Oral MucositisPhase 2NCT03234465
Efficacy, Safety and Tolerability of AG013 in Oral Mucositis Compared to Placebo When Administered Three Times Per Day
A Phase 2 study testing AG013 in people with Oral Mucositis, run by Oragenics, Inc. at 50 sites in 4 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Oral Mucositis
- What is being tested?
- AG013
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 50 sitesin 4 countries
- Study dates
- 18 Jul 2017to 13 Jul 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 16Show fewer
- 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.
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
50 sites in 4 countries.
50 sites in 4 countries
United States27 sites
St. Vincent Anderson Regional, Cancer Center
Anderson, Indiana, 46016
University of Michigan
Ann Arbor, Michigan, 48109-5008
PeaceHealth St. Joseph Medical Center
Bellingham, Washington, 98225
Mercy Medical Center
Canton, Ohio, 44708
Radiation Oncology Moser
Charlottesville, Virginia, 22903
Columbus Regional Research Institute
Columbus, Georgia, 31904
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Decatur Memorial Hospital
Decatur, Illinois, 62526
University of Connecticut Health Center
Farmington, Connecticut, 06030
Caromont Regional Medical Center
Gastonia, North Carolina, 28054
Multicare Health Center
Gig Harbor, Washington, 98405
East Carolina Univ School of Dental Medicine
Greenville, North Carolina, 27834-4354
Comprehensive Cancer Centers of Nevada-Henderson
Henderson, Nevada, 89052
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Northwell Health Cancer Institute / Center for Novel Cancer Therapeutics
Lake Success, New York, 11042
Norton Cancer Institute, Multicisciplinary Clinic
Louisville, Kentucky, 40202
Ochsner Clinic Foundation
New Orleans, Louisiana, 70121
Helen F. Graham Cancer Center
Newark, Delaware, 19713
UF Health Cancer Center
Orlando, Florida, 32806
Temple University Hospital, Radiation Oncology
Philadelphia, Pennsylvania, 19140
UPMC Shadyside Hospital
Pittsburgh, Pennsylvania, 15232
Renown Regional Medical Center
Reno, Nevada, 89502
University of Rochester Medical Center
Rochester, New York, 14642
Huntsman Cancer Hospital
Salt Lake City, Utah, 84112
Willis-Knighton Cancer Center
Shreveport, Louisiana, 71103
Cancer Care NW
Spokane, Washington, 99216
Montefiore Medical Center, Albert Einstein College of Medicine, Department of Radiation Oncology
The Bronx, New York, 10467
Germany13 sites
University Hospital Aachen
Aachen, 52074
Amper Hospital
Dachau, 85221
University Hospital Freiburg
Freiburg im Breisgau, 79106
University Hospital Giessen and Marburg
Giessen, 35392
Hospital Kassel
Kassel, 34125
University Hospital Schleswig-Holstein
Kiel, 24105
Helios Hospital Krefeld
Krefeld, 47805
University Hospital Johannes Gutenberg - University of Mainz
Mainz, 55131
University Hospital Mannheim
Mannheim, 68167
Clinics Maria Hilf - Hospital St. Franziskus
Mönchengladbach, 41063
Ludwig Maximilians University Hospital
Munich, 81377
University Hospital Regensburg
Regensburg, 93053
Caritas Klinikum
Saarbrücken, 85221
Belgium5 sites
Jules Bordet Institute
Brussels, 1000
University Hospital Brussels
Brussels, 1090
University Hospital Antwerp
Edegem, 2650
University Hospitals Leuven
Leuven, 3000
St. Maarten General Hospital
Mechelen, 2800
United Kingdom5 sites
Beatson West of Scotland Cancer Center
Glasgow, G12 0YN
Guy's Hospital
London, SE1 9RT
The Christie NHS Foundation Trust
Manchester, M20 4BX
Derriford Hospital
Plymouth, Devon, PL6 8DH
Royal Cornwall Hospital
Truro, TR1 3LJ
About this study
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
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.
Read the 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.
- Conditions
- Oral Mucositis
- Being tested
- AG013, Placebo
- Medical subject headings
- Stomatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AG013Biological
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.
PlaceboOther
Subjects assigned to the placebo group will receive appearance- and taste-matched placebo powder.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: From the start of radiation therapy (RT) until 2 weeks following its completion, 7 to 9 weeks depending on the duration of CRT.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2017
- Study start18 Jul 2017
- Primary completion31 Mar 2020
- Study completion13 Jul 2020
Why it stopped: No efficacy could be demonstrated, sponsor decided to prematurely end the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Oral MucositisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oragenics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Alan Joslyn, Ph.D., Study director, Sponsor GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03234465
- Sponsor's protocol ID
- AG013-ODOM-201
- Status last verified
- Oct 2020
- First submitted
- 21 Jul 2017
- Last updated
- 23 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 24114811Alexander 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.
PubMed 36220750
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03234465
- Acronym / sponsor ID
- AG013-ODOM-201
- Conditions
- Oral Mucositis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: No efficacy could be demonstrated, sponsor decided to prematurely end the study.
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Oragenics, Inc.Industry (pharma, biotech, devices)
- Study start
- 18 Jul 2017 (actual)
- Primary completion
- 31 Mar 2020 (actual)
- Study completion
- 13 Jul 2020 (actual)
- First posted
- 31 Jul 2017 (actual)
- Results
- Posted 23 Nov 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AG013: three mouth rinses/day | Experimental | Biological: AG013Subjects 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 comparator | Other: PlaceboSubjects 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. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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)
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AG013AG013 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. | Biological | AG013: three mouth rinses/day |
| PlaceboSubjects assigned to the placebo group will receive appearance- and taste-matched placebo powder. | Other | Placebo: three mouth rinses/day |
Primary outcome
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24114811Limaye 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.
- Derived from this study: PubMed 36220750Alexander 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alan Joslyn, Ph.D. study director
Sponsor GmbH
50 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AG013 in people with Oral Mucositis, run by Oragenics, Inc. at 50 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 50 sites in United States, Germany, Belgium, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03234465, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Nov 2020.