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

Primary Purpose

Oral Mucositis

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AG013
Placebo
Sponsored by
Oragenics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Oral Mucositis

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Connecticut Health Center
  • Helen F. Graham Cancer Center
  • UF Health Cancer Center
  • Columbus Regional Research Institute
  • Decatur Memorial Hospital
  • St. Vincent Anderson Regional, Cancer Center
  • Norton Cancer Institute, Multicisciplinary Clinic
  • Ochsner Clinic Foundation
  • Willis-Knighton Cancer Center
  • University of Michigan
  • Comprehensive Cancer Centers of Nevada-Henderson
  • Renown Regional Medical Center
  • Montefiore Medical Center, Albert Einstein College of Medicine, Department of Radiation Oncology
  • Northwell Health Cancer Institute / Center for Novel Cancer Therapeutics
  • University of Rochester Medical Center
  • Caromont Regional Medical Center
  • East Carolina Univ School of Dental Medicine
  • Mercy Medical Center
  • Ohio State University Comprehensive Cancer Center
  • Temple University Hospital, Radiation Oncology
  • UPMC Shadyside Hospital
  • University of Texas MD Anderson Cancer Center
  • Huntsman Cancer Hospital
  • Radiation Oncology Moser
  • PeaceHealth St. Joseph Medical Center
  • Multicare Health Center
  • Cancer Care NW
  • Jules Bordet Institute
  • University Hospital Brussels
  • University Hospital Antwerp
  • University Hospitals Leuven
  • St. Maarten General Hospital
  • University Hospital Aachen
  • Amper Hospital
  • University Hospital Freiburg
  • University Hospital Giessen and Marburg
  • Hospital Kassel
  • University Hospital Schleswig-Holstein
  • Helios Hospital Krefeld
  • University Hospital Johannes Gutenberg - University of Mainz
  • University Hospital Mannheim
  • Ludwig Maximilians University Hospital
  • Clinics Maria Hilf - Hospital St. Franziskus
  • University Hospital Regensburg
  • Caritas Klinikum
  • Derriford Hospital
  • Beatson West of Scotland Cancer Center
  • Guy's Hospital
  • The Christie NHS Foundation Trust
  • Royal Cornwall Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

AG013: three mouth rinses/day

Placebo: three mouth rinses/day

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Full Information

First Posted
July 21, 2017
Last Updated
November 20, 2020
Sponsor
Oragenics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03234465
Brief Title
Efficacy, Safety and Tolerability of AG013 in Oral Mucositis Compared to Placebo When Administered Three Times Per Day
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Terminated
Why Stopped
No efficacy could be demonstrated, sponsor decided to prematurely end the study.
Study Start Date
July 18, 2017 (Actual)
Primary Completion Date
March 31, 2020 (Actual)
Study Completion Date
July 13, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Oragenics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oral Mucositis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
200 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AG013: three mouth rinses/day
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo: three mouth rinses/day
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
AG013
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Subjects assigned to the placebo group will receive appearance- and taste-matched placebo powder.
Primary Outcome Measure Information:
Title
Efficacy of AG013 Compared to Placebo for Reducing OM as Measured by Duration (in Days) of Severe Oral Mucositis (WHO Grades 3 or 4)
Description
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alan Joslyn, Ph.D.
Organizational Affiliation
Sponsor GmbH
Official's Role
Study Director
Facility Information:
Facility Name
University of Connecticut Health Center
City
Farmington
State/Province
Connecticut
ZIP/Postal Code
06030
Country
United States
Facility Name
Helen F. Graham Cancer Center
City
Newark
State/Province
Delaware
ZIP/Postal Code
19713
Country
United States
Facility Name
UF Health Cancer Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Columbus Regional Research Institute
City
Columbus
State/Province
Georgia
ZIP/Postal Code
31904
Country
United States
Facility Name
Decatur Memorial Hospital
City
Decatur
State/Province
Illinois
ZIP/Postal Code
62526
Country
United States
Facility Name
St. Vincent Anderson Regional, Cancer Center
City
Anderson
State/Province
Indiana
ZIP/Postal Code
46016
Country
United States
Facility Name
Norton Cancer Institute, Multicisciplinary Clinic
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Ochsner Clinic Foundation
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Willis-Knighton Cancer Center
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71103
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-5008
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada-Henderson
City
Henderson
State/Province
Nevada
ZIP/Postal Code
89052
Country
United States
Facility Name
Renown Regional Medical Center
City
Reno
State/Province
Nevada
ZIP/Postal Code
89502
Country
United States
Facility Name
Montefiore Medical Center, Albert Einstein College of Medicine, Department of Radiation Oncology
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Northwell Health Cancer Institute / Center for Novel Cancer Therapeutics
City
Lake Success
State/Province
New York
ZIP/Postal Code
11042
Country
United States
Facility Name
University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Caromont Regional Medical Center
City
Gastonia
State/Province
North Carolina
ZIP/Postal Code
28054
Country
United States
Facility Name
East Carolina Univ School of Dental Medicine
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834-4354
Country
United States
Facility Name
Mercy Medical Center
City
Canton
State/Province
Ohio
ZIP/Postal Code
44708
Country
United States
Facility Name
Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Temple University Hospital, Radiation Oncology
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
Facility Name
UPMC Shadyside Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Huntsman Cancer Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Radiation Oncology Moser
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
Facility Name
PeaceHealth St. Joseph Medical Center
City
Bellingham
State/Province
Washington
ZIP/Postal Code
98225
Country
United States
Facility Name
Multicare Health Center
City
Gig Harbor
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Facility Name
Cancer Care NW
City
Spokane
State/Province
Washington
ZIP/Postal Code
99216
Country
United States
Facility Name
Jules Bordet Institute
City
Brussels
ZIP/Postal Code
1000
Country
Belgium
Facility Name
University Hospital Brussels
City
Brussels
ZIP/Postal Code
1090
Country
Belgium
Facility Name
University Hospital Antwerp
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
Facility Name
University Hospitals Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
St. Maarten General Hospital
City
Mechelen
ZIP/Postal Code
2800
Country
Belgium
Facility Name
University Hospital Aachen
City
Aachen
ZIP/Postal Code
52074
Country
Germany
Facility Name
Amper Hospital
City
Dachau
ZIP/Postal Code
85221
Country
Germany
Facility Name
University Hospital Freiburg
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
University Hospital Giessen and Marburg
City
Gießen
ZIP/Postal Code
35392
Country
Germany
Facility Name
Hospital Kassel
City
Kassel
ZIP/Postal Code
34125
Country
Germany
Facility Name
University Hospital Schleswig-Holstein
City
Kiel
ZIP/Postal Code
24105
Country
Germany
Facility Name
Helios Hospital Krefeld
City
Krefeld
ZIP/Postal Code
47805
Country
Germany
Facility Name
University Hospital Johannes Gutenberg - University of Mainz
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
University Hospital Mannheim
City
Mannheim
ZIP/Postal Code
68167
Country
Germany
Facility Name
Ludwig Maximilians University Hospital
City
Munich
ZIP/Postal Code
81377
Country
Germany
Facility Name
Clinics Maria Hilf - Hospital St. Franziskus
City
Mönchengladbach
ZIP/Postal Code
41063
Country
Germany
Facility Name
University Hospital Regensburg
City
Regensburg
ZIP/Postal Code
93053
Country
Germany
Facility Name
Caritas Klinikum
City
Saarbrücken
ZIP/Postal Code
85221
Country
Germany
Facility Name
Derriford Hospital
City
Plymouth
State/Province
Devon
ZIP/Postal Code
PL6 8DH
Country
United Kingdom
Facility Name
Beatson West of Scotland Cancer Center
City
Glasgow
ZIP/Postal Code
G12 0YN
Country
United Kingdom
Facility Name
Guy's Hospital
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Facility Name
The Christie NHS Foundation Trust
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Facility Name
Royal Cornwall Hospital
City
Truro
ZIP/Postal Code
TR1 3LJ
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
24114811
Citation
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.
Results Reference
result

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

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