Efficacy, Safety and Tolerability of AG013 in Oral Mucositis Compared to Placebo When Administered Three Times Per Day

November 20, 2020 updated by: Oragenics, Inc.

A Phase 2, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Assess the Safety and Efficacy of Topically-applied AG013 for the Attenuation of Oral Mucositis in Subjects With Cancers of the Head and Neck Receiving Concomitant Chemoradiation Therapy

The purpose of the study is to evaluate the efficacy, safety and tolerability of topically administered AG013 compared to placebo for reducing Oral Mucositis (OM) in patients undergoing chemoradiation for the treatment of head and neck cancer, as measured by the duration, time to development, and overall incidence of OM during the active treatment phase, beginning from the start of chemoradiation therapy (CRT) until 2 weeks following its completion.

The effect of AG013 on patient-reported symptoms and analgesic use during the active treatment phase, and on the cumulative radiation dose administered before the onset of OM will also be evaluated, as will biomarkers and, in a subset of subjects, the PK (pharmacokinetic) profile of AG013.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a Phase 2, double-blind, placebo-controlled, 2-arm, multi-center trial in which subjects will be randomized in a 1:1 ratio to receive either placebo or AG013. AG013 is a mouth rinse formulation of Lactococcus lactis strain sAGX0085, deficient in the gene coding for thymidylate synthase and producing human TFF1 (Trefoil Factor 1).

Approximately 200 subjects will be enrolled in the study. To protect subjects from unanticipated safety risks, enrollment and treatment in the double-blind study will continue until 10 subjects on AG013 have been recruited. The Data Safety Monitoring Board (DSMB) will review safety data after these 10 subjects on AG013 have completed study treatment. If there are no safety signals identified, the study will continue to recruit the planned number of subjects.

There are 4 study periods as described below: screening, active treatment, short term follow-up and long term follow-up. The screening phase will be no longer than 4 weeks. The active treatment phase will be between 7 and 9 weeks depending on the subject's prescribed CRT (chemoradiation therapy) plan. The short term follow-up phase will be 4 weeks in duration. The long term follow-up will continue until 12 months post CRT. Oral mucositis (OM) assessments will begin at the start of CRT and continue until the subject has completed short term follow-up or until the OM resolves (as defined by a WHO (World Health Organization) score of ≤ 1), whichever comes first. Long term follow-up will continue for 12 months to assure that AG013 does not adversely impact the tumor response to anti-neoplastic therapy.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
200

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium, 1000
        • Jules Bordet Institute
      • Brussels, Belgium, 1090
        • University Hospital Brussels
      • Edegem, Belgium, 2650
        • University Hospital Antwerp
      • Leuven, Belgium, 3000
        • University Hospitals Leuven
      • Mechelen, Belgium, 2800
        • St. Maarten General Hospital
  • Germany
      • Aachen, Germany, 52074
        • University Hospital Aachen
      • Dachau, Germany, 85221
        • Amper Hospital
      • Freiburg, Germany, 79106
        • University Hospital Freiburg
      • Gießen, Germany, 35392
        • University Hospital Giessen and Marburg
      • Kassel, Germany, 34125
        • Hospital Kassel
      • Kiel, Germany, 24105
        • University Hospital Schleswig-Holstein
      • Krefeld, Germany, 47805
        • Helios Hospital Krefeld
      • Mainz, Germany, 55131
        • University Hospital Johannes Gutenberg - University of Mainz
      • Mannheim, Germany, 68167
        • University Hospital Mannheim
      • Munich, Germany, 81377
        • Ludwig Maximilians University Hospital
      • Mönchengladbach, Germany, 41063
        • Clinics Maria Hilf - Hospital St. Franziskus
      • Regensburg, Germany, 93053
        • University Hospital Regensburg
      • Saarbrücken, Germany, 85221
        • Caritas Klinikum
  • United Kingdom
      • Glasgow, United Kingdom, G12 0YN
        • Beatson West of Scotland Cancer Center
      • London, United Kingdom, SE1 9RT
        • Guy'S Hospital
      • Manchester, United Kingdom, M20 4BX
        • The Christie NHS Foundation Trust
      • Truro, United Kingdom, TR1 3LJ
        • Royal Cornwall Hospital
    • Devon
      • Plymouth, Devon, United Kingdom, PL6 8DH
        • Derriford Hospital
  • United States
    • Connecticut
      • Farmington, Connecticut, United States, 06030
        • University of Connecticut Health Center
    • Delaware
      • Newark, Delaware, United States, 19713
        • Helen F. Graham Cancer Center
    • Florida
      • Orlando, Florida, United States, 32806
        • UF Health Cancer Center
    • Georgia
      • Columbus, Georgia, United States, 31904
        • Columbus Regional Research Institute
    • Illinois
      • Decatur, Illinois, United States, 62526
        • Decatur Memorial Hospital
    • Indiana
      • Anderson, Indiana, United States, 46016
        • St. Vincent Anderson Regional, Cancer Center
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Norton Cancer Institute, Multicisciplinary Clinic
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Clinic Foundation
      • Shreveport, Louisiana, United States, 71103
        • Willis-Knighton Cancer Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-5008
        • University of Michigan
    • Nevada
      • Henderson, Nevada, United States, 89052
        • Comprehensive Cancer Centers of Nevada-Henderson
      • Reno, Nevada, United States, 89502
        • Renown Regional Medical Center
    • New York
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center, Albert Einstein College of Medicine, Department of Radiation Oncology
      • Lake Success, New York, United States, 11042
        • Northwell Health Cancer Institute / Center for Novel Cancer Therapeutics
      • Rochester, New York, United States, 14642
        • University of Rochester Medical Center
    • North Carolina
      • Gastonia, North Carolina, United States, 28054
        • CaroMont Regional Medical Center
      • Greenville, North Carolina, United States, 27834-4354
        • East Carolina Univ School of Dental Medicine
    • Ohio
      • Canton, Ohio, United States, 44708
        • Mercy Medical Center
      • Columbus, Ohio, United States, 43210
        • Ohio State University Comprehensive Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19140
        • Temple University Hospital, Radiation Oncology
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC Shadyside Hospital
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Hospital
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • Radiation Oncology Moser
    • Washington
      • Bellingham, Washington, United States, 98225
        • PeaceHealth St. Joseph Medical Center
      • Gig Harbor, Washington, United States, 98405
        • Multicare Health Center
      • Spokane, Washington, United States, 99216
        • Cancer Care NW

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Willing and able to understand and sign the study specific Informed Consent Form
  2. Pathologically-confirmed squamous cell carcinoma of the oral cavity, oropharynx, nasopharynx or hypopharynx or HPV-positive unknown primaries presumed to be of oropharyngeal, nasopharyngeal or hypopharyngeal origin
  3. Tumor HPV status established
  4. Planned to receive either primary or post-operative CRT
  5. Planned IMRT (Intensity-Modulated Radiotherapy)
  6. Planned administration of cisplatin administered weekly or tri-weekly during RT
  7. Males or females 21 years or older
  8. Karnofsky performance score (KPS) ≥ 70%

  9. Screening laboratory assessments:

    • Hemoglobin ≥ 10g/dl
    • White blood count ≥ 3500 cells/mm3
    • Absolute neutrophil counts ≥ 1500 cells/ mm3
    • Serum AST (aspartate aminotransferase) and ALT (alanine aminotransferase) ≤ 3 x ULN
    • Calculated Creatinine Clearance ≥ 50 ml/min
    • Negative pregnancy test (serum or urine) for females of childbearing potential performed 7 days before IMP (Investigational Medicinal Product) administration.
  10. Subjects of childbearing potential must confirm to use an effective method of birth control during study participation and for 30 days following the last treatment with IMP. Male subjects, when having hetero-sexual intercourse with a female of childbearing potential must use a condom during study participation and 90 days following the last treatment with IMP and their partner should use an effective method of birth control during that period as well.

Exclusion Criteria:

  1. Prior radiation to the head and neck
  2. Increased risk of developing infectious endocarditis
  3. Prior gene therapy
  4. Presence of active infectious oral disease
  5. Presence of any oral lesions that may confound the ability to assess oral mucositis grade
  6. Current use of antibiotic rinses or troches
  7. Herbal, alternative remedies, and alcohol containing over-the-counter mouthwashes are excluded during the course of the study
  8. Current alcohol abuse syndrome
  9. Chronic immunosuppression
  10. Known seropositive for HIV
  11. Use of investigational agent within 30 days of signing informed consent
  12. Tooth extraction prior to radiation in which the extraction site is not epithelialized
  13. Signs and symptoms of active dental disease
  14. Female subjects who are pregnant or nursing
  15. Known allergy to excipients of the IMP
  16. Inability to give informed consent or comply with study requirements
  17. Unwilling or unable to complete subject diary
  18. Any other clinical condition, psychiatric condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable or to comply with follow-up visits

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: AG013: three mouth rinses/day
Subjects will rinse three times per day with AG013 mouth rinse beginning from the start of radiotherapy until 2 weeks following its completion. The active treatment phase lasts for 7 to 9 weeks, depending on the duration of radiotherapy.
Biological: AG013
AG013 is made up of genetically modified (GM) bacteria called Lactococcus lactis (L. lactis). Wild type L. lactis are commonly used to produce dairy products including cheeses and milk. To make AG013, the DNA of L. lactis has been changed in the laboratory to secrete a protein called human Trefoil Factor 1 (hTFF1). hTFF1 is normally secreted in saliva and intestines. Trefoil factors have been shown to be important in protecting and healing mucosal tissues, such as the tissue in the mouth, when these tissues are damaged by cancer therapies such as chemotherapy and radiation therapy.
Placebo Comparator: Placebo: three mouth rinses/day
Subjects will rinse three times per day with placebo mouth rinse beginning from the start of radiotherapy until 2 weeks following its completion. The active treatment phase lasts for 7 to 9 weeks, depending on the duration of radiotherapy.
Other: Placebo
Subjects assigned to the placebo group will receive appearance- and taste-matched placebo powder.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Efficacy of AG013 Compared to Placebo for Reducing OM as Measured by Duration (in Days) of Severe Oral Mucositis (WHO Grades 3 or 4)
Time Frame: From the start of radiation therapy (RT) until 2 weeks following its completion, 7 to 9 weeks depending on the duration of CRT.
Duration (in Days) of Severe Oral Mucositis (WHO Grades 3 or 4)
From the start of radiation therapy (RT) until 2 weeks following its completion, 7 to 9 weeks depending on the duration of CRT.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Oragenics, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Alan Joslyn, Ph.D., Sponsor GmbH

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 18, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 31, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 13, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 21, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 28, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 31, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 23, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 20, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AG013-ODOM-201

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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