Adjuvant PRGN-2012 in Adult Patients With Recurrent Respiratory Papillomatosis

• ClinicalTrials.gov Identifier: NCT04724980
• Recruitment Status: Recruiting
• First Posted: January 26, 2021
• Last Update Posted: January 9, 2023
• Sponsor: Precigen, Inc
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Precigen, Inc

Study Description

Brief Summary:

This is a Phase I/II 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.

Condition or disease	Intervention/treatment	Phase
Recurrent Respiratory Papillomatosis; Papillomavirus Infections; Papillomaviridae	Drug: PRGN-2012	Phase 1; Phase 2

Detailed Description:

This is a nonrandomized, Phase I/II safety and tolerability study. The safety and tolerability of PRGN-2012 will be assessed following two different dose levels during the Phase I dose escalation trial. In the Phase II portion of the study, treatment with PRGN-2012 at recommended Phase 2 dose (RP2D) will be used to determine the percentage of patients who have an increase in their surgery-free interval (SFI).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 48 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Study of Adjuvant PRGN-2012 in Adult Patients With Recurrent Respiratory Papillomatosis
• Actual Study Start Date: March 16, 2021
• Estimated Primary Completion Date: March 20, 2024
• Estimated Study Completion Date: March 20, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Adjuvant PRGN-2012; Four PRGN-2012 administrations (on days 1, 15, 43, and 85) via subcutaneous injection.	Drug: PRGN-2012; In the Phase I, 3+3 dose escalation clinical trial evaluating PRGN-2012 at two dose levels (1x10^11 and 5x10^11 particle units (PU)) administered as adjuvant therapy prior to standard-of-care debulking surgery. In the Phase II segment, PRGN-2012 is evaluated at the RP2D.

Outcome Measures

Primary Outcome Measures :

1. Determine the percentage of patients with an increase in their surgery-free interval (SFI) following adjuvant treatment with PRGN-2012 [ Time Frame: 12 months ]
   Measuring the mean duration between successive clinically-indicated surgeries in the 12 months after treatment for that patient and determining whether that duration is longer than the mean duration between successive clinically-indicated surgeries in the 12 months prior to treatment. This fraction of patients who are classified as having a success will be reported along with a 95% confidence interval.
2. Determine the incidence of dose limiting toxicities to evaluate safety and identify recommended Phase II adjuvant dosing (RP2D) of PRGN-2012 [ Time Frame: 28 days ]
   The incidence of dose limiting toxicities experienced by patients at each dose level will be reported per dose level and maximum tolerated dose will be the RP2D. The grade as well as the type of toxicity will be tabulated per dose level to evaluate safety.

Secondary Outcome Measures :

1. Time to recurrence of papillomatous disease after completion of treatment will be recorded [ Time Frame: 1 year ]
   Time to recurrence of papillomatous disease after completion of treatment will be recorded. The frequency of surgery in the 12 months before or after treatment will be assessed across all treated patients for a statistically significant difference using Wilcoxon matched-pairs analysis.
2. Rate of pulmonary RRP partial response in participants with pulmonary disease [ Time Frame: 1 year ]
   The fraction of participants with a pulmonary RRP partial response and a pulmonary RRP complete response will be reported in all treated pulmonary participants, along with 95% confidence intervals for each.
3. Frequency of debulking surgery during the 12 months pre and 12 months post treatment [ Time Frame: 1 year ]
   The frequency of surgery in the 12 months before or after treatment will be assessed across all treated patients for a statistically significant difference using Wilcoxon matched-pairs analysis.
4. Rate of pulmonary RRP complete response in participants with pulmonary disease [ Time Frame: 1 year ]
   The fraction of participants with a pulmonary RRP partial response and a pulmonary RRP complete response will be reported in all treated pulmonary participants, along with 95% confidence intervals for each.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

INCLUSION CRITERIA:

• Age 18 years and older

• Clinical diagnosis of RRP

  • Histological diagnosis of papilloma confirmed by pathology report from a CLIA-certified laboratory
  • Presence of laryngotracheal papillomas with or without pulmonary RRP
  • A history of 2 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

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 surgical 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.
• 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.

Contacts and Locations

Contacts

Contact: Amy Lankford, PhD; 301-556-9900; clinicaltrials@precigen.com

Locations

United States, Maryland

National Institutes of Health Clinical Center; Recruiting

Bethesda, Maryland, United States, 20892

Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937

Sponsors and Collaborators

Precigen, Inc

National Cancer Institute (NCI)

Investigators

• Study Director: Amy Lankford, PhD; Precigen, Inc

More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

• Responsible Party: Precigen, Inc
• ClinicalTrials.gov Identifier: NCT04724980
• Other Study ID Numbers: 210013; 21-C-0013
• First Posted: January 26, 2021
• Last Update Posted: January 9, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Precigen, Inc:

Human Papilloma Virus; Dose escalation; laryngotracheal disease; papillomatous disease

Additional relevant MeSH terms:

Respiratory Tract Infections; Recurrence; Respiratory Tract Diseases; Papillomavirus Infections; Papilloma; Disease Attributes; Pathologic Processes; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Genital Diseases; Urogenital Diseases; Neoplasms, Squamous Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms