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Trial record 13 of 25 for:    recurrent respiratory papillomatosis

Adjuvant PRGN-2012 in Adult Patients With Recurrent Respiratory Papillomatosis

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ClinicalTrials.gov Identifier: NCT04724980
Recruitment Status : Recruiting
First Posted : January 26, 2021
Last Update Posted : August 24, 2022
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Precigen, Inc ( PGEN Therapeutics, Inc., a subsidiary of Precigen, Inc. )

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).

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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 : October 20, 2022
Estimated Study Completion Date : October 20, 2023

Resource links provided by the National Library of Medicine


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.





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.



Information from the National Library of Medicine

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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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04724980


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

Locations
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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
PGEN Therapeutics, Inc., a subsidiary of Precigen, Inc.
National Cancer Institute (NCI)
Investigators
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Study Director: Amy Lankford, PhD Precigen, Inc
Additional Information:
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Responsible Party: PGEN Therapeutics, Inc., a subsidiary of Precigen, Inc.
ClinicalTrials.gov Identifier: NCT04724980    
Other Study ID Numbers: 210013
21-C-0013
First Posted: January 26, 2021    Key Record Dates
Last Update Posted: August 24, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Precigen, Inc ( PGEN Therapeutics, Inc., a subsidiary of Precigen, Inc. ):
Human Papilloma Virus
Dose escalation
laryngotracheal disease
papillomatous disease
Additional relevant MeSH terms:
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Respiratory Tract Infections
Recurrence
Respiratory Tract Diseases
Papillomavirus Infections
Papilloma
Disease Attributes
Pathologic Processes
DNA Virus Infections
Virus Diseases
Infections
Tumor Virus Infections
Neoplasms, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms