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

Oral Mucositis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03234465
• Other study ID #: AG013-ODOM-201
• Status: Terminated
• Phase: Phase 2
• Start date: July 18, 2017
• Est. completion date: July 13, 2020

Study information

• Verified date: October 2020
• Source: Oragenics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 200
• Est. completion date: July 13, 2020
• Est. primary completion date: March 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Mucositis
• Oral Mucositis
• Stomatitis

Intervention

Biological:
• AG013
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.

Other:
• Placebo
Subjects assigned to the placebo group will receive appearance- and taste-matched placebo powder.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Oragenics, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  United Kingdom, 

References & Publications (1)

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 wit — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.