A Study to Investigate the Efficacy and Safety of Verekitug (UPB-101) in Participants With Chronic Rhinosinusitis With Nasal Polyps

Study Overview
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Brief Summary
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The primary purpose of this study is to assess the effect of verekitug (UPB-101) on the endoscopically determined size and extend of nasal polyps in participants with chronic rhinosinusitis with nasal polyps (CRSwNP) and to assess the safety and tolerability of verekitug (UPB-101) compared to placebo.

Detailed Description
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This is a multicenter, randomized, placebo controlled, parallel group study to assess the efficacy and safety of verekitug (UPB-101) administered subcutaneously (SC) in participants with CRSwNP on background therapy with stable dosage of intranasal corticosteroids (INCS). Approximately 70 participants will be randomized. Participants will receive verekitug (UPB-101) or placebo over a 24-week treatment period. In addition, this study consists of a 3 to 5-week Screening Period and a 4-week Follow-up Period.

Official Title
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A Phase 2, Randomized, Double-blind, Placebo-controlled, Multi-center Study to Assess the Efficacy and Safety of Verekitug (UPB-101) in Participants With Chronic Rhinosinusitis With Nasal Polyps on a Background of Nasal Corticosteroids (VIBRANT)

Conditions
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Chronic Rhinosinusitis With Nasal Polyps

Intervention / Treatment
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* Drug: Verekitug (UPB-101)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant has signed, dated and received a copy of the Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written informed consent form (ICF). Participant is aged 18 to 75 years of age (inclusive) at the time of signing the ICF. Participant has physician diagnosed CRSwNP for at least 6 months prior to Visit 1 that fulfills all of the following: Severity consistent with need for surgery as defined by an endoscopic bilateral NPS of at least 5 out of 8 and a minimum score of 2 in each nasal cavity at Visit 1 based on central reading, as well as reconfirmed at Visit 2 based on local reading. NCS greater than and equal to (>=) 2 at Visit 2. Ongoing symptoms of CRSwNP for at least 8 weeks prior to Visit 1 such as rhinorrhea and/or reduction in smell. Participant has at least one of the following: In the 24 months prior to Visit 1, had a documented exacerbation of nasal polyposis requiring treatment with systemic corticosteroid. A medical contraindication/intolerance to systemic corticosteroid. Had prior surgery for NP (cannot be within 6 months prior to Visit 1 Stable standard of care treatment for CRSwNP for at least 30 days prior to Visit 1. At Visit 2, at least 21 days of background mometasone furoate nasal spray (MFNS) (or equivalent) background therapy. >=70 percent (%) diary compliance for MFNS (or equivalent) in the 14 days prior to Visit 2. Agrees to follow the required contraceptive techniques/methods Female or male participant agrees not to donate eggs or sperm, respectively, for a period of 120 days after the last dose of the study drug intervention or at the Final Visit, whichever occurs last Exclusion Criteria: Has undergone any intranasal and/or sinus surgery (including polypectomy) within 6 months prior to Visit 1. Expected need, in the opinion of the investigator, for NP surgery within 12 weeks of Visit 2. Comorbid asthma having forced expiratory volume in 1 second (FEV1) 50% or less of predicted normal at Visit 1. Conditions making participants non-evaluable at Visit 1 for the primary endpoint such as sino-nasal or sinus surgery changing the lateral wall structure of the nose, antrochoanal polyps, nasal septal deviation occluding at least one nostril, acute sinusitis, upper respiratory infection, ongoing rhinitis medicamentosa, fungal rhinosinusitis, nasal cavity benign or malignant tumors. Concurrent participation in a clinical study or has been treated with an investigational drug within 28 days or 5 half-lives, whichever is longer, prior to Visit 1. Previous exposure to verekitug (UPB-101) or known allergy/sensitivity to any of its excipients. Biologic therapy or systemic immunosuppressant to treat inflammatory disease or autoimmune disease within 6 months or 5 half-lives before Visit 1, whichever is longer, with the exception of oral c corticosteroids. Any vaccination within the Screening Period and treatment with a live (attenuated) vaccine within 12 weeks before Visit 2. Abnormal medical history, physical finding or safety finding and any clinical laboratory test result outside of the reference ranges that in the opinion of the Investigator may obscure the study data or interfere with the participant's safety. Allergic granulomatous angiitis (Churg-Strauss syndrome), granulomatosis with polyangiitis (Wegener's granulomatosis), Young's syndrome, Kartagener's syndrome or other dyskinetic ciliar syndromes, concomitant cystic fibrosis. Participant with comorbid asthma that also has a history or evidence of a clinically significant pulmonary condition (other than asthma). History of chronic alcohol or substance use disorder within 12 months prior to Visit 1.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Verekitug (UPB-101)<br>Participants will be administered 0.5 milliliter (mL) of verekitug (UPB-101) formulated solution (containing 100 milligrams [mg] of verekitug [UPB-101]) subcutaneously, every 12 weeks for 24 weeks. | Drug: Verekitug (UPB-101)<br>* Verekitug (UPB-101) 0.5 mL of formulated solution (100 mg verekitug [UPB-101])<br>|
| Placebo Comparator: Matching placebo<br>Participants will be administered verekitug (UPB-101) matching placebo solution, subcutaneously, every 12 weeks for 24 weeks. | Drug: Placebo<br>* Verekitug (UPB-101) matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Nasal Polyp Score (NPS) at Week 24 | Bilateral endoscopic NPS is a physician-reported scoring system to estimate the extent or severity of nasal polyps (NPs) based on assessments by nasal endoscopy. Each nostril is scored on a categorical scale of 0 to 4. The total score is the sum of the right and left scores (0-8). A higher score means severe disease. | At Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Nasal Congestion Score (NCS) Evaluated by the Nasal Polyposis Symptom Diary (NPSD) at Week 24 | Nasal congestion will be reported by participants daily, recalling nasal congestion severity over the previous 24 hours as none, mild, moderate, or severe (scores of 0, 1, 2, or 3, respectively). A higher score means worse outcome. | At Week 24 | 
| Change From Baseline in Opacification of Sinuses Measured by Lund Mackay Score (LMK) at Week 24 | LMK score or sinus opacification score is a physician-reported quality staging system for evaluation of severity of NPs based on assessments of the sinuses by computer tomography. The LMK staging system assigns a value of 0, 1, or 2 to each of the following 5 sinuses: maxillary, anterior ethmoid, posterior ethmoid, frontal, and sphenoid where in 0=sinus is totally patent, 1=sinus is partially opacified, 2=sinus completely opacified; A higher score means severe disease. | At Week 24 | 
| Change From Baseline in Mean Difficulty With Sense of Smell (DSS) Evaluated by the NPSD at Week 24 | Loss of smell based on participant-reported assessment of symptom severity of DSS, recalled over the past 24 hours. For the assessment, participants will be asked to assess their DSS for the previous day on a 4-point verbal scale of 0=none to 3=severe and record it in the electronic Diary. Higher daily DSS score indicates greater severity. | At Week 24 | 
| Percentage of Participants Requiring Systemic Corticosteroids or NP Surgery | Percentage of participants requiring systemic corticosteroids or NP surgery will be recorded. | Up to Week 24 | 
| Time to NP Surgery and/or Time to Systemic Corticosteroids for NP up to Week 24 | Time to NP surgery and/or time to systemic corticosteroids for NP will be recorded. | Up to Week 24 | 
| Change From Baseline in NPSD - Total Symptom Score (TSS) at Week 24 | Participants will complete a NPSD each morning. Questions will be asked to report common symptoms of nasal polyposis and symptom impacts. Participants will report severity of each symptom and symptom impact at its worse using a 4-point rating scale (0=no symptoms; 1=mild symptoms; 2=moderate symptoms; 3=severe symptoms). Higher score indicates more severe symptoms. | At Week 24 | 
| Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | From Baseline up to Week 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nasal Polyps, Sinusitis, Paranasal Sinus Diseases, Nose Diseases, Respiratory Tract Diseases, Otorhinolaryngologic Diseases, CRSwNP, Nasal Corticosteroids, VIBRANT