Recurrent Respiratory PapillomatosisPhase 1/2NCT04724980
Adjuvant PRGN-2012 in Adult Patients With Recurrent Respiratory Papillomatosis
A Phase 1/2 study testing PRGN-2012 - Phase I; Dose Level 1, PRGN-2012 - Phase I; Dose Level 2 and PRGN-2012 - Phase II; Dose Level 2 in people with Recurrent Respiratory Papillomatosis and Papillomavirus Infections, run by Precigen, Inc at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Respiratory Papillomatosis, Papillomavirus Infections, Papillomaviridae
- What is being tested?
- PRGN-2012 - Phase I; Dose Level 1, PRGN-2012 - Phase I; Dose Level 2 and PRGN-2012 - Phase II; Dose Level 2
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Mar 2021to 5 Jun 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
- 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 the 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 participant inappropriate for entry into this study. Participants 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 (> 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: A Phase 1/2 Study of Adjuvant PRGN-2012 in Adult Patients With Recurrent Respiratory Papillomatosis
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.
Read the 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.
- Being tested
- PRGN-2012 - Phase I; Dose Level 1, PRGN-2012 - Phase I; Dose Level 2, PRGN-2012 - Phase II; Dose Level 2
- Keywords
- Human Papilloma Virus, Dose escalation, laryngotracheal disease, papillomatous disease
- Medical subject headings
- Recurrent respiratory papillomatosis, Papillomavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PRGN-2012 - Phase I; Dose Level 1Drug
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.
PRGN-2012 - Phase I; Dose Level 2Drug
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.
PRGN-2012 - Phase II; Dose Level 2Drug
The Phase 2 portion is designed as a dose expansion study where patients are treated at the RP2D of 5 x 10^11 PU.
| Study group | Role | What they receive |
|---|---|---|
| Phase I; Dose Level 1 | Experimental | A standard dose escalation design was used to evaluate PRGN-2012 at a dose level of 1 × 10^11 Receives: Drug: PRGN-2012 - Phase I; Dose Level 1 |
| Phase I; Dose Level 2 | Experimental | A standard dose escalation design was used to evaluate PRGN-2012 at a dose level of 5 × 10^11 Receives: Drug: PRGN-2012 - Phase I; Dose Level 2 |
| Phase II; Dose Level 2 | Experimental | 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. Receives: Drug: PRGN-2012 - Phase II; Dose Level 2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 28 days
Secondary outcomes (10)
Safety of PRGN 2012 at RP2D
Systemic toxicity will be assessed through the capture of Treatment Emergent Adverse Events ( TEAEs) at Phase 1 and Phase 2 patients. The severity of the TEAEs will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 scale.
Measured: 1 year
Immune Responses
Change in HPV-specific T cells post-treatment compared to baseline
Measured: 1 year
Change in RRP Staging Assessment Scores Over Time
Absolute and percentage change from baseline in Derkay score over time following initiation of PRGN-2012 treatment
Measured: 1 year
Change in Vocal Function Scores over Time
Absolute and percentage change from baseline in VHI-10 score over time following initiation of PRGN-2012 treatment
Measured: 1 year
Time to recurrence of papillomatous disease after completion of treatment
Time to recurrence of papillomatous disease after completion of treatment will be recorded. Time from completion of treatment to first surgery will be assessed.
Measured: 1 year
Percentage of subjects with reduction in number of surgeries after completion of treatment
The number of surgeries in the 12 months post-treatment will be compared to the number of surgeries in the 12 months pre-treatment to identify subjects that have a reduction in the number of surgeries.
Measured: 1 year
Number of surgery during the 12 months pre and 12 months post treatment
The number of surgeries in the 12 months post-treatment will be compared to the number of surgeries in the 12 months pre-treatment.
Measured: 1 year
Overall Response Rate
Determine the percentage of subjects with at least a 50% decrease in the number of surgeries during the 12 month period following completion of PRGN-2012 treatment as compared to the number of surgeries during the 12 months prior to PRGN-2012 treatment initiation.
Measured: 1 year
Rate of pulmonary RRP partial response in participants with pulmonary disease
The fraction of participants with a pulmonary RRP partial response will be reported in all treated pulmonary participants.
Measured: 1 year
Rate of pulmonary RRP complete response in participants with pulmonary disease
The fraction of participants with a pulmonary RRP complete response will be reported in all treated pulmonary participants.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2021
- Study start16 Mar 2021
- Primary completion5 Jun 2024
- Study completion5 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Recurrent Respiratory PapillomatosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Arm1: Dose level 1: 1x10\^11 (Phase I) Arm2: Dose level 2: 5x10\^11 (Phase I) Amr3: Dose level 3: 5x10\^11 (Phase II)
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Precigen, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Amy Lankford, PhD, Study director, Precigen, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04724980
- Sponsor's protocol ID
- 210013
- Other IDs
- 21-C-0013
- Status last verified
- Jun 2025
- First submitted
- 23 Jan 2021
- Last updated
- 11 Jun 2025
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 39855244
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study of Adjuvant PRGN-2012 in Adult Patients With Recurrent Respiratory Papillomatosis
- ClinicalTrials.gov ID
- NCT04724980
- Acronym / sponsor ID
- 210013
- Keywords
- Human Papilloma Virus, Dose escalation, laryngotracheal disease, papillomatous disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Precigen, IncIndustry (pharma, biotech, devices)
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 16 Mar 2021 (actual)
- Primary completion
- 5 Jun 2024 (actual)
- Study completion
- 5 Jun 2026 (estimated)
- First posted
- 26 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Arm1: Dose level 1: 1x10^11 (Phase I) Arm2: Dose level 2: 5x10^11 (Phase I) Amr3: Dose level 3: 5x10^11 (Phase II)
| Arm | Type | Receives |
|---|---|---|
| Phase I; Dose Level 1 | Experimental | Drug: PRGN-2012 - Phase I; Dose Level 1A standard dose escalation design was used to evaluate PRGN-2012 at a dose level of 1 × 10^11 |
| Phase I; Dose Level 2 | Experimental | Drug: PRGN-2012 - Phase I; Dose Level 2A standard dose escalation design was used to evaluate PRGN-2012 at a dose level of 5 × 10^11 |
| Phase II; Dose Level 2 | Experimental | Drug: PRGN-2012 - Phase II; Dose Level 2A 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Age 18 years and older
- Clinical diagnosis of RRP
- 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
Key exclusion criteria (10 listed)
- 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.
- 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 the 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 participant inappropriate for entry into this study. Participants 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 (> 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PRGN-2012 - Phase I; Dose Level 1In 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. | Drug | Phase I; Dose Level 1 |
| PRGN-2012 - Phase I; Dose Level 2In 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. | Drug | Phase I; Dose Level 2 |
| PRGN-2012 - Phase II; Dose Level 2The Phase 2 portion is designed as a dose expansion study where patients are treated at the RP2D of 5 x 10^11 PU. | Drug | Phase II; Dose Level 2 |
Primary outcome
Determine the percentage of subjects with a complete response following treatment with PRGN-2012
Time frame: 1 year
A complete response is defined as no requirement for surgical intervention in the 12 months after treatment
Determine the incidence of dose limiting toxicities to evaluate safety and identify RP2D of PRGN-2012
Time frame: 28 days
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.
10 secondary outcomes
Safety of PRGN 2012 at RP2D
Time frame: 1 year
Immune Responses
Time frame: 1 year
Change in RRP Staging Assessment Scores Over Time
Time frame: 1 year
Change in Vocal Function Scores over Time
Time frame: 1 year
Time to recurrence of papillomatous disease after completion of treatment
Time frame: 1 year
Percentage of subjects with reduction in number of surgeries after completion of treatment
Time frame: 1 year
Number of surgery during the 12 months pre and 12 months post treatment
Time frame: 1 year
Overall Response Rate
Time frame: 1 year
Rate of pulmonary RRP partial response in participants with pulmonary disease
Time frame: 1 year
Rate of pulmonary RRP complete response in participants with pulmonary disease
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2025.
- Background: PubMed 39855244Norberg 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amy Lankford, PhD study director
Precigen, Inc
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PRGN-2012 - Phase I; Dose Level 1, PRGN-2012 - Phase I; Dose Level 2 and PRGN-2012 - Phase II; Dose Level 2 in people with Recurrent Respiratory Papillomatosis and Papillomavirus Infections, run by Precigen, Inc at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 11 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the percentage of subjects with a complete response following treatment with PRGN-2012 (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04724980, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2025.