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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03234465
Recruitment Status : Terminated (No efficacy could be demonstrated, sponsor decided to prematurely end the study.)
First Posted : July 31, 2017
Results First Posted : November 23, 2020
Last Update Posted : November 23, 2020
Information provided by (Responsible Party):
Oragenics, Inc.

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Oral Mucositis Biological: AG013 Other: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : July 18, 2017
Actual Primary Completion Date : March 31, 2020
Actual Study Completion Date : July 13, 2020

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. 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)

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

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 identifier (NCT number): NCT03234465

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Sponsors and Collaborators
Oragenics, Inc.
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Study Director: Alan Joslyn, Ph.D. Sponsor GmbH
  Study Documents (Full-Text)

Documents provided by Oragenics, Inc.:
Study Protocol  [PDF] February 12, 2019
Statistical Analysis Plan  [PDF] March 19, 2020

Publications of Results:
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Responsible Party: Oragenics, Inc. Identifier: NCT03234465    
Other Study ID Numbers: AG013-ODOM-201
First Posted: July 31, 2017    Key Record Dates
Results First Posted: November 23, 2020
Last Update Posted: November 23, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Gastrointestinal Diseases
Digestive System Diseases
Mouth Diseases
Stomatognathic Diseases