PRGN-2012 for Respiratory Papillomatosis

Not currently recruiting at 2 trial locations

Overseen By Amy Lankford, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Precigen, Inc

Must not be taking: Immunosuppressants, RRP treatments

Disqualifiers: Severe medical conditions, Pregnancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests PRGN-2012, a treatment for respiratory papillomatosis (RRP), a condition that causes growths in the airways and often requires surgery. The main goal is to evaluate how effectively PRGN-2012 reduces the need for surgical interventions in adults with RRP. Suitable candidates have a clinical diagnosis of RRP and require surgery for management. Participants must use contraception if sexually active and be willing to sign a consent form. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking any immunosuppressive medications and other treatments for RRP. If you are on these medications, you will need to discontinue them to participate in the study.

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

Research has shown that PRGN-2012, also known as PAPZIMEOS, was safe in earlier studies. In one study, 38 adults with recurrent respiratory papillomatosis (RRP) received PAPZIMEOS, and most participants tolerated the treatment well. Although some side effects occurred, they were mostly mild to moderate. Importantly, PAPZIMEOS has full FDA approval for use in adults. This approval indicates a strong safety record, as the FDA requires thorough safety checks before approving a treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

PRGN-2012 is unique because it uses a cutting-edge approach called "gene therapy" to tackle respiratory papillomatosis. Unlike traditional treatments that often rely on repetitive surgical procedures to remove papillomas, PRGN-2012 aims to address the root cause by modifying the patient's own cells to fight the virus responsible for the growths. Researchers are excited about this treatment because it has the potential to reduce the frequency of surgeries and provide a longer-lasting solution by enhancing the immune response against the virus.

What evidence suggests that PRGN-2012 might be an effective treatment for respiratory papillomatosis?

Studies have shown that PRGN-2012 looks promising for treating recurrent respiratory papillomatosis (RRP). Research indicates that 83% of patients experienced lasting improvements, with symptoms significantly reduced or eliminated. PRGN-2012 targets the virus causing RRP, aiming to halt its growth. This treatment could be a breakthrough as it might become the first FDA-approved therapy specifically for RRP. Ongoing studies, including this trial where all participants receive PRGN-2012, aim to confirm these positive results in more patients. ^{2 4 5 6 7}

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 RRP (a condition causing wart-like growths in the airways) needing surgery can join. They must be able to consent, use contraception if sexually active, and have a good performance status (able to carry out daily activities). Those with severe health issues or on certain medications for RRP or other investigational drugs within the last month cannot participate.

Inclusion Criteria

I agree to use birth control during the study.

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

I need surgery for my recurrent respiratory papillomatosis.

Exclusion Criteria

Severe acute or chronic medical or psychiatric conditions that 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 who had received any other investigational agents within the past 30 days

Pregnant women are excluded from this study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PRGN-2012 for the treatment of recurrent respiratory papillomatosis

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's effectiveness in treating adults with Respiratory Papillomatosis (RRP), which causes wart-like growths due to Human Papillomavirus. The study aims to confirm previous results showing benefits of this treatment.

How Is the Trial Designed?

Group I: All participants Experimental Treatment 1 Intervention

PRGN-2012 is already approved in United States, European Union for the following indications:

Approved in United States as PRGN-2012 for:

• Recurrent Respiratory Papillomatosis (RRP)

Approved in European Union as PRGN-2012 for:

• Recurrent Respiratory Papillomatosis (RRP)

Who Is Running the Clinical Trial?

Precigen, Inc

Lead Sponsor

Trials

7

Recruited

300+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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 ...