Dupilumab in Allergic Fungal Rhinosinusitis (AFRS)

JRCT ID: jRCT2041210031

Registered date:14/06/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Allergic fungal rhinosinusitis
• Date of first enrollment: 26/08/2021
• Target sample size: 62
• Countries of recruitment: Argentina,Japan,China,Japan,Israel,Japan,United States,Japan,Canada,Japan,India,Japan,Saudi Arabia,Japan,Turkey,Japan
• Study type: Interventional

Intervention(s)

Drug: Dupilumab (SAR231893)
Pharmaceutical form:Injection solution, Route of administration: Subcutaneous

Drug: Placebo
Pharmaceutical form:Injection solution, Route of administration: Subcutaneous

Outcome(s)

Primary Outcome

1. Change from baseline in sinus opacifications assessed by computerized tomography (CT) scans using the Lund Mackay (LMK) score at Week 52 [ Time Frame: Baseline to Week 52 ]
LMK total score is based on assessment of the CT scan findings for each sinus area. The extent of opacification is rated between 0 (normal) to 24 (total opacification).

Secondary Outcome

1. Change from baseline in sinus opacifications assessed by CT scans using the LMK score at Week 24 [ Time Frame: Baseline to Week 24 ]
LMK total score is based on assessment of the CT scan findings for each sinus area. The extent of opacification is rated between 0 (normal) to 24 (total opacification).

2. Proportion of patients who receive systemic corticosteroids (SCS) and/or undergo/plan to undergo surgery for AFRS during the planned study treatment period [ Time Frame: Baseline to Week 52 ]

3. Change from baseline in monthly average nasal congestion/obstruction score from the Nasal symptom Diary at Week 24 and Week 52 [ Time Frame: Baseline to Week 24 and Week 52 ]
The nasal congestion/obstruction scores are scored from 0 ('No symptoms') to 3 ('Severe symptoms')

4. Change from Baseline in the monthly average anterior/posterior rhinorrhea score from the Nasal Symptom Diary at Week 24 and Week 52 [ Time Frame: Baseline to Week 24 and Week 52 ]
The rhinorrhea scores are scored from 0 ('No symptoms') to 3 ('Severe symptoms').

5. Change from baseline in endoscopic NPS compared to placebo at Week 24 and Week 52 [ Time Frame: Baseline to Week 24 and Week 52 ]
The total nasal polyps score (NPS) is the sum of the right and left nostrils, ranging from 0 (no polyps) to 8 (large polyps causing complete obstruction).

6. Change from baseline in 22-item sino-nasal outcome test (SNOT-22) total score at Week 24 and Week 52 [ Time Frame: Baseline to Week 24 and Week 52 ]
SNOT-22 is a patient-reported outcome (PRO) questionnaire. Score ranges from 0 to 110 with higher score indicating greater rhinosinusitis related health burden.

7. Change from baseline in monthly average total symptom score (TSS) derived from the Nasal Symptom Diary at Week 24 and Week 52 [ Time Frame: Baseline to Week 24 and Week 52 ]
TSS ranges from 0 to 9. Higher scores on the TSS indicate greater symptom severity.

8. Change from baseline in visual analog scale (VAS) rhinosinusitis at Week 24 and Week 52 [ Time Frame: Baseline to Week 24 and Week 52 ]
VAS score ranges from 0 ('not troublesome') to 10 ('worst thinkable troublesome').

9. Change from baseline in University of Pennsylvania smell identification test (UPSIT) at Week 24 and Week 52 [ Time Frame: Baseline to Week 24 and Week 52 ]
The UPSIT score ranges from 0 to 40, with 40 being the best possible score.

10. Change from baseline in the score of decreased/loss of smell using the Nasal Symptom Diary at Week 24 and Week 52 [ Time Frame: Baseline to Week 24 and Week 52 ]
The decreased/loss of smell scores are scored from 0 ('No symptoms') to 3 ('Severe symptoms').

11. Change from baseline to Week 52 in three Dimensional CT volumetric measurement of the paranasal sinuses [ Time Frame: Baseline to Week 52 ]

12. Incidence of treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs) through Week 52 [ Time Frame: Baseline to Week 64 ]

13. Dupilumab concentration in serum over time [ Time Frame: Baseline to Week 52 ]

14. Percent change from baseline in total IgE in serum compared to placebo over the 52 weeks treatment period [ Time Frame: Baseline to Week 52 ]

15. Percent change from baseline in fungal-specific IgE in serum compared to placebo over the 52 weeks treatment period [ Time Frame: Baseline to Week 52 ]

16. Incidence of treatment-emergent anti-drug antibodies (ADA) to dupilumab over time [ Time Frame: Baseline to Week 64 ]

Key inclusion & exclusion criteria

• Age minimum: >= 6age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Participant must be at least 6 years of age (or the minimum legal age for adolescents in the country of the investigational site) at the time of signing the informed consent.
2) Participants with the diagnosis of AFRS adapted from criteria by Bent and Kuhn (meeting all):
- IgE mediated inflammatory response to fungal hyphae (specific IgE serology or skin test)
Evidence of sensitization to fungus by skin testing (at screening or documented historical positive skin test in the previous 12 months), or positive fungal-specific IgE in serum at screening.
- Nasal polyposis confirmed by nasal endoscopy at screening.
- Characteristic CT signs to be performed during screening period and can include any of the below signs as assessed by central reader:
* hyperdensities
* bony demineralization
* bone erosion of sinus
- Eosinophilic mucin/mucus identified within 5 years prior to screening or at screening with or without positive fungal stain.
3) AFRS patients with the following:
- An endoscopic Nasal Polyp Score (NPS) of at least 2 out of 4 for unilateral polyps or 3 out of 8 for bilateral polyps at Visit 1 (central reading) and Visit 2 (local reading) and,
- Sinus opacification in CT scan with an Lund Mackay (LMK) score of 9 for patients with unilateral polyps or 12 for patients with bilateral polyps during screening period and,
4) Body weight >=15 kg

Exclude criteria

Participants are excluded from the study if any of the following criteria apply:
- Patients with nasal conditions/concomitant nasal diseases making them non-evaluable at Visit 1 or for the primary efficacy.
- Nasal cavity malignant tumor and benign tumors.
- Known of fungal invasion into sinus tissue.
- Severe concomitant illness(es) that, in the investigator's judgment, would adversely affect the patient's participation in the study.
- Active tuberculosis or non-tuberculous mycobacterial infection, or a history of incompletely treated tuberculosis unless documented adequately treated.
- Diagnosed active endoparasitic infections; suspected or high risk of endoparasitic infection
- Known or suspected immunodeficiency
- Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 2 weeks before the Screening Visit 1 or during the screening period.
- History of systemic hypersensitivity or anaphylaxis to dupilumab or any of its excipients.
- Treatment with commercially available dupilumab within 12 months, participation in prior dupilumab clinical trial, or discontinued dupilumab use due to adverse event.
- Patients who are treated with intranasal corticosteroid drops; intranasal steroid emitting devices/stents; nasal spray using exhalation delivery system, such as Xhance, during screening period.
- Patients who are on intranasal corticosteroids (INCS) spray unless they have received stable dose for at least 4 weeks prior to Visit 1.
- Patients who have undergone sinus intranasal surgery (including polypectomy) within 6 months prior to Visit 1.
- Patients who have taken:
* Biologic therapy/systemic immunosuppressant to treat inflammatory disease or autoimmune disease within 5 half-lives prior to Visit 1
* Any investigational mAb within 5 half-lives prior to Visit 1
* Anti-IgE therapy (omalizumab) within 4 months prior to Visit 1.
- Treatment with a live (attenuated) vaccine within 4 weeks prior to Visit 1
- Leukotriene antagonists/modifiers unless patient is on a continuous treatment for at least 30 days prior to 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 screening or treatment period.
- Patients received SCS during screening period.
- Either intravenous immunoglobulin therapy and/or plasmapheresis within 30 days prior to Screening Visit (Visit 1).

Related Information

• Primary Sponsor: Tanaka Tomoyuki
• Secondary ID(s): NCT04684524,2020-002999-12