Efficacy, Safety and Tolerability of AG013 in Oral Mucositis Compared to Placebo When Administered Three Times Per Day
Condition: Oral Mucositis
MeSH terms: Mucositis; Stomatitis
Intervention: AG013; Placebo
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.; Subjects assigned to the placebo group will receive appearance- and taste-matched placebo powder.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 200.0
Sex: All
Minimum age: 21 Years
Healthy volunteers: No

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.
    

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