Study to Evaluate the Safety, Tolerability, and Efficacy of PEP-TISSEEL in Subjects With Chronic Radiation Ulcer

Official title

An Adaptive Two-Part, Phase 1/2, Multi-Center, Double-Blinded, Randomized, Controlled Study of the Safety and Efficacy of Topically Applied PEP-TISSEEL in Participants With Chronic Radiation Ulcer

Overview

The goal of this clinical trial is to learn if drug Purified Exosome Product (PEP™) and Fibrin Sealant (TISSEEL® VH SD Kit) (PEP-TISSEEL) works to treat chronic radiation ulcer in adults and compare it with comparator TISSEEL. It will also learn about the safety of drug PEP-TISSEEL.

Interventions

• Combination product PEP-TISSEEL
  Purified Exosome Product (PEP™) and Fibrin Sealant (TISSEEL® VH SD Kit) (Biologic) (PEP-TISSEEL)
• Drug TISSEEL Fibrin Sealant KIT
  Fibrin Sealant (TISSEEL® VH SD Kit)
• Combination product PEP-TISSEEL
  Purified Exosome Product (PEP™) and Fibrin Sealant (TISSEEL® VH SD Kit) (Biologic) (PEP-TISSEEL)
• Drug TISSEEL Fibrin Sealant KIT
  Fibrin Sealant (TISSEEL® VH SD Kit)

Primary outcome measures

• Part 1(Phse1): Incidence of Treatment-Emergent Adverse Events (TEAEs) and Incidence of withdrawals from the study due to TEAEs [Time frame: 20 week]
• Part 2 (Phase2): The proportion of participants with complete wound closure during the 20 weeks of the Treatment Phase [Time frame: 20 weeks]

Secondary outcome measures (4)

• Part 1(Phase1): The proportion of participants with complete wound closure during the 20 weeks of the Treatment Phase [Time frame: 20 weeks]
• Part 2(Phase2): Wound area change (%) during the 20 weeks of the Treatment Phase [Time frame: 20 weeks]
• Part 2(Phase2): Time to complete wound closure during the 20 weeks of the Treatment Phase [Time frame: 20 weeks]
• Part 2(Phase2):Incidence of Treatment-Emergent Adverse Events (TEAEs) [Time frame: 20 weeks]

Eligibility criteria

Inclusion criteria

Participants in both study parts are eligible to be included if all of the following criteria apply:

Age and Sex

• Males and females aged ≥ 18 years at the time of signing the informed consent. Informed Consent
• Signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Type of Participant and Disease Characteristics

• Status post-radiation treatment, with radiation-induced ulcer. This includes participants with moist desquamation as well as full epidermal necrosis and superficial dermal ulcerations (this wound would otherwise be allowed to heal by secondary intention).
• Index ulcer classified as Grade 1 to Grade 3 according to the NCI-CTCAE, Version 5.0
• Area of index ulcer must be between 1 and 15 cm2 at screening and at randomization/baseline.
• Have failed conservative treatments including attempts at washing and local wound care, and be seeking therapy
• The chronic radiation ulcers are limited to cutaneous (skin) ulcers and not impacting mucosal (oral, nose, etc.) tissue. Sex and Contraceptive/Barrier Requirements
• Must meet one of the following criteria:

a. Female participants of non-childbearing potential defined as : i. Postmenopausal for at least 1 year (participant verbal confirmation acceptable), or surgically sterilized (i.e., hysterectomy or bilateral oophorectomy more than 3 months prior to screening); or ii. Bilateral tubal ligation more than 6 months prior to screening; or iii. Must have a negative β-hCG blood pregnancy test at screening and not be breastfeeding prior to being administered with the IP b. Male participants of non-childbearing potential are defined as those vasectomized participants whose vasectomy was performed 6 months prior to screening or those diagnosed as sterile by a physician c. Females and males of childbearing potential who practice an acceptable method of contraception defined as the use of any form of hormonal contraceptive, a barrier method with spermicide, condoms, intrauterine device, or abstinence from sexual intercourse starting at least 60 days prior to screening and continuing at least 30 days following the last treatment. Female will undergo pregnancy tests and must have a negative β-hCG blood pregnancy test at screening visit and negative urine pregnancy test at baseline visit and must not be breastfeeding prior to being administered with the IP. Other Inclusion Criteria

• Participants must be deemed by Radiation Oncologist at or greater than 6 months status/post-treatment to be without evidence of local recurrence
• Ability to comply with the study protocol
• Participants must be willing to undergo all clinical investigation-related procedures and attend all required visits including all follow-up visits Exclusion Criteria

Participants in both study parts are excluded if any of the following criteria apply:

Medical Conditions

• Study wound exhibits clinical signs and symptoms of infection at the screening visit
• Any participant that has vascular compromise that is untreated as defined by as by defined abnormal invasive or non-invasive vascular studies
• The index ulcer is within 2 cm of any other ulcer
• The non-Cutaneous CRUs and ulcers impacting mucosal (oral, nose, etc.) tissue Liver Safety
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN) Prior/Concurrent Clinical Study Experience
• Use of investigational drugs or biologics within 28 days prior to screening
• Participation in another interventional clinical study in the past 30 days or concurrent participation in another interventional clinical study Diagnostic Assessments
• Hemoglobin A1c (HbA1c) > 8%
• Serum creatinine l > 2.5 mg/dL
• Absolute neutrophil count of <500 neutrophils per mm3 over the course of enrollment
• Positive test for HBV, HCV, HIV Other Exclusion Criteria
• Active tanning, including the use of tanning booths, during the course of the study
• Any participant who would be unable to safely monitor the infection status of the index ulcer at home and return for scheduled visits
• Any participant with a life expectancy ≤ 6 months
• Pregnancy, including a positive pregnancy test at screening, or lactation
• Likely inability to comply with the protocol or cooperate fully with the Investigator and study site personnel
• Known or suspected active abuse of alcohol, or non-prescription drugs
• Participants who are incarcerated for any reason

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Walter Reed National Military Medical Center — Bethesda

Identifiers

NCT: NCT06793748 · PRO-00180

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗