Adjuvant PRGN-2012 in Adult Patients With Recurrent Respiratory Papillomatosis

NCT ID: NCT04724980

Last Updated: 2025-06-11

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-16
• Study Completion Date: 2026-06-05

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.

Detailed Description

This is a nonrandomized, Phase 1/2 safety and tolerability study. The safety and tolerability of PRGN-2012 will be assessed following two different dose levels during the Phase 1 dose escalation trial. In the Phase 2 portion of the study, treatment with PRGN-2012 at the recommended Phase 2 dose (RP2D) will be used to determine safety and efficacy of PRGN-2012.

Conditions

Recurrent Respiratory Papillomatosis; Papillomavirus Infections; Papillomaviridae

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase I; Dose Level 1

A standard dose escalation design was used to evaluate PRGN-2012 at a dose level of 1 × 10\^11

Group Type: EXPERIMENTAL

PRGN-2012 - Phase I; Dose Level 1

Intervention Type: DRUG

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.

Phase I; Dose Level 2

A standard dose escalation design was used to evaluate PRGN-2012 at a dose level of 5 × 10\^11

Group Type: EXPERIMENTAL

PRGN-2012 - Phase I; Dose Level 2

Intervention Type: DRUG

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.

Phase II; Dose Level 2

A 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.

Group Type: EXPERIMENTAL

PRGN-2012 - Phase II; Dose Level 2

Intervention Type: DRUG

The Phase 2 portion is designed as a dose expansion study where patients are treated at the RP2D of 5 x 10\^11 PU.

Interventions

PRGN-2012 - Phase I; Dose Level 1

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.

Intervention Type: DRUG

PRGN-2012 - Phase I; Dose Level 2

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.

Intervention Type: DRUG

PRGN-2012 - Phase II; Dose Level 2

The Phase 2 portion is designed as a dose expansion study where patients are treated at the RP2D of 5 x 10\^11 PU.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Precigen, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Amy Lankford, PhD

Role: STUDY_DIRECTOR

Precigen, Inc

Locations

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 39855244 (View on PubMed)

Related Links

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2021-C-0013.html

NIH Clinical Center Detailed Web Page

Other Identifiers

21-C-0013

Identifier Type: -

Identifier Source: secondary_id

210013

Identifier Type: -

Identifier Source: org_study_id