Dupixent Study for Alternate Administration

Phase 4

Active, not recruiting

• Conditions: Nasal Polyps; Sinusitis; Chronic Disease
• Interventions: Biological: Dupilumab

• Registration Number: NCT06750471
• Lead Sponsor: Madigan Army Medical Center

Brief Summary

Investigators will investigate an alternate Dupilumab administration schedule in patients with recurrent chronic rhinosinusitis with nasal polyposis, who have a history of full endoscopic sinus surgery and are on appropriate topical medical therapies. Specifically, investigators will investigate if the alternate schedule of drug administration is non-inferior in both subjective and objective outcomes.

Detailed Description

Dupixent was recently approved by the FDA for chronic rhinosinusitis patients with nasal polyposis in April 2019. Literature support for this approval comes from results obtained from a landmark Phase III trial (LIBERTY SINUS-24 and SINUS-52) that were published in November 2019. The data suggests that Dupilumab improves subjective quality of life significantly in patients with chronic sinusitis with nasal polyposis and there is objective evidence of decreased disease burden and severity of other comorbidities (asthma, aspirin exacerbated respiratory disease). Therefore, there is robust scientific evidence supporting the use of this medication in chronic rhinosinusitis with nasal polyposis patients along with the FDA indication for usage of this medication in this subset of patients.

Otolaryngologists see and manage most (if not all) of chronic sinusitis patients with persistent symptoms and give recommendations for surgical and medical therapies. Given our unique ability to perform a detailed examination and provide medical and surgical care, investigators believe that this patient population will be best served with us making the determination of when to initiate the treatment if other treatment strategies fail. Given the cost associated with this medication (\~ $45,630/patient/year based on price of $1,755/injection), investigators can make the judicious determination for when to prescribe this medication based on published evidence and guidelines in literature.

After careful assessment of LIBERTY study, most subjective and objective outcomes appear to show statistically and clinically significant benefit after 8 weeks of therapy. Moreover, one of the study arms had patients on this medication every 2 weeks until 26 weeks and then switched to every 4 weeks for the rest of the year. Given the apparent benefit of medication compared to placebo at 8 weeks, investigators propose that an alternate medication schedule with less frequent dosing after 8 weeks will be just as effective in improving subjective and objective outcomes in this patient population. If a non-inferior improvement is noted in the alternate medication schedule, then this will translate into significant cost saving to DoD and DHA (\~$21,000/patient/year) when patients are placed on this medication due to the refractory nature of their disease.

Moreover, if the alternate schedule is just as effective, then this will validate use of this schedule in active duty service members (ADSM) during temporary duty or deployments to keep them medically fit and ready. Although topical steroid rinses are beneficial after surgery, the lack of distilled water in some austere environments prohibit usage and some patients have disease recurrence despite steroids and therefore require alternate medications or additional surgery. If the alternate regimen is proven to be non-inferior, then ADSMs or their medical team can carry the pre-made medication with them while following appropriate storage instructions according to drug information. Based on the FDA information website, Dupilumab can be stored below the room temperature (\<77F or \<25C) in pre-filled syringes up to 14 days or within refrigerator (between 2-8 C) until expiration. As long as these storage conditions can be met, ADSMs can continue this regimen while they are away. Additionally, if they are stable on long term Dupilumab therapy, there is potential for even longer time intervals between injections to help manage their chronic disease process.

Study Timeline

• Study First Submitted: 2021-08-30
• Study Start: 2021-10-14
• Study First Submitted QC: 2024-12-19
• Study First Posted: 2024-12-27
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-16
• Last Update Posted: 2025-01-17
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

• Previous use of other biologic therapy in last 6 months
• if history of asthma, FEV1< 50%
• history of cystic fibrosis, eosinophilic granulomatosis with polyangiitis, granulomatosis with polyangiitis, kartagener syndrome, primary ciliary dyskinesia
• Patient is a pregnant woman, may become pregnant or breastfeeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A - Regular Adminstration	Dupilumab	Eligible patient will receive 300 mg Subcutaneous Dupilumab every 2 weeks for 28 weeks
Arm B - Alternate Administration	Dupilumab	Eligible patient will receive 300 mg Subcutaneous Dupilumab every 2 weeks for 8 weeks and then every 4 weeks up until 28 weeks

Primary Outcome Measures

Name	Time	Method
Change in Sinonasal outcome test - 22 over different time intervals	Baseline, week 4, week 8, week 16 and week 28	22 item questionnaire of impact of chronic rhinosinusitis on quality of life. Scored from 0-120: higher number = worse symptoms
Change in Lund Kennedy Score over different time intervals	Baseline, week 4, week 8, week 16 and week 28	Sinus endoscopy to objectively score the impact of drug on patient's disease process. Total points = 20 (10 on each side), higher score = worse objective data
Change in Total polyp score over different time intervals	Baseline, week 4, week 8, week 16 and week 28	Sinus endoscopy to objectively score the impact of drug on patient's disease process. Scored from 0-8, 4 on each side. Higher scores = worse polyp scores
Change in Rhinosinusitis Disability Index Score (RSDI) over different time intervals	Baseline, week 4, week 8, week 16 and week 28	Disability associated with chronic rhinosinusitis, Scored from 0-120: higher number = worse quality of life.

Secondary Outcome Measures

Name	Time	Method
Change in IgE levels over different time intervals	Baseline, week 4, week 8, week 16 and week 28	Labs to evaluate the impact of Dupilimab administration in patients
Change in Eosinophil levels over different time intervals	Baseline, week 4, week 8, week 16 and week 28	Labs to evaluate the impact of Dupilimab administration in patients
Cost Savings between 2 treatment arms	Ove the course of the study timeline - 28 weeks	Cost savings between the two treatment arms will be compared to see how cost to healthcare was saved with alternate therapy.
Need for additional interventions or surgeries in each arm	Over the course of the study timeline - 28 weeks	We will assess if participants needed oral steroids or surgeries while being on dupixent therapy over the course of study to help manage their symptoms.

Trial Locations

Locations (1)

Madigan Army Medical Center; 🇺🇸 Tacoma, Washington, United States