PRGN-2012 for Respiratory Papillomatosis

Overseen By Amy Lankford, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: PGEN Therapeutics, Inc., a subsidiary of Precigen, Inc.

Must not be taking: Corticosteroids, Immunosuppressants, others

Disqualifiers: Cardiovascular disease, Liver disease, Lung disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called PRGN-2012 (zopapogene imadenovec) for Recurrent Respiratory Papillomatosis (RRP), a rare disease caused by the human papillomavirus (HPV) that often requires frequent surgeries. The trial aims to determine the safety and effectiveness of different doses of PRGN-2012 in managing RRP. Ideal participants have undergone three or more surgical treatments for RRP in the last year and are willing to undergo endoscopic evaluations. This study offers hope for reducing the need for repeated surgeries in those with RRP. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that you stop any systemic therapy for RRP for at least 3 half-lives of the prior drug(s), and a 30-day washout period is needed for systemic bevacizumab treatment. If you are on corticosteroids or other immunosuppressive medications, you must stop them 14 days before the study drug administration, unless they are low-dose or specific types like inhaled or topical steroids.

Is there any evidence suggesting that PRGN-2012 is likely to be safe for humans?

Research shows that PRGN-2012, the treatment under study for Recurrent Respiratory Papillomatosis (RRP), has generally been well-tolerated in earlier studies. In one study involving 38 adults with RRP, researchers administered the treatment and closely monitored their safety. Some patients experienced side effects, but these were manageable and did not raise major safety concerns. Importantly, the FDA has fully approved PRGN-2012 for another use, suggesting confidence in its safety for humans. This is encouraging for those considering participation in a clinical trial with this treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for respiratory papillomatosis?

Unlike the standard treatments for respiratory papillomatosis, which typically involve surgical removal of the growths or antiviral therapies, PRGN-2012 offers a novel approach by utilizing a targeted immunotherapy. This experimental treatment is unique because it harnesses the body's immune system to specifically target and eliminate the virus responsible for the condition, potentially reducing the need for repeated surgeries. Researchers are excited about PRGN-2012 because it not only aims to control the growths more effectively but also promises a longer-lasting solution by addressing the root cause of the disease rather than just its symptoms.

What evidence suggests that PRGN-2012 might be an effective treatment for Respiratory Papillomatosis?

Research has shown that PRGN-2012 holds promise for treating Recurrent Respiratory Papillomatosis (RRP). In studies, 83% of patients experienced a complete response, significantly improving their symptoms. This trial will assess PRGN-2012 at various dose levels to determine its safety and efficacy. The treatment targets the human papillomavirus (HPV), which causes RRP, through a gene therapy method. Evidence suggests that PRGN-2012 can reduce the need for repeated surgeries in individuals with this condition. These findings offer hope for those seeking new ways to manage RRP effectively. ^{4 5 6 7 8}

Who Is on the Research Team?

Amy Lankford, PhD

Principal Investigator

Precigen, Inc

Are You a Good Fit for This Trial?

Adults over 18 with Recurrent Respiratory Papillomatosis (RRP), a condition linked to HPV causing growths in the airways, are eligible. They must have had multiple treatments for RRP in the past year and be able to consent. Participants need proper organ function, not be on certain drugs or immunosuppressants, and agree to use two contraception methods if applicable.

Inclusion Criteria

I have growths in my throat or windpipe, with or without lung involvement.

I agree to use two forms of birth control during and for 4 months after vaccine treatment.

All participants must have the ability to understand and willingness to sign a written informed consent

Exclusion Criteria

I've had surgery to remove skin growths and can't safely wait six weeks between treatments.

Participants who are receiving any other investigational agents

History of allergy to study drug components

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Safety and tolerability of PRGN-2012 assessed at two different dose levels

4 weeks

4 visits (in-person) on days 1, 15, 43, and 85

Phase 2 Treatment

Treatment with PRGN-2012 at the recommended Phase 2 dose to determine safety and efficacy

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• PRGN-2012

Trial Overview The trial is testing PRGN-2012 as an additional treatment for adults with RRP who often require surgery. It's designed to see if this drug can reduce the disease burden. The study includes endoscopic evaluations and biopsies following protocol guidelines.

How Is the Trial Designed?

Group I: Phase II; Dose Level 2 Experimental Treatment 1 Intervention

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 II: Phase I; Dose Level 2 Experimental Treatment 1 Intervention

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

Group III: Phase I; Dose Level 1 Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

PGEN Therapeutics, Inc., a subsidiary of Precigen, Inc.

Lead Sponsor

Trials

3

Recruited

200+

Precigen, Inc

Lead Sponsor

Trials

7

Recruited

300+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Recurrent respiratory papillomatosis, caused by human papillomavirus (HPV), can lead to severe airway obstruction and respiratory distress, as demonstrated in a case of a pregnant patient who required an emergency tracheostomy.

The condition may worsen during pregnancy, suggesting that hormonal changes could influence the growth of HPV-induced lesions, highlighting the need for careful management in affected individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent respiratory papillomatosis in pregnancy: a case of emergent airway management. Scurry, WC., McGinn, JD.[2009]

HPV vaccination, specifically with the Gardasil® quadrivalent vaccine, significantly reduced the number of surgical procedures needed per year for patients with recurrent respiratory papillomatosis (RRP), with an average decrease of 4.43 procedures after vaccination.

The vaccination also increased the intersurgical interval (ISI) by an average of 15.73 months, suggesting that it may effectively prolong the time between surgeries for RRP patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy of Human Papillomavirus Vaccination as an Adjuvant Therapy in Recurrent Respiratory Papillomatosis. Ponduri, A., Azmy, MC., Axler, E., et al.[2023]

In a first-in-human phase 1 study involving adult patients with severe recurrent respiratory papillomatosis (RRP), the immune-therapeutic PRGN-2012 showed a promising 50% complete response rate at the highest dose, indicating its potential efficacy in enhancing HPV-specific T cell immunity.

The study found that responders to PRGN-2012 had a distinct immune profile, including greater expansion of HPV-specific T cells and lower papilloma HPV gene expression, suggesting that these factors may influence the effectiveness of the treatment and the tumor microenvironment's response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The tumor microenvironment state associates with response to HPV therapeutic vaccination in patients with respiratory papillomatosis. Norberg, SM., Bai, K., Sievers, C., et al.[2023]

In a study of 42 patients with recurrent respiratory papillomatosis (RRP) treated with alfa-IFN, those with HPV type 11 showed insufficient response to therapy, highlighting the need for reevaluation of treatment strategies.

Five patients experienced malignant transformation in the lungs or nasopharynx, particularly among smokers, indicating a significant risk associated with long-term RRP and HPV type 11 infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence, age at onset, and potential reasons of malignant transformation in recurrent respiratory papillomatosis patients: 20 years experience. Gerein, V., Rastorguev, E., Gerein, J., et al.[2022]

In a study of 112 patients with recurrent respiratory papillomatosis (RRP), various surgical treatments (KTP, CO2, and microdebrider) showed similar effectiveness in improving the Derkay anatomical score, indicating that the choice of surgical method does not significantly impact outcomes.

Both adult and pediatric patients experienced reduced disease burden when treated with bevacizumab or cidofovir, with adult patients showing a higher prevalence of dysplasia compared to pediatric patients, suggesting a need for careful monitoring in adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgery and Adjuvant Therapy Improve Derkay Scores in Adult and Pediatric Respiratory Papillomatosis. Hock, K., Kennedy, A., Howell, R., et al.[2022]

Recurrent respiratory papillomatosis, caused by human papillomavirus (HPV), leads to wart-like growths in the aerodigestive tract, primarily affecting children around 5 years old and adults in their 30s.

Surgical resection is the primary treatment to ensure airway safety, but patients typically need multiple surgeries due to the recurring nature of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent respiratory papillomatosis. Murray, LN., Miller, RH.[2006]

In a study of 51 patients with adult-onset recurrent respiratory papillomatosis (AORRP), a remission rate of 69% was observed, indicating that most patients can achieve remission after intensive treatment.

Interestingly, the use of adjuvant intralesional cidofovir was associated with a lower likelihood of remission, as 87% of patients not in remission had received this treatment, suggesting it may negatively impact treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment results in adult-onset recurrent respiratory papillomatosis. Verguts, MM., Genbrugge, E., de Jong, FI.[2018]

In a study of 57 Danish children with juvenile-onset recurrent respiratory papillomatosis (RP) followed for an average of 14 years, younger children (under 5 years) required significantly more surgeries in the first year, averaging 4.1 procedures, indicating a more aggressive disease course in this age group.

The overall rate of surgeries decreased over time, particularly for older children and those without a maternal history of condylomas, but about one-third of patients still experienced constant or increasing surgical needs, highlighting the variability in disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical course of recurrent respiratory papillomatosis in Danish children. Silverberg, MJ., Thorsen, P., Lindeberg, H., et al.[2022]

Citations

1. thelancet.com thelancet.com/journals/lanres/article/PIIS2213-2600(24)00368-0/abstract

PRGN-2012 gene therapy in adults with recurrent ... We aimed to assess the safety and clinical activity of PRGN-2012 in adult patients with RRP treated at the recommended phase 2 dose.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06538480

Confirmatory Study of PRGN-2012 in Patients With RRP Patients will be treated with PRGN-2012 and followed for at least 12 months to evaluate for efficacy and safety endpoints. Official Title. A Phase 3 Trial of ...

3. primetherapeutics.com primetherapeutics.com/high-cost-therapy-profile-june-2025

High-Cost Therapy Profile: June 2025 The following are clinical trials evaluating zopapogene imadenovec in RRP: NCT04724980: A Phase 1/2 Study of Adjuvant PRGN-2012 in Adult ...

4. investors.precigen.com investors.precigen.com/news-releases/news-release-details/fda-grants-priority-review-precigens-bla-prgn-2012-treatment

FDA Grants Priority Review to Precigen's BLA for PRGN ... PRGN-2012 would be the first and only available FDA-approved therapy for eligible patients with RRP, a rare and devastating chronic disease.

5. hcplive.com hcplive.com/view/long-term-data-support-new-zopapogene-imadenovec-approval-for-rrp

Long-Term Data Support New Zopapogene Imadenovec ... Zopapogene imadenovec demonstrates sustained complete responses in 83% of patients with recurrent respiratory papillomatosis over a median ...

6. fda.gov fda.gov/media/188264/download?attachment

Package Insert - PAPZIMEOS The safety data described in this section reflects exposure to PAPZIMEOS in one clinical study. (Study PRGN-2012-201). A total of 38 adults with recurrent ...

7. investors.precigen.com investors.precigen.com/news-releases/news-release-details/precigen-announces-full-fda-approval-papzimeos-zopapogene

Precigen Announces Full FDA Approval of PAPZIMEOS ... Precigen Announces Full FDA Approval of PAPZIMEOS (zopapogene imadenovec-drba), the First and Only Approved Therapy for the Treatment of Adults ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06538480

Confirmatory Study of PRGN-2012 in Patients With RRP Patients will be treated with PRGN-2012 and followed for at least 12 months to evaluate for efficacy and safety endpoints. Official Title. A Phase 3 Trial of ...