This study is NOT currently recruiting participants.
Recurrent respiratory papillomatosis (RRP) is a disease that causes growths (called papillomas) in the airways. These can appear in the larynx, trachea, and lung; they can be fatal. RRP is caused by human papillomaviruses (HPVs). PRGN-2012 is a vaccine that boosts immunity against HPVs. Researchers want to know if PRGN-2012 can limit the regrowth of papillomas after surgery.
To test PRGN-2012 in people with RRP.
People aged 18 and older with RRP.
This study will last 4 to 7 years.
Participants will be observed during the first year. They will receive routine care from their own doctor. The will take a survey every 3 months to see how RRP is affecting their voice.
Participants are expected to need at least 3 surgeries to reduce the size of their papillomas during the year. When surgery is needed, the doctor will send images of the airways to the researchers.
In the second year, on the day after their first surgery, participants will receive a shot of PRGN-2012 in the upper arm. They will have 3 more shots over the next 12 weeks. At each visit participants will provide blood; tissue; urine; stool samples; and skin and nasal swabs. They will have images taken of the inside of their airways.
After their last shot, participants will return for 4 more visits over 52 weeks. Previous tests will be repeated.
Some participants may have a second round of PRGN-2012 shots and follow-up visits.
After all study visits are done, participants will receive follow-up calls every 6 months for 2 years
INCLUSION CRITERIA
Inclusion Criteria For Enrollment
-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
--Presence of laryngotracheal papillomas accessible for endoscopic surgical cleanout
--A history of surgical removal of papillomas such that in the opinion of the study team a subject is likely to meet the eligibility criteria for treatment which requires 3 or more surgical debulking procedures during the 12 month observation interval.
-Willing to undergo endoscopic evaluation and operative interventions with biopsies in compliance with this protocol
--Subjects must be managed by a Treating Physician that agrees to collect, store and provide quality endoscopic images collected at the time of every clinically-indicated surgical debulking procedure conducted. If Primary Treating Physician is unable or unwilling to adhere to these guidelines, then the subject must be willing to obtain endoscopic images at a study site or other qualified provider.
-Sexually active subjects (men and women) of reproductive potential must agree to use two methods of contraception: one highly effective and one other effective method throughout vaccine treatment and for at least 120 days after vaccine treatment. 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.
-Seronegative for hepatitis B antigen. Positive hepatitis B tests can be further evaluated by confirmatory tests (Hep B DNA quant, HBV viral load), and if confirmatory tests are negative, the subject can be enrolled.
-Seronegative for hepatitis C antibody unless antigen negative. If hepatitis C antibody test is positive, then subjects must be tested for the presence of antigen by Hep C RNA quant, HCV viral load and be HCV RNA negative
-All subjects must have the ability to understand and willingness to sign a written informed consent
Inclusion Criteria For Study Treatment
After a subject has completed a minimum of 12 months observation, they can be eligible for initial treatment with PRGN-2012, if the following criteria are met:
-Subject has required at least 3 debulking procedures within a 12 month window. A clinically-indicated procedure includes office-based procedures as well as OR-based procedures. The clinically-indicated procedure on Day -1 is included in the number of pre-treatment surgeries*.
-The study team has obtained endoscopic images collected within 14 days prior to every debulking procedure performed during the 12 month observation period**.
-Subject remains eligible for the study and does not meet any exclusion criteria, including but not limited to use of prohibited medications and pregnancy
*The observation window can be extended by up to 2 additional months (14 months total) in order to allow patients to become eligible, i.e. require 3 debulking procedures within a 12 month interval. Study team must consult with the Sponsor and obtain approval for window extension.
**If a number of images are missing from the observation interval, subject may still be eligible for treatment if they have images corresponding to at least 3 debulking procedures. Study team must consult with the Sponsor and obtain approval.
EXCLUSION CRITERIA
-History of significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (>= New York Heart Association Classification Class II), or serious cardiac arrhythmia that cannot be managed with medication.
-Any severe acute or chronic medical or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior, liver disease, lung disease (with the exception of what is specified in inclusion criteria), or laboratory abnormalities that, in the opinion of the investigators, 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 and in the judgment of the investigator, would make the subject inappropriate for entry into this study. Subjects with mild to moderate asthma or chronic obstructive pulmonary disease (COPD) well controlled with oral or inhaled medications are permitted to enroll.
-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.
-Subject has previously been treated with PRGN-2012
-Subjects have received any other investigational agents within the past 30 days
-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.
-Known alcohol or drug abuse.
-Subject, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
-History of allergy to study drug components.
-Pregnant or nursing women are excluded from this study