This open-label study evaluates safety, vector shedding, and retreatment efficacy of Zopapogene imadenovec (Zopa) in adults with recurrent respiratory papillomatosis (RRP). Two cohorts will be enrolled (n=30): Cohort 1 to assess the magnitude and duration of adenoviral vector shedding in urine, feces, skin, and nasal tissue; Cohort 2 to assess the complete response rate following retreatment.

Key Inclusion Criteria:

• Age 18 years and older.
• Clinical diagnosis of recurrent respiratory papillomatosis with histological confirmation of papilloma.
• Cohort 1: Treatment-naïve with respect to Zopa.
• Cohort 2: Received a minimum of four administrations of Zopa at 5 × 10^11 PU per injection and require clinically indicated debulking procedures.
• Presence of laryngotracheal papillomas accessible for endoscopic cleanout.
• ECOG performance status 0 or 1.
• Sexually active participants of reproductive potential must agree to use contraception during treatment and for 120 days for males and 6 months for females after last dose.
• Ability to understand and sign informed consent.

Key Exclusion Criteria:

• Conditions or therapies that increase risk or interfere with participation per investigator judgment.
• Systemic corticosteroids >10 mg prednisone equivalent or other immunosuppressive medications within 14 days prior to dosing.
• Other systemic RRP treatments or investigational agents within 30 days.
• History of heparin-induced thrombocytopenia or vaccine-induced thrombotic thrombocytopenia.
• Active uncontrolled HIV, hepatitis B, or hepatitis C infection.
• Pregnant or nursing women.
• Known allergy to any study drug component.