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

NCT03234465 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: AG013-ODOM-201
• Study Type: interventional
• Target: 200
• Locations: 4 countries
• Sites: 50

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.

Conditions

Oral Mucositis

Outcome Measures

Primary Outcomes (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)

  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.

Study Arms (2)

AG013: three mouth rinses/day

EXPERIMENTAL

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

Placebo: three mouth rinses/day

PLACEBO COMPARATOR

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

Interventions

AG013 BIOLOGICAL

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.

AG013: three mouth rinses/day

Placebo OTHER

Subjects assigned to the placebo group will receive appearance- and taste-matched placebo powder.

Placebo: three mouth rinses/day

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Oragenics, Inc.: lead

Study Sites (50)

University of Connecticut Health Center

Farmington, Connecticut, 06030, United States

Location

Helen F. Graham Cancer Center

Newark, Delaware, 19713, United States

Location

UF Health Cancer Center

Orlando, Florida, 32806, United States

Location

Columbus Regional Research Institute

Columbus, Georgia, 31904, United States

Location

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

St. Vincent Anderson Regional, Cancer Center

Anderson, Indiana, 46016, United States

Location

Norton Cancer Institute, Multicisciplinary Clinic

Louisville, Kentucky, 40202, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Willis-Knighton Cancer Center

Shreveport, Louisiana, 71103, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109-5008, United States

Location

Comprehensive Cancer Centers of Nevada-Henderson

Henderson, Nevada, 89052, United States

Location

Renown Regional Medical Center

Reno, Nevada, 89502, United States

Location

Northwell Health Cancer Institute / Center for Novel Cancer Therapeutics

Lake Success, New York, 11042, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Montefiore Medical Center, Albert Einstein College of Medicine, Department of Radiation Oncology

The Bronx, New York, 10467, United States

Location

Caromont Regional Medical Center

Gastonia, North Carolina, 28054, United States

Location

East Carolina Univ School of Dental Medicine

Greenville, North Carolina, 27834-4354, United States

Location

Mercy Medical Center

Canton, Ohio, 44708, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Temple University Hospital, Radiation Oncology

Philadelphia, Pennsylvania, 19140, United States

Location

UPMC Shadyside Hospital

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Hospital

Salt Lake City, Utah, 84112, United States

Location

Radiation Oncology Moser

Charlottesville, Virginia, 22903, United States

Location

PeaceHealth St. Joseph Medical Center

Bellingham, Washington, 98225, United States

Location

Multicare Health Center

Gig Harbor, Washington, 98405, United States

Location

Cancer Care NW

Spokane, Washington, 99216, United States

Location

Jules Bordet Institute

Brussels, 1000, Belgium

Location

University Hospital Brussels

Brussels, 1090, Belgium

Location

University Hospital Antwerp

Edegem, 2650, Belgium

Location

University Hospitals Leuven

Leuven, 3000, Belgium

Location

St. Maarten General Hospital

Mechelen, 2800, Belgium

Location

University Hospital Aachen

Aachen, 52074, Germany

Location

Amper Hospital

Dachau, 85221, Germany

Location

University Hospital Freiburg

Freiburg im Breisgau, 79106, Germany

Location

University Hospital Giessen and Marburg

Giessen, 35392, Germany

Location

Hospital Kassel

Kassel, 34125, Germany

Location

University Hospital Schleswig-Holstein

Kiel, 24105, Germany

Location

Helios Hospital Krefeld

Krefeld, 47805, Germany

Location

University Hospital Johannes Gutenberg - University of Mainz

Mainz, 55131, Germany

Location

University Hospital Mannheim

Mannheim, 68167, Germany

Location

Clinics Maria Hilf - Hospital St. Franziskus

Mönchengladbach, 41063, Germany

Location

Ludwig Maximilians University Hospital

Munich, 81377, Germany

Location

University Hospital Regensburg

Regensburg, 93053, Germany

Location

Caritas Klinikum

Saarbrücken, 85221, Germany

Location

Derriford Hospital

Plymouth, Devon, PL6 8DH, United Kingdom

Location

Beatson West of Scotland Cancer Center

Glasgow, G12 0YN, United Kingdom

Location

Guy's Hospital

London, SE1 9RT, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Royal Cornwall Hospital

Truro, TR1 3LJ, United Kingdom

Location

Related Publications (2)

• Limaye SA, Haddad RI, Cilli F, Sonis ST, Colevas AD, Brennan MT, Hu KS, Murphy BA. Phase 1b, multicenter, single blinded, placebo-controlled, sequential dose escalation study to assess the safety and tolerability of topically applied AG013 in subjects with locally advanced head and neck cancer receiving induction chemotherapy. Cancer. 2013 Dec 15;119(24):4268-76. doi: 10.1002/cncr.28365. Epub 2013 Sep 24.

  PMID: 24114811 RESULT

• Alexander LM, van Pijkeren JP. Modes of therapeutic delivery in synthetic microbiology. Trends Microbiol. 2023 Feb;31(2):197-211. doi: 10.1016/j.tim.2022.09.003. Epub 2022 Oct 8.

  PMID: 36220750 DERIVED

MeSH Terms

Conditions

Stomatitis

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases

Results Point of Contact

• Title: Dr. Alan Jolyn
• Organization: Oragenics, Inc.

info@oragenics.com

+ 1 813-286-7900

Study Officials

• Alan Joslyn, Ph.D.

  Sponsor GmbH

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2017
• First Posted: July 31, 2017
• Study Start: July 18, 2017
• Primary Completion: March 31, 2020
• Study Completion: July 13, 2020
• Last Updated: November 23, 2020
• Results First Posted: November 23, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (13); US (27); BE (5); GB (5)