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Adjuvant PRGN-2012 in Adult Patients With Recurrent Respiratory Papillomatosis

Primary Purpose

Recurrent Respiratory Papillomatosis, Papillomavirus Infections, Papillomaviridae

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PRGN-2012
Sponsored by
Precigen, Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Respiratory Papillomatosis focused on measuring Human Papilloma Virus, Dose escalation, laryngotracheal disease, papillomatous disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • National Institutes of Health Clinical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Adjuvant PRGN-2012

Arm Description

Four PRGN-2012 administrations (on days 1, 15, 43, and 85) via subcutaneous injection.

Outcomes

Primary Outcome Measures

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
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.

Secondary Outcome Measures

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.
Immune Responses
Change in HPV-specific T cells post-treatment compared to baseline
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
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
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.
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.
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.
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.
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.
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.

Full Information

First Posted
January 23, 2021
Last Updated
October 3, 2023
Sponsor
Precigen, Inc
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04724980
Brief Title
Adjuvant PRGN-2012 in Adult Patients With Recurrent Respiratory Papillomatosis
Official Title
A Phase 1/2 Study of Adjuvant PRGN-2012 in Adult Patients With Recurrent Respiratory Papillomatosis
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 16, 2021 (Actual)
Primary Completion Date
June 2, 2024 (Anticipated)
Study Completion Date
June 2, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Precigen, Inc
Collaborators
National Cancer Institute (NCI)

4. Oversight

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

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Respiratory Papillomatosis, Papillomavirus Infections, Papillomaviridae
Keywords
Human Papilloma Virus, Dose escalation, laryngotracheal disease, papillomatous disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
38 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Adjuvant PRGN-2012
Arm Type
Experimental
Arm Description
Four PRGN-2012 administrations (on days 1, 15, 43, and 85) via subcutaneous injection.
Intervention Type
Drug
Intervention Name(s)
PRGN-2012
Intervention Description
In the Phase 1, 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 2 segment, PRGN-2012 is evaluated at the RP2D.
Primary Outcome Measure Information:
Title
Determine the percentage of subjects with a complete response following treatment with PRGN-2012
Description
A complete response is defined as no requirement for surgical intervention in the 12 months after treatment
Time Frame
1 year
Title
Determine the incidence of dose limiting toxicities to evaluate safety and identify RP2D of PRGN-2012
Description
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.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Safety of PRGN 2012 at RP2D
Description
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.
Time Frame
1 year
Title
Immune Responses
Description
Change in HPV-specific T cells post-treatment compared to baseline
Time Frame
1 year
Title
Change in RRP Staging Assessment Scores Over Time
Description
Absolute and percentage change from baseline in Derkay score over time following initiation of PRGN-2012 treatment
Time Frame
1 year
Title
Change in Vocal Function Scores over Time
Description
Absolute and percentage change from baseline in VHI-10 score over time following initiation of PRGN-2012 treatment
Time Frame
1 year
Title
Time to recurrence of papillomatous disease after completion of treatment
Description
Time to recurrence of papillomatous disease after completion of treatment will be recorded. Time from completion of treatment to first surgery will be assessed.
Time Frame
1 year
Title
Percentage of subjects with reduction in number of surgeries after completion of treatment
Description
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.
Time Frame
1 year
Title
Number of surgery during the 12 months pre and 12 months post treatment
Description
The number of surgeries in the 12 months post-treatment will be compared to the number of surgeries in the 12 months pre-treatment.
Time Frame
1 year
Title
Overall Response Rate
Description
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.
Time Frame
1 year
Title
Rate of pulmonary RRP partial response in participants with pulmonary disease
Description
The fraction of participants with a pulmonary RRP partial response will be reported in all treated pulmonary participants.
Time Frame
1 year
Title
Rate of pulmonary RRP complete response in participants with pulmonary disease
Description
The fraction of participants with a pulmonary RRP complete response will be reported in all treated pulmonary participants.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 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. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amy Lankford, PhD
Organizational Affiliation
Precigen, Inc
Official's Role
Study Director
Facility Information:
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Links:
URL
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2021-C-0013.html
Description
NIH Clinical Center Detailed Web Page

Learn more about this trial

Adjuvant PRGN-2012 in Adult Patients With Recurrent Respiratory Papillomatosis

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