TAVNEOS for Otolaryngologic Manifestations of Granulomatosis With Polyangiitis

NCT07176546 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2023-1580
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

This is a single center double-blind placebo-controlled study. Patients with GPA and active ears, nose, and throat (ENT) disease in at least two ENT domains, as defined after endoscopic visualization of the upper airway and audiometric evaluation, if applicable, by a single otolaryngologist using a validated GPA ENT disease activity score, will be eligible for inclusion. Patients will be treated with standard of care (SOC) treatment as determined by their treating rheumatologist. In addition to SOC, patients will be randomized to receive TAVNEOS 30mg BID or placebo. Patients will be followed for 52 weeks with standardized ENT assessment along with rheumatologic evaluation of overall disease activity with BVAS.

Conditions

Granulomatosis With Polyangiitis; Wegener's; GPA

Keywords

Tavneos; avacopan; GPA; ENT

Outcome Measures

Primary Outcomes (1)

• Proportion of patients in ENT remission without relapse

  The proportion of patients in ENT remission without relapse in each treatment group at week 52 with no glucocorticoid (GC) exposure 4 weeks prior to week 52, where ENT remission is defined as a score of 0 on GPA ENT disease activity score

  Week 52

Secondary Outcomes (12)

• Mean ENT disease activity score

  Week 52

• Change in ENT disease activity score

  Between week 26 and week 52

• Proportion of patients in ENT remission with BVAS 0 at week 52 and sustained remission

  Week 52

• Cumulative steroid dose

  Through study completion, an average of 60 weeks

• Duration of steroid-free remission

  Through study completion, an average of 60 weeks

Study Arms (2)

TAVNEOS

ACTIVE COMPARATOR

BID dose of 30 mg TAVNEOS

Drug: Avacopan

Placebo

PLACEBO COMPARATOR

BID dose of 30 mg TAVNEOS-matching placebo

Drug: Placebo

Interventions

Avacopan DRUG

BID dose of 30 mg TAVNEOS (3-10mg capsules)

Also known as: TAVNEOS

TAVNEOS

Placebo DRUG

BID dose of 30mg TAVNEOS-matching placebo (3-10mg capsules)

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• GPA diagnosis defined by score of ≥5 on 2022 ACR/EULAR Classification Criteria for GPA
• Active GPA (both newly diagnosed and relapsing disease) in the ENT domain within 1 month prior to screening, where the active disease is defined as a score of ≥2 on a GPA ENT disease activity score (7 items scored as 1= present 0= absent) performed by direct endoscopic visualization of the upper airway and audiometric evaluation, if applicable, by a single expert otolaryngologist. Items included in the GPA ENT disease activity score are:
• Bloody rhinorrhea (Daily blood stained nasal discharge)
• Objective stridor (Stridor assessed by doctor)
• Inflammation on nasal examination (Ulcers, granulation, friable mucosa on rigid nasal endoscopy. Excluding crusting)
• Inflammation on flexible laryngoscopy (Ulcers, granulation, friable mucosa in the larynx)
• Inflamed TM\*/middle ear (Persistent inflammation or granulation tissue in tympanic membrane/middle ear)
• Sudden sensorineural hearing loss (30db drop in 3 frequencies within 72 hours)
• Other ENT/upper airway manifestations of active GPA observed during structured ENT exam including but not limited to lacrimal gland dacryocystitis and endobronchial disease
• Age 18 and older
• Willing and able to comply with treatment and follow-up procedures
• Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months after completion of treatment.
• Willing and able to provide written informed consent
• Adequate liver function as defined by AST or ALT \<2x Upper Limit of Normal

You may not qualify if:

• Creatinine \>4.0mg/dl or GFR \<15 at baseline or dependence on dialysis
• Respiratory failure requiring mechanical ventilatory support or had experienced alveolar hemorrhage requiring invasive pulmonary ventilation support anticipated to last beyond the screening period of the study
• Previous treatment with TAVNEOS within 6 months of screening
• Inability to comply with study and/or follow-up procedures at investigator discretion.
• Intravenous glucocorticoids in the 4 weeks prior to screening except as premedication prior to infusion of rituximab
• Pregnant or breast-feeding
• Any other known multi-system autoimmune disease including eosinophilic granulomatosis with polyangiitis (Churg-Strauss), systemic lupus erythematosus, IgA vasculitis (Henoch-Schonlein), rheumatoid vasculitis, Sjogren's syndrome, anti-glomerular basement membrane disease, or cryoglobulinemic vasculitis
• Required dialysis or plasma exchange within 12 weeks prior to screening
• Have had a kidney transplant
• Any of the following within 12 weeks prior to screening: symptomatic congestive heart failure requiring prescription medication, unstable angina (unless successfully treated with stent or bypass surgery), clinically significant cardiac arrhythmia, myocardial infarction or stroke
• History or presence of any form of cancer within the 5 years prior to screening, with the exception of excised basal cell or squamous cell carcinoma of the skin, or carcinoma in situ such as cervical or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis
• Evidence of tuberculosis based on interferon gamma release assay (IGRA), tuberculin purified protein derivative (PPD) skin test, or chest radiography (X rays or CT scan) done at screening or within 6 weeks prior to screening
• HBV, HCV, or HIV viral screening test showing evidence of active or chronic viral infection done at screening or within 6 weeks prior to screening
• Received a live vaccine within 4 weeks prior to screening
• WBC count less than 3500/uL, or neutrophil count less than 1500/uL, or lymphocyte count less than 500/uL before start of dosing

Sponsors & Collaborators

• Robert Spiera, MD: lead
• Amgen: collaborator

Study Sites (2)

Hackensack Meridian School of Medicine - Advanced Lung and Airway Center

Edison, New Jersey, 08820, United States

Location

Hospital for Special Surgery

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Granulomatosis with Polyangiitis

Interventions

avacopan

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Robert F Spiera, MD

  Hospital for Special Surgery, New York

  PRINCIPAL INVESTIGATOR

• Lindsay Lally, MD

  Hospital for Special Surgery, New York

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Liza M Morales, MPH

CONTACT

212-774-2048; moralesli@hss.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 18, 2025
• First Posted: September 16, 2025
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): October 1, 2030
• Last Updated: September 19, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)