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

Phase 2

Terminated

Conditions: Oral Mucositis

Interventions: Biological: AG013
Other: Placebo

Registration Number: NCT03234465

Lead Sponsor: 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.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 200

Inclusion Criteria

Willing and able to understand and sign the study specific Informed Consent Form
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
Tumor HPV status established
Planned to receive either primary or post-operative CRT
Planned IMRT (Intensity-Modulated Radiotherapy)
Planned administration of cisplatin administered weekly or tri-weekly during RT
Males or females 21 years or older
Karnofsky performance score (KPS) ≥ 70%
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.
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

Prior radiation to the head and neck
Increased risk of developing infectious endocarditis
Prior gene therapy
Presence of active infectious oral disease
Presence of any oral lesions that may confound the ability to assess oral mucositis grade
Current use of antibiotic rinses or troches
Herbal, alternative remedies, and alcohol containing over-the-counter mouthwashes are excluded during the course of the study
Current alcohol abuse syndrome
Chronic immunosuppression
Known seropositive for HIV
Use of investigational agent within 30 days of signing informed consent
Tooth extraction prior to radiation in which the extraction site is not epithelialized
Signs and symptoms of active dental disease
Female subjects who are pregnant or nursing
Known allergy to excipients of the IMP
Inability to give informed consent or comply with study requirements
Unwilling or unable to complete subject diary
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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AG013: three mouth rinses/day	AG013	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.
Placebo: three mouth rinses/day	Placebo	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.

Primary Outcome Measures

Name	Time	Method
Efficacy of AG013 Compared to Placebo for Reducing OM as Measured by 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.	Duration (in Days) of Severe Oral Mucositis (WHO Grades 3 or 4)

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (50): University of Connecticut Health Center
🇺🇸
Farmington, Connecticut, United States
Comprehensive Cancer Centers of Nevada-Henderson
🇺🇸
Henderson, Nevada, United States
East Carolina Univ School of Dental Medicine
🇺🇸
Greenville, North Carolina, United States
University of Texas MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Huntsman Cancer Hospital
🇺🇸
Salt Lake City, Utah, United States
Amper Hospital
🇩🇪
Dachau, Germany
University Hospital Giessen and Marburg
🇩🇪
Gießen, Germany
University Hospital Johannes Gutenberg - University of Mainz
🇩🇪
Mainz, Germany
Ludwig Maximilians University Hospital
🇩🇪
Munich, Germany
Helen F. Graham Cancer Center
🇺🇸
Newark, Delaware, United States
Columbus Regional Research Institute
🇺🇸
Columbus, Georgia, United States
St. Vincent Anderson Regional, Cancer Center
🇺🇸
Anderson, Indiana, United States
Decatur Memorial Hospital
🇺🇸
Decatur, Illinois, United States
Willis-Knighton Cancer Center
🇺🇸
Shreveport, Louisiana, United States
Renown Regional Medical Center
🇺🇸
Reno, Nevada, United States
Northwell Health Cancer Institute / Center for Novel Cancer Therapeutics
🇺🇸
Lake Success, New York, United States
University of Rochester Medical Center
🇺🇸
Rochester, New York, United States
Ohio State University Comprehensive Cancer Center
🇺🇸
Columbus, Ohio, United States
Caromont Regional Medical Center
🇺🇸
Gastonia, North Carolina, United States
Temple University Hospital, Radiation Oncology
🇺🇸
Philadelphia, Pennsylvania, United States
Mercy Medical Center
🇺🇸
Canton, Ohio, United States
PeaceHealth St. Joseph Medical Center
🇺🇸
Bellingham, Washington, United States
Radiation Oncology Moser
🇺🇸
Charlottesville, Virginia, United States
Multicare Health Center
🇺🇸
Gig Harbor, Washington, United States
University Hospital Antwerp
🇧🇪
Edegem, Belgium
Jules Bordet Institute
🇧🇪
Brussels, Belgium
University Hospitals Leuven
🇧🇪
Leuven, Belgium
Cancer Care NW
🇺🇸
Spokane, Washington, United States
University Hospital Brussels
🇧🇪
Brussels, Belgium
St. Maarten General Hospital
🇧🇪
Mechelen, Belgium
University Hospital Aachen
🇩🇪
Aachen, Germany
University Hospital Freiburg
🇩🇪
Freiburg, Germany
Hospital Kassel
🇩🇪
Kassel, Germany
University Hospital Mannheim
🇩🇪
Mannheim, Germany
University Hospital Regensburg
🇩🇪
Regensburg, Germany
Clinics Maria Hilf - Hospital St. Franziskus
🇩🇪
Mönchengladbach, Germany
Caritas Klinikum
🇩🇪
Saarbrücken, Germany
Derriford Hospital
🇬🇧
Plymouth, Devon, United Kingdom
Beatson West of Scotland Cancer Center
🇬🇧
Glasgow, United Kingdom
The Christie NHS Foundation Trust
🇬🇧
Manchester, United Kingdom
Royal Cornwall Hospital
🇬🇧
Truro, United Kingdom
UPMC Shadyside Hospital
🇺🇸
Pittsburgh, Pennsylvania, United States
University Hospital Schleswig-Holstein
🇩🇪
Kiel, Germany
Helios Hospital Krefeld
🇩🇪
Krefeld, Germany
UF Health Cancer Center
🇺🇸
Orlando, Florida, United States
Norton Cancer Institute, Multicisciplinary Clinic
🇺🇸
Louisville, Kentucky, United States
Ochsner Clinic Foundation
🇺🇸
New Orleans, Louisiana, United States
University of Michigan
🇺🇸
Ann Arbor, Michigan, United States
Montefiore Medical Center, Albert Einstein College of Medicine, Department of Radiation Oncology
🇺🇸
Bronx, New York, United States
Guy's Hospital
🇬🇧
London, United Kingdom