Clinical trial NCT03234465: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Oral Mucositis
Lead sponsor: Oragenics, Inc.
Sponsor class: INDUSTRY
First posted: 2017-07-31
Enrollment: 200
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
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)
timeFrame: From the start of radiation therapy (RT) until 2 weeks following its completion, 7 to 9 weeks depending on the duration of CRT.
Secondary outcomes:
Other outcomes:
Locations:
city: Farmington
country: United States
facility: University of Connecticut Health Center
state: Connecticut
city: Newark
country: United States
facility: Helen F. Graham Cancer Center
state: Delaware
city: Orlando
country: United States
facility: UF Health Cancer Center
state: Florida
city: Columbus
country: United States
facility: Columbus Regional Research Institute
state: Georgia
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Anderson
country: United States
facility: St. Vincent Anderson Regional, Cancer Center
state: Indiana
city: Louisville
country: United States
facility: Norton Cancer Institute, Multicisciplinary Clinic
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Shreveport
country: United States
facility: Willis-Knighton Cancer Center
state: Louisiana
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada-Henderson
state: Nevada
city: Reno
country: United States
facility: Renown Regional Medical Center
state: Nevada
city: Bronx
country: United States
facility: Montefiore Medical Center, Albert Einstein College of Medicine, Department of Radiation Oncology
state: New York
city: Lake Success
country: United States
facility: Northwell Health Cancer Institute / Center for Novel Cancer Therapeutics
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Gastonia
country: United States
facility: Caromont Regional Medical Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina Univ School of Dental Medicine
state: North Carolina
city: Canton
country: United States
facility: Mercy Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: Temple University Hospital, Radiation Oncology
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Shadyside Hospital
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Hospital
state: Utah
city: Charlottesville
country: United States
facility: Radiation Oncology Moser
state: Virginia
city: Bellingham
country: United States
facility: PeaceHealth St. Joseph Medical Center
state: Washington
city: Gig Harbor
country: United States
facility: Multicare Health Center
state: Washington
city: Spokane
country: United States
facility: Cancer Care NW
state: Washington
city: Brussels
country: Belgium
facility: Jules Bordet Institute
city: Brussels
country: Belgium
facility: University Hospital Brussels
city: Edegem
country: Belgium
facility: University Hospital Antwerp
city: Leuven
country: Belgium
facility: University Hospitals Leuven
city: Mechelen
country: Belgium
facility: St. Maarten General Hospital
city: Aachen
country: Germany
facility: University Hospital Aachen
city: Dachau
country: Germany
facility: Amper Hospital
city: Freiburg
country: Germany
facility: University Hospital Freiburg
city: Gießen
country: Germany
facility: University Hospital Giessen and Marburg
city: Kassel
country: Germany
facility: Hospital Kassel
city: Kiel
country: Germany
facility: University Hospital Schleswig-Holstein
city: Krefeld
country: Germany
facility: Helios Hospital Krefeld
city: Mainz
country: Germany
facility: University Hospital Johannes Gutenberg - University of Mainz
city: Mannheim
country: Germany
facility: University Hospital Mannheim
city: Munich
country: Germany
facility: Ludwig Maximilians University Hospital
city: Mönchengladbach
country: Germany
facility: Clinics Maria Hilf - Hospital St. Franziskus
city: Regensburg
country: Germany
facility: University Hospital Regensburg
city: Saarbrücken
country: Germany
facility: Caritas Klinikum
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: Devon
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Center
city: London
country: United Kingdom
facility: Guy's Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
Study officials:
affiliation: Sponsor GmbH
name: Alan Joslyn, Ph.D.
role: STUDY_DIRECTOR
References:
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.