Study assessing the efficacy and safety of dupilumab in patients with Allergic Fungal Rhinosinusitis (AFRS)
Phase 3
Active, not recruiting
- Conditions
- Other allergic rhinitis,
- Registration Number
- CTRI/2022/05/042593
- Lead Sponsor
- Sanofi Healthcare India Private Limited
- Brief Summary
Thisis a Phase 3, multicenter, 52-week treatment, parallel-group, double-blind,randomized, placebo-controlled study to investigate the efficacy of dupilumab300 mg every 2 weeks (q2w) for adults and adolescents/children (≥6 to <12years) ≥60 kg, or dupilumab 200 mg q2w for adolescents/children ≥30 kg and<60 kg, and dupilumab 300 mg every 4 weeks (q4w) for adolescents/children≥15 kg and <30 kg with signs and symptoms of AFRS despite prior surgery.
Thestudy will primarily investigate the effect of dupilumab to reduce need forrepeated SCS and surgery. In addition, the study will also evaluate efficacy ofdupilumab to reduce disease burden in the sinuses (sinus opacification) byradiographic imaging, nasal polyps, clinical symptoms, and
exploreother measures of disease activity.
Theestimated duration is 4±1 weeks of screening and run-in period, followed by a3-year double blinded treatment period. There will be a post-treatmentfollow-up (FU) period up to 12 weeks
Approximately120 patients (60 per arm) with AFRS with prior history of surgery will be randomizedin a 1:1 ratio to receive either dupilumab or matching placebo. Randomizationwill be
stratified first byage (adults versus adolescents/children). In adults, randomization will be stratifiedfurther by time from last surgery (≤2 years, >2 years), disease pattern (unilateral/bilateralin the endoscopy at screening), and country. In adolescents/children, randomizationwill not be stratified further
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- All
- Target Recruitment
- 120
Inclusion Criteria
- Participant must be at least 6 years of age at the time of signing the informed consent.
- Participants with the diagnosis of AFRS adapted from criteria by Bent and Kuhn.
- AFRS patients with the following: An endoscopic 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 LMK score of 9 for patients with unilateral polyps or 12 for patients with bilateral polyps during screening period Prior sino-nasal surgery(ies) for AFRS Body weight ≥15 kg Male and/or female Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- o A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies Is not a woman of childbearing potential (WOCBP) Is a WOCBP and agrees to use an acceptable contraceptive method as described in Appendix 4 (Section 10.4) of the protocol during the study (at a minimum until 12 weeks after the last dose of study intervention).
- A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) on Day 1 before the first dose of study intervention.
- If a urine test on Day 1 cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required.
- In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
- Capable of giving signed informed consent as described in Appendix 1 (Section 10.1) of the protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
- In countries where legal age of majority is above 18 years, a specific ICF must also be signed by the participant’s legally authorized representative.
- For adolescents (≥12 to <18 years) and for children (≥6 to <12 years), both the adolescent/child and the parent/legally authorized representative must sign the specific ICF/assent form.
Exclusion Criteria
- Patients with conditions/concomitant diseases making them non-evaluable at Visit 1 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 within 2 weeks prior to Visit 1 (patient can be rescreened after resolution of symptoms).
- Ongoing rhinitis medicamentosa.
- Eosinophilic granulomatous polyangiitis (Churg-Strauss syndrome), granulomatosis with polyangiitis (Wegener’s granulomatosis), microscopic polyangiitis, Young’s syndrome, Kartagener’s syndrome or other dyskinetic ciliary syndromes, cystic fibrosis Patients with nasal cavity malignant tumor and benign tumors (eg, papilloma, hemangioma, etc) Known of fungal invasion into sinus tissue.
- Diagnosed with, suspected of, or at high risk of endoparasitic infection, and/or use of antiparasitic drug within 2 weeks before the Screening Visit (Visit 1) or during the screening period.
- Histories of human immunodeficiency virus (HIV) infection or positive HIV screen (antiHIV-1 and HIV-2 antibodies) serology at the Screening Visit (Visit 1).
- Severe concomitant illness(es) that, in the Investigator’s judgment, would adversely affect the patient’s participation in the study.
- Examples include, but are not limited to participants with short life expectancy, participants with uncontrolled diabetes (hemoglobin A1c ≥9%), participants with cardiovascular conditions (eg, Class III or IV cardiac failure according to the New York Heart Association classification), severe renal conditions (eg, participants on dialysis), hepato-biliary conditions (eg, Child-Pugh class B or C), neurological conditions (eg, demyelinating diseases), active major autoimmune diseases (eg, lupus, inflammatory bowel disease, rheumatoid arthritis, etc), other severe endocrinological, gastrointestinal, metabolic, pulmonary, or lymphatic diseases.
- The specific justification for participants excluded under this criterion will be noted in study documents (chart notes, electronic case report forms [eCRFs], etc).
- Known or suspected history of immunodeficiency, including history of invasive opportunistic infections (eg, tuberculosis [TB], histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, and aspergillosis), despite infection resolution, or otherwise recurrent infections of abnormal frequency or prolonged duration suggesting an immune-compromised status, as judged by the Investigator.
- Patients with active TB or 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 patient 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 would be performed on a country by country basis according to local guidelines if required by regulatory authorities or ethic boards.
- Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 2 weeks before the Screening Visit (Visit 1) or during the screening period.
- History of malignancy within 5 years before Visit 1, except completely treated in situ carcinoma of the cervix, completely treated and resolved nonmetastatic squamous or basal cell carcinoma of the skin.
- Known or suspected alcohol and/or drug abuse.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To evaluate the ability of dupilumab in reducing the need for rescue therapy in patients with AFRS 52 weeks Proportion of patients who receive SCS and/or undergo/plan to undergo surgery of AFRS during the planned study treatment period of 52weeks 52 weeks
- Secondary Outcome Measures
Name Time Method To evaluate the efficacy of treatment with dupilumab to reduce sinus opacification in a population with allergic
Trial Locations
- Locations (3)
All India Institute of Medical Sciences (AIIMS)
🇮🇳Jodhpur, RAJASTHAN, India
Batra Hospital & Medical Research Centre
🇮🇳Delhi, DELHI, India
Hindusthan Hospital
🇮🇳Coimbatore, TAMIL NADU, India
All India Institute of Medical Sciences (AIIMS)🇮🇳Jodhpur, RAJASTHAN, IndiaDr Kapil SoniPrincipal investigator8003898485ksoni805@gmail.com