Clinical trial NCT06164704: A Study to Investigate the Efficacy and Safety of Verekitug (UPB-101) in Participants with Chronic Rhinosinusitis with Nasal Polyps
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Chronic Rhinosinusitis with Nasal Polyps
Keywords: CRSwNP
Nasal Corticosteroids
VIBRANT
Nasal Polyps
Sinusitis
Paranasal Sinus Diseases
Nose Diseases
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Lead sponsor: Upstream Bio Inc.
Sponsor class: INDUSTRY
First posted: 2023-12-11
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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 85 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.
  * Average NCS greater than and equal to (\>=) 2 over 14 days before 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 (%) dosing 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. Participants with any clinically significant cardiac disease and/or ECG abnormality, in the opinion of the Investigator, obtained during the Screening Period should be excluded from the study.
* 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.

Primary outcomes:
measure: Change From Baseline in Nasal Polyp Score (NPS) at Week 24
timeFrame: At Week 24
Secondary outcomes:
measure: Change From Baseline in the Nasal Congestion Score (NCS) Evaluated by the Nasal Polyposis Symptom Diary (NPSD) at Week 24
timeFrame: At Week 24
measure: Change From Baseline in Opacification of Sinuses Measured by Lund Mackay Score (LMK) at Week 24
timeFrame: At Week 24
measure: Change From Baseline in Mean Difficulty With Sense of Smell (DSS) Evaluated by the NPSD at Week 24
timeFrame: At Week 24
measure: Percentage of Participants Requiring Systemic Corticosteroids or NP Surgery
timeFrame: Up to Week 24
measure: Time to First NP Surgery and/or Use of Systemic Corticosteroids for NP up to Week 24
timeFrame: Up to Week 24
measure: Change From Baseline in NPSD - Total Symptom Score (TSS) at Week 24
timeFrame: At Week 24
measure: Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: From Baseline up to Week 28
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Sensa Health LA (Sensa Health Clinical Research)
state: California
city: Newport Beach
country: United States
facility: NewportNativeMD, Inc.
state: California
city: Roseville
country: United States
facility: DaVinci, Research LLC
state: California
city: San Diego
country: United States
facility: Senta Clinic
state: California
city: Columbus
country: United States
facility: University of Missouri
state: Colorado
city: Wheat Ridge
country: United States
facility: Western States Clinical Research, Inc.
state: Colorado
city: Hollywood
country: United States
facility: Alfa Medical Research
state: Florida
city: Miami
country: United States
facility: Novaceut Clinical Research
state: Florida
city: Miami
country: United States
facility: Well Pharma Medical Research Corp.
state: Florida
city: Miami
country: United States
facility: IMIC Inc.
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Boise
country: United States
facility: Treasure Valley Medical Research
state: Idaho
city: Chicago
country: United States
facility: The University of Chicago
state: Illinois
city: Louisville
country: United States
facility: Advanced ENT and Allergy
state: Kentucky
city: White Marsh
country: United States
facility: Chesapeake Clinical Research, Inc.
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Great Neck
country: United States
facility: Northwell Health/Division of Allergy and Immunology
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Allergy, Asthma & Clinical Research Center
state: Oklahoma
city: Spartanburg
country: United States
facility: Spartanburg /Greer ENT & Allergy
state: South Carolina
city: Austin
country: United States
facility: Orion Clinical Research
state: Texas
city: Dallas
country: United States
facility: Alina Clinical Trials, LLC.
state: Texas
city: McKinney
country: United States
facility: Ears Nose and Throat Associates of Texas
state: Texas
city: San Antonio
country: United States
facility: Alamo Ent Associates
state: Texas
city: Norfolk
country: United States
facility: Eastern Virginia Medical School
state: Virginia
city: Bellingham
country: United States
facility: Bellingham Asthma, Allergy & Immunology Clinic
state: Washington
city: Greenfield
country: United States
facility: Allergy, Asthma and Sinus Center, S.C.
state: Wisconsin
city: Olomouc
country: Czechia
facility: NZZ MUDr Pavel Navratil
state: Czech Republic
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin
city: Muenster
country: Germany
facility: Universitaetsklinik Muenster, Klinik fur Hals-, Nasen- und Ohrenheilkunde
city: Tuebingen
country: Germany
facility: Universitätsklinik Tuebingen
city: Katowice
country: Poland
facility: Centrum Medyczne Angelius Provita
city: Kraków
country: Poland
facility: Centrum Medyczne "All-Med" Badania Kliniczne spolka komandytowa
city: Kraków
country: Poland
facility: Centrum Medyczne PROMED
city: Nadarzyn
country: Poland
facility: CENTRUM SŁUCHU I MOWY Sp. z o.o.
city: Strzelce Opolskie
country: Poland
facility: Centrum Medyczne Lucyna Andrzej Dymek s.c
city: Barcelona
country: Spain
facility: Centro Médico Teknon
city: Cadiz
country: Spain
facility: Hospital Universitario de Jerez de la Frontera
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz (UAM-FJD) Consultas Externas Isaac Peral
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
Study officials:
affiliation: Upstream Bio
name: Kiran Patel, MD
role: STUDY_DIRECTOR
References: