of life (HRQoL) with a recall period of 2 weeks. There were 5 domains that could be described within SNOT-22, including nasal, ear, sleep, general and practical, and emotional; each domain was scored on a 5-category scale which ranged from 0: no problem to 5: problem as bad as it can be. The total score was the sum of response to each of the 22 questions and ranged from 0 (no disease) to 110 (worst disease), higher scores indicated worse HRQoL. Baseline was defined as the last available value before randomization.
Percentage of Participants Who Received Systemic Corticosteroid (SCS) or Underwent Nasal Polyposis (NP) Surgery During the Study Treatment	From randomization (Day 1) up to last dose of study treatment + 14 days, a maximum of 168 days	SCS for rescue treatment of nasal polyps or for another reason were prescribed to the participant by the site. For participants who had a surgery or had a scheduled date for surgery for NP, the reason (worsening signs and/or symptoms during the study), the expected or actual surgery date, the type and outcome of surgery was recorded in a specific e-case report form page. Percentage of participants who received SCS or underwent NP surgery during the study treatment are presented.
Change From Baseline in the Severity of Decreased/Loss of Smell at Week 24	Baseline (Day -7 to Day -1) and Week 24	The decreased/loss of sense of smell severity was a reflective score of the worst symptom severity over the past 24 hours. It was assessed by the participant on a daily basis from visit 1 and throughout the study, using an e-diary. It consisted of a 0 to 3 categorical scale, where 0: no symptoms, 1: mild symptoms, 2: moderate symptoms and 3: severe symptoms. Higher scores indicated more severe symptoms. The Week 24 analysis score was calculated as the average of all scores during the 4 weeks before Week 24. Baseline was defined as the average of the scores in the 7 days prior to randomization.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Treatment-Emergent Adverse Events Leading to Treatment Discontinuation	From first dose of study treatment (Day 1) up to last dose of study treatment + 98 days, a maximum of 252 days	An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. TEAEs were defined as AEs that developed, worsened or became serious during the TE period.

Trial Locations

Locations (18): Investigational Site Number : 1560005
🇨🇳
Beijing, China
Investigational Site Number : 1560001
🇨🇳
Beijing, China
Investigational Site Number : 1560010
🇨🇳
Chengdu, China
Investigational Site Number : 1560014
🇨🇳
Chongqing, China
Investigational Site Number : 1560022
🇨🇳
Fuzhou, China
Investigational Site Number : 1560012
🇨🇳
Guangzhou, China
Investigational Site Number : 1560011
🇨🇳
Guangzhou, China
Investigational Site Number : 1560004
🇨🇳
Hangzhou, China
Investigational Site Number : 1560006
🇨🇳
Hefei, China
Investigational Site Number : 1560016
🇨🇳
Jinan, China
Scroll for more (8 remaining)
Investigational Site Number : 1560005
🇨🇳Beijing, China