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Allergic Fungal Rhinosinusitis (AFRS)Phase 3NCT06461949

Study of Dupilumab 300 mg Every Other Week After Endoscopic Sinus Surgery in Patients With Allergic Fungal Rhinosinusitis (AFRS) on a Background Therapy With Intranasal Corticosteroid Spray

A Phase 3 study testing Dupilumab in people with Allergic Fungal Rhinosinusitis (AFRS) and Chronic Rhinosinusitis (CRS), run by National Institute on Deafness and Other Communication Disorders (NIDCD).

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

Background: Allergic fungal rhinosinusitis (AFRS) is a severe type of sinus infection. People with AFRS develop heavy mucus and growths called polyps that apply pressure to the sinuses and block their breathing. Surgery can remove the polyps, but they often grow back. Read more about this study

Who is it for?
Ages 18 to 99 years
What is being tested?
Dupilumab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
No sites listed yet
Study dates
17 Jul 2024to 17 Jul 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants are eligible for study participation if all inclusion and no exclusion criteria are met. Non- English-speaking people will be included if they fulfill the criteria. In order to be eligible to participate in this study, an individual must meet all of the following criteria:
  • Informed consent
  • Participants must be capable of giving signed informed consent as listed in the informed consent form (ICF) and this protocol.
  • ICF must be signed and dated prior to study specific procedures. Informed consent process is described further below.
  • Age
  • -Participants aged >=18 years at the time of signing the ICF.
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  • Types of subject and disease characteristics
  • Participants with nasal polyps in the setting of suspected AFRS and electing to undergo comprehensive sinus surgery per established criteria.
  • Diagnosis of nasal polyps by consensus criteria.
  • Failure of appropriate medical therapy, including topical intranasal corticosteroid (spray or irrigation) > 8 weeks duration, systemic corticosteroid trial of 1-3 weeks duration and nasal saline irrigation of > 4 weeks duration.
  • A minimum SNOT-22 score of 20 at time of enrollment.
  • A minimum CT Lund-MacKay score of > 1 at time of enrollment.
  • Suspected AFRS based on Bent and Kuhn criteria
  • Participants must meet 3/5 criteria at time of enrollment
  • Environmental atopy by skin or serum testing
  • Nasal polyposis
  • Characteristic CT findings
  • Eosinophilic mucous
  • Fungal identification on histopathology
  • Participants must meet 5/5 criteria at time of randomization.
  • Enrolled subjects are expected to undergo SoC allergy testing and sinus surgery prior to randomization. This will complete evaluation for suspected AFRS, thus enabling further study participation. Allergy testing \& sinus surgery, in addition to other SoC items, will be done per clinical guidelines at the treating institution and will not be covered in this protocol.
  • Sinus Surgery
  • -All study participants will have met criteria for sinus surgery and undergo a comprehensive procedure prior to randomization. The procedure will not be assigned and will be completed per SoC at the treating institution for the management of nasal polyps in suspected AFRS.
  • Reproduction
  • Negative urine pregnancy test will be required at enrollment and study visits 3, 4, 5 and 6, throughout the treatment period for participants of childbearing potential (i.e., post-pubescent, premenopausal females).
  • Persons of childbearing potential must use an effective form of birth control (confirmed by the Investigator) e.g., total sexual abstinence, vasectomized sexual partner, tubal occlusion, intrauterine device or levonorgestrel Intrauterine system, Depo-Provera injections, oral contraceptive, Evra Patch, or Nuvaring. Women of childbearing potential must agree to use a highly effective method of birth control, as defined above, from enrollment, throughout the study duration and for 12 weeks after the last dose of IMP.
  • To protect against possible side effects, men should not get a sexual partner pregnant while taking the study drug and for 12 weeks after the last dose. Men should agree on a method of birth control to use throughout the study.

Who cannot join

  • An individual who meets any of the following criteria will be excluded from participation in this study:
  • Medical Conditions:
  • Participants who have undergone nasal or sinus surgery within 3 months prior to enrollment.
  • Participants with conditions or comorbid disease findings that preclude nasal endoscopy for evaluation of primary outcome, such as:
  • Current rhinitis medicamentosa
  • Nasal cavity tumors
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  • Occlusive septal deviation following surgery
  • Clinically important comorbidities that may confound interpretation of clinical efficacy, including:
  • Aspirin-exacerbated respiratory disease
  • Cystic fibrosis
  • Primary ciliary dyskinesia
  • Hereditary Hemorrhagic Telangiectasia
  • Antrochoanal polyposis
  • Non-asthma eosinophilic disease, such as bronchopulmonary aspergillosis, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome
  • Granulomatosis with polyangiitis
  • Any corticosteroid dependent condition
  • A comorbid health disorder that is not medically controlled in the opinion of the Investigator, and has the potential to:
  • Affect the safety of the subject throughout the study
  • Impede the subject s ability to complete the duration of the study
  • Influence the primary or secondary outcomes of the study
  • Participant experiencing a symptomatic asthma exacerbation requiring systemic corticosteroids or hospitalization (>24 hours) within 4 weeks of randomization.
  • Infection requiring systemic antibiotics within 4 weeks of randomization.
  • --Parenteral and/or oral antibiotics associated with surgery are allowed
  • Medical contraindication to receiving dupilumab:
  • Known hypersensitivity to dupilumab or any of its excipients
  • Live vaccine administration within 30 days of randomization or during study period
  • Known helminth infection.
  • Unable to tolerate sinonasal irrigations.
  • Pregnancy, current lactation, or lack of effective contraception plan, as determined by the site investigator.
  • Prior Concomitant Therapy
  • Initiation of allergen immunotherapy within 3 months prior to randomization or a plan to begin therapy or change its dose during the study period.
  • Immunosuppressive medication within 3 months prior to randomization and during the study period from randomization through EOS.
  • Receipt of any marketed or investigational biologic products (monoclonal or polyclonal antibody) within 6 months or 5 half-lives, whichever is longer, prior to randomization during the study period.
  • Previous use of dupilumab.
  • Receipt of immunoglobulin or blood products within 30 days prior to randomization.
  • Receipt of any investigational drug within 30 days or 5 half-lives, whichever is longer prior to randomization.
  • Scheduled systemic corticosteroid treatment during the study period:
  • --Standardized corticosteroid taper associated with planned surgery is allowed.
  • Receipt of leukotriene antagonists or modifiers for participants who were not on a stable dose for > 30 days prior to randomization
  • Prior/concurrent clinical study experience
  • -Concurrent enrollment in another investigational drug trial during the study period.
  • Other Exclusions
  • Participant involvement in the planning or conduct of the study.
  • Investigator assessment that the subject is unlikely to comply with study procedures.
  • Prior randomization in the present study.

About this study

Official title: A Randomized, 52-Week Treatment Double-Blind, Placebo-Controlled Efficacy and Safety Study of Dupilumab 300 mg Every Other Week After Endoscopic Sinus Surgery in Patients With Allergic Fungal Rhinosinusitis (AFRS) on a Background Therapy With Intranasal Corticosteroid Spray

Background:

Allergic fungal rhinosinusitis (AFRS) is a severe type of sinus infection. People with AFRS develop heavy mucus and growths called polyps that apply pressure to the sinuses and block their breathing. Surgery can remove the polyps, but they often grow back. Researchers want to test an approved drug they believe may help people with AFRS.

Read more

Objective:

To test a drug (Dupilumab) in people with AFRS.

Eligibility:

People aged 18 years or older with suspected AFRS who are scheduled to undergo surgery for nasal polyps.

Design:

Participants will have several tests before their surgery. They will have imaging scans of their sinuses. They will have an endoscopic exam: A tube with a camera and a light will be inserted into their sinuses. They may give blood and mucus samples. They will have standard treatment with nasal sprays for 2 to 6 weeks before their surgery.

Excess nasal tissue removed during the surgery will be collected for research. Then they will begin treatment with the study drug.

Dupilumab is injected under the skin. Some participants will receive the study drug. Some will receive a placebo injections. The placebo injections are just like the study drug but contain no medicine. Participants will not know which injections they are getting.

All participants will administer the injections to themselves at home. They will do this every 2 weeks for 1 year after the surgery. They will have a clinic visit 16 weeks after surgery.

Participants will have follow-up for 12 weeks after treatment ends.

Read the detailed description

Study Description:

Multicenter, randomized, double-blind, placebo-controlled study comparing the efficacy of dupilumab to placebo in allergic fungal rhinosinusitis (AFRS) subjects after sinus surgery on a background treatment with intranasal corticosteroid spray.

Study periods:

The clinical trial consists of 4 periods:

-Run-in period (2 weeks + 4 weeks):

All participants will enter a run-in period of 2-6 weeks receiving saline irrigations and Intranasal Corticosteroids per the treating physician. All oral steroids and antibiotics will be stopped.

-Ethmoid Tissue Collection period (7 days + 4 weeks):

Participants will undergo surgery as scheduled per standard of care. Ethmoid tissue will be collected from all subjects at the time of surgery.

-Randomized treatment (52 weeks +/- 7 days):

Participants will be randomized to one of the following treatments:

  • Arm A: dupilumab 300 mg subcutaneous (SC) every two weeks for 52 weeks
  • Arm B: placebo given SC every two weeks for 52 weeks
  • Posttreatment period (12 weeks +/- 7 days):

After completing 52 weeks of treatment with IMP (or following early discontinuation of IMP), subjects will be instructed to:

  • Return to the study site for the last scheduled visits for physical examination, nasal endoscopy, Nasal Polyps Score (NPS), Patient-Reported Outcomes (PROs)(Sinonasal Outcomes Test-SNOT-22-, and Asthma Control Questionnaire -ACQ-), FEV1 measurement in those with asthma, and safety.
  • Continue on stable dose of INCS spray during the posttreatment period.
  • Report any adverse event (AE).

Co-Primary Objectives:

  • Determine the efficacy of dupilumab in controlling sinonasal inflammation and preventing nasal polyp recurrence after complete sinus surgery for AFRS as measured by change in the mLK score.
  • Evaluate the effect of dupilumab on oral corticosteroid utilization following complete sinus surgery for AFRS.

Secondary Objectives:

To evaluate the effect of dupilumab on:

  • Prevention of revision surgery for AFRS
  • Secondary objective measures of sinonasal inflammation following sinus surgery using NPS and LMS.
  • Lower airway dysfunction following sinus surgery in the subgroup of participants with asthma (approximately 25%)
  • Upper and lower airway, disease-specific, health-related quality of life, as measured by ACQ and SNOT-22
  • Reducing utilization of rescue medications for acute exacerbations of CRS following sinus surgery

Primary Endpoints:

Change from baseline at 52 weeks both within and between treatment and placebo arms:

  • Endoscopic modified Lund-Kennedy (mLK) score
  • Incidence of oral corticosteroid utilization per participant

Secondary Endpoints:

Change from baseline at 52 weeks both within and between treatment and placebo arms:

  • Prevalence of revision sinus surgery for recurrent nasal polyps, and comparison of survival curves
  • Endoscopic nasal polyp score (NPS)
  • CT generated Lund-McKay score
  • Spirometry (for participants with comorbid asthma)
  • 22-item sinonasal outcomes test (SNOT-22)
  • Asthma Control Questionnaire (ACQ)
  • Prevalence of oral / topical corticosteroid utilization per treatment cohort
  • Incidence of oral / topical antibiotic utilization per subject
  • Prevalence of oral / topical antibiotic utilization per treatment cohort
Being tested
Dupilumab
Keywords
Ethmoid tissue, Intranasal corticosteroids, Nasal polyps, Sinonasal inflammation, Lung Function, Quality of Life
Medical subject headings
Allergic Fungal Sinusitis, Asthma, Nasal Polyps

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DupilumabDrug

    Dupilumab (Dupixent) is a human monoclonal antibody administered via subcutaneous injection to treat various conditions such as Chronic Rhinosinusitis with Nasal Polyps, Asthma and Eosinophilic Esophagitis.

Study groups in NCT06461949
Study groupRoleWhat they receive
Arm A:ExperimentalTreatment: Dupilumab 300 mg administered subcutaneously every two weeks for 52 weeks.
Receives: Drug: Dupilumab
Arm B:Placebo comparatorControl: Placebo administered subcutaneously every two weeks for 52 weeks.
Receives: Drug: Dupilumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Efficacy of Dupilumab

    -Control of sinonasal inflammation.-Prevention of nasal polyp recurrence after complete sinus surgery for AFRS.-Measured by change in the modified Lund-Kennedy (mLK) score.

    Measured: Change from baseline at 52 weeks

Secondary outcomes (6)
  1. Effect of Dupilumab on Oral Corticosteroid Utilization

    Reduction in the use of oral corticosteroids following complete sinus surgery for AFRS.

    Measured: Change from baseline at 52 weeks

  2. Prevention of Revision Surgery for AFRS

    Assessment of the need for additional surgery due to recurrent nasal polyps.

    Measured: Change from baseline at 52 weeks

  3. Secondary Objective Measures of Sinonasal Inflammation

    Changes in nasal polyp score (NPS) and CT-generated Lund-McKay score (LMS).

    Measured: Change from baseline at 52 weeks

  4. Lower Airway Dysfunction in Participants with Asthma

    Spirometry measurements and other assessments in approximately 25% of participants with asthma

    Measured: Change from baseline at 52 weeks

  5. Health-Related Quality of Life

    Upper and lower airway disease-specific quality of life measured by the Asthma Control Questionnaire (ACQ) and the Sinonasal Outcomes Test (SNOT-22).

    Measured: Change from baseline at 52 weeks

  6. Utilization of Rescue Medications

    Reduction in the use of rescue medications for acute exacerbations of chronic rhinosinusitis (CRS) following sinus surgery.

    Measured: Change from baseline at 52 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jun 2024
  2. Study start17 Jul 2024
  3. Primary completion17 Jul 2024
  4. Study completion17 Jul 2024

Why it stopped: Closed by sponsor, lack of enrollment.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06461949
Sponsor's protocol ID
10001856
Other IDs
001856-DC
Status last verified
Jul 2024
First submitted
8 Jun 2024
Last updated
25 Jul 2024
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: .Research Data for Statistical Analysis and Scientific Reporting will be shared. All participant data will be de-identified. Participants will be identified only by a unique study identification number.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Dupilumab in people with Allergic Fungal Rhinosinusitis (AFRS) and Chronic Rhinosinusitis (CRS), run by National Institute on Deafness and Other Communication Disorders (NIDCD).

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 45 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 25 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy of Dupilumab (time frame: Change from baseline at 52 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2024.

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