This study is currently recruiting participants.
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.
INCLUSION CRITERIA:
-Age 18 years and older
-Male or female patients with clinical diagnosis of RRP
--Histological diagnosis of papilloma confirmed by pathology report from a CLIA-certified (or comparable) laboratory
--Cohort 1: Subjects must be treatment-naive, i.e. has not previously been treated with any dose of Zopapogene imadenovec (Zopa)
--Cohort 2: Subjects must have received a minimum of 4 administrations of Zopa at 5x1011 PU per SQ injection (commercial product or through a clinical trial including subjects initially enrolled to Cohort 1) and continue to require clinically indicated debulking procedures for the management of their disease.
---Subjects that discontinued Zopa treatment due to an adverse event or have an ongoing adverse event (> Grade 1) due to Zopa treatment are ineligible for this study.
-Presence of laryngotracheal papillomas accessible for endoscopic cleanout
-Clinical performance status of ECOG of 0-1.
-Sexually active subjects (men and women) of reproductive potential must agree to use two methods of contraception: at least one highly effective and one other effective method. This contraceptive requirement must be maintained during the entire treatment period and continue for a minimum of 120 days after the last administration of Zopa for male participants and 6 months for female participants. Highly effective methods are defined as: Intrauterine device (IUD), hormonal (birth control pills, injections, implants), tubal ligation and partner s vasectomy; other effective methods are defined as: latex condom, diaphragm and cervical cap.
-All subjects must have the ability to understand and willingness to sign a written informed consent
EXCLUSION CRITERIA:
-Subjects with a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
-Subjects with a condition requiring systemic treatment with either corticosteroids (>10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled, topical intranasal or intro-ocular steroids, and adrenal replacement doses <10mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
-Subjects who have received any other systemic RRP treatments including investigational agents within the past 30 days or 3 half-lives of the prior drug (s). A 30-day washout is required for systemic bevacizumab treatment.
-Persisting toxicity related to prior therapy of Grade >1 NCI-CTCAE v 5.0; however, alopecia, sensory neuropathy Grade . 2 or other Grade . 2 AEs not constituting a safety risk based on investigator's judgment are acceptable.
-History of heparin-induced thrombocytopenia (HIT) or history vaccine-induced immune thrombotic thrombocytopenia (VITT). Note: Subjects who have a history of acute thrombotic events are eligible but will require additional monitoring for thrombotic events.
-Active uncontrolled HIV infection. No HIV testing is required unless mandated by local health authority.
-Active uncontrolled hepatitis B (positive HBsAg test) or hepatitis C (positive HCV RTPCR) infection
Note: No testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
-Known alcohol or drug abuse.
-Subject, who in the opinion of the investigator, may not be able to comply with the of the study.
-History of allergy to any study drug component.
-Pregnant or nursing women are excluded from this study.