Study to Assess Safety and Tolerability of AG013 in Oral Mucositis in Subjects Receiving Induction Chemotherapy for the Treatment of Cancers of the Head and Neck

The purpose of this study is to assess the safety and tolerability of AG013 (genetically modified L. lactis bacteria engineered to secrete human Trefoil Factor 1), and to explore the ability of AG013 to attenuate the course and severity of oral mucositis (OM) in subjects receiving induction chemotherapy for the treatment of head and neck cancer.

The purpose of this study is to investigate the safety and tolerability of AG013 in subjects who are at risk for oral mucositis (OM) and to assess clinical efficacy of AG013 in the reduction of signs and symptoms of OM in patients receiving induction chemotherapy for the treatment of their head and neck cancer.

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.

The proposed Phase 1b clinical trial will enroll subjects with head and neck cancer who develop OM during their first cycle of treatment with induction chemotherapy. OM is a painful, common toxicity of many forms of drug and radiation therapy used for the treatment of cancer. Subjects with OM get soreness, irritation, and ulcers in the mouth and may have difficulties eating, drinking or swallowing as a result of their cancer treatment.

During the second cycle of induction chemotherapy, eligible subjects will receive AG013 or placebo for 14 consecutive days at a frequency of one rinse, three rinses or six rinses per day (sequential dose escalation design).

At least 21 subjects will be enrolled in the study. For each of the three daily dose levels, 5 subjects will be assigned to AG013 (n=5) and 2 subjects will be assigned to placebo (n=2).

Throughout the study, safety will be monitored by collecting and recording Adverse Events, laboratory assessments and the presence of sAGX0085 bacteria in blood.

An independent Data Safety Monitoring Board (DSMB) will be constituted before the enrollment of subjects in order to review safety data from each enrollment group.

• Biological: AG013
  Mouth rinse once a day for 14 days
• Biological: AG013
  Mouth rinse three times a day for 14 days
• Biological: AG013
  Mouth rinse six times a day for 14 days
• Other: Placebo
  Mouth rinse once a day for 14 days
• Other: Placebo
  Mouth rinse three times a day for 14 days
• Other: Placebo
  Mouth rinse six times a day for 14 days

• Experimental: AG013: one mouth rinse/day
  Intervention: Biological: AG013
• Experimental: AG013: three mouth rinses/day
  Intervention: Biological: AG013
• Experimental: AG013: six mouth rinses/day
  Intervention: Biological: AG013
• Placebo Comparator: one mouth rinse/day
  Intervention: Other: Placebo
• Placebo Comparator: three mouth rinses/day
  Intervention: Other: Placebo
• Placebo Comparator: six mouth rinses/day
  Intervention: Other: Placebo

Inclusion Criteria:

• Willing and able to understand and sign the study specific Informed Consent Form (ICF) approved by the site's Institutional Review Board
• Males or females 18 years or older
• Recently diagnosed with pathologically-confirmed squamous cell carcinoma of the head and neck (e.g., oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, lips, sinuses, salivary glands, unknown primary)
• Planned to receive at least two cycles of induction chemotherapy of the same regimen consisting of cisplatin/fluorouracil (PF) or cisplatin/fluorouracil/docetaxel (PFT). The planned CT cycles must be of the same length and must be a minimum of 14 days in length
• Karnofsky performance score ≥ 60%
• Screening laboratory assessments:
• Hemoglobin ≥ 10g/dl
• White blood count ≥ 3500 cells/mm3
• Absolute neutrophil counts ≥ 1500 cells/ mm3
• Direct bilirubin ≤ 2x upper limit of normal (ULN)
• Serum AST and ALT ≤ 3 x ULN
• Serum creatinine ≤ 2 mg/dl
• Serum pregnancy test: negative for females of childbearing potential: A women is considered to be of child bearing potential unless she has had a tubal ligation or is postmenopausal (without a menstrual period for at least one year)
• Subjects of childbearing potential must agree to utilize effective contraceptive methods of birth control during study participation and for 30 days following the last treatment with IMP
• Have documented mouth pain during CT Cycle 1 (i.e., OMDQ question 2 score of ≥ 2 during CT Cycle 1)

Exclusion Criteria:

• Prior radiation to the head and neck
• Chemotherapy within 21 days prior to study start
• Presence of active infectious disease excluding oral candidiasis
• Current use of antibiotic rinses or troches
• Alcohol abuse syndrome; recovered alcoholics may be included
• Presence of OM (WHO Grade > 0)
• Chronic immunosuppression
• Known seropositive for HIV or hepatitis B or C
• Use of investigational agent within 30 days of signing informed consent
• Teeth extractions within 7 days prior to the start of CT administration
• Female subjects who are pregnant or nursing
• Known sensitivity to any investigational agent
• 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