Adjuvant PRGN-2012 in Adult Patients With Recurrent Respiratory Papillomatosis
A Phase 1/2 Study of Adjuvant PRGN-2012 in Adult Patients With Recurrent Respiratory Papillomatosis
2 other identifiers
interventional
38
1 country
1
Brief Summary
This is a Phase 1/2 study in patients with a Recurrent Respiratory Papillomatosis (RRP) disease burden that requires repeated surgical procedures for management. RRP is a rare disease caused by the human papillomavirus (HPV). Participants with a pathologically confirmed diagnosis of papilloma and a clinical diagnosis of RRP will be screened for this protocol.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Mar 2021
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 23, 2021
CompletedFirst Posted
Study publicly available on registry
January 26, 2021
CompletedStudy Start
First participant enrolled
March 16, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 5, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
June 5, 2026
ExpectedJune 11, 2025
June 1, 2025
3.2 years
January 23, 2021
June 9, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Determine the percentage of subjects with a complete response following treatment with PRGN-2012
A complete response is defined as no requirement for surgical intervention in the 12 months after treatment
1 year
Determine the incidence of dose limiting toxicities to evaluate safety and identify RP2D of PRGN-2012
The incidence of dose limiting toxicities in Phase 1 will be reported per dose level. The dose level at which less than or equal to 1 out of 6 patients experience DLT will be identified as a RP2D.
28 days
Secondary Outcomes (10)
Safety of PRGN 2012 at RP2D
1 year
Immune Responses
1 year
Change in RRP Staging Assessment Scores Over Time
1 year
Change in Vocal Function Scores over Time
1 year
Time to recurrence of papillomatous disease after completion of treatment
1 year
- +5 more secondary outcomes
Study Arms (3)
Phase I; Dose Level 1
EXPERIMENTALA standard dose escalation design was used to evaluate PRGN-2012 at a dose level of 1 × 10\^11
Phase I; Dose Level 2
EXPERIMENTALA standard dose escalation design was used to evaluate PRGN-2012 at a dose level of 5 × 10\^11
Phase II; Dose Level 2
EXPERIMENTALA dose of 5 x 10\^11 PU was established as the RP2D, and the Phase 2 portion was implemented. The Phase 2 portion is designed as a dose expansion study, where patients were treated at the RP2D to evaluate the safety and efficacy of PRGN-2012.
Interventions
In Phase 1, dose level 1 of the clinical trial, PRGN-2012 is administered at 1 × 10\^11 particle units as adjuvant therapy prior to standard debulking surgery.
In Phase 1, dose level 2 of the clinical trial, PRGN-2012 is administered at 5 × 10\^11 particle units as adjuvant therapy prior to standard debulking surgery.
The Phase 2 portion is designed as a dose expansion study where patients are treated at the RP2D of 5 x 10\^11 PU.
Eligibility Criteria
You may qualify if:
- Age 18 years and older
- Clinical diagnosis of RRP
- Histological diagnosis of papilloma confirmed by pathology report from a CLIA-certified (or comparable) laboratory
- Presence of laryngotracheal papillomas with or without pulmonary RRP
- A history of 3 or more interventions in the last 12 months for control of RRP
- Clinical performance status of ECOG of 0-1
- Willing to undergo endoscopic evaluation and operative interventions with biopsies in compliance with this protocol
- No systemic therapy for RRP for at least 3 half-lives of the prior drug(s). A 30-day washout is required for systemic bevacizumab treatment
- Participants who have received prior immunotherapy for RRP are permitted
- Participants must have adequate organ and marrow function as defined below:
- 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 a 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 participant can be enrolled.
- Seronegative for hepatitis C antibody unless antigen negative. If the hepatitis C antibody test is positive, then participants must be tested for the presence of antigen by Hep C RNA quant, HCV viral load, and be HCV RNA negative
- All participants must have the ability to understand and willingness to sign a written informed consent
You may not qualify if:
- A history of surgical debridement of papillomas such that in the opinion of the study team a participant is unlikely to be able to safely have a six-week interval between clinically indicated interventions.
- 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 (greater than or equal to New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
- Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg 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 \<10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- Participants who are receiving any other investigational agents
- Persisting toxicity related to prior therapy of Grade \>1 NCI-CTCAE v 5.0; however, alopecia, sensory neuropathy Grade less than or equal to 2 or other Grade less than or equal to 2 AEs not constituting a safety risk based on investigator's judgment are acceptable.
- Known alcohol or drug abuse.
- Participant, 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 women are excluded from this study because PRGN-2012 is an agent with unknown potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with PRGN-2012, breastfeeding should be discontinued if the mother is treated with PRGN-2012. These potential risks may also apply to other agents used in this study.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Precigen, Inclead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Publications (1)
Norberg SM, Valdez J, Napier S, Kenyon M, Ferraro E, Wheatley M, Parsons-Wandell L, Doran SL, Lankford A, Sabzevari H, Brough DE, Schlom J, Gulley JL, Allen CT. PRGN-2012 gene therapy in adults with recurrent respiratory papillomatosis: a pivotal phase 1/2 clinical trial. Lancet Respir Med. 2025 Apr;13(4):318-326. doi: 10.1016/S2213-2600(24)00368-0. Epub 2025 Jan 21.
PMID: 39855244BACKGROUND
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Amy Lankford, PhD
Precigen, Inc
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 23, 2021
First Posted
January 26, 2021
Study Start
March 16, 2021
Primary Completion
June 5, 2024
Study Completion (Estimated)
June 5, 2026
Last Updated
June 11, 2025
Record last verified: 2025-06