A Phase 1 Open-Label, Dose Escalation Study to Determine the Optimal Dose, Safety, and Activity of AAV2hAQP1 in Subjects With Radiation-Induced Parotid Gland Hypofunction and Xerostomia

Inclusion criteria

• Male or female subjects ≥18 years of age.
• History of radiation therapy for head and neck cancer.
• Abnormal parotid gland function as judged by both absence of unstimulated parotid salivary flow and a stimulated parotid salivary flow in the targeted parotid gland >0 and <0.3 mL/min/gland after 2% citrate stimulation.
• No evidence of recurrence of the primary malignancy by an otolaryngology (ears, nose, and throat [ENT]) assessment. Additionally, all subjects must be disease-free of head and neck cancer for at least 5 years following the end of treatment at screening, with the exception of subjects with a history of HPV+ OPC (base of tongue, oropharynx, pharynx, soft palate, tonsil) who must be disease free for at least 2 years following the end of treatment. Disease status will be determined by negative clinical examinations and computed tomography (CT) scans of the neck and chest. If subjects have had a magnetic resonance imaging (MRI) of the neck or a positron emission tomography (PET) scan within 6 months of screening, then a CT scan is not required, except for HPV+ OPC subjects who must have scans at 2 years post treatment.
• Female subjects of childbearing potential (i.e., ovulating, pre-menopausal, and not surgically sterile) and all male subjects must use a medically accepted contraceptive regimen during their participation in the study and until all samples collected at 2 consecutive visits following AAV2hAQP1 administration are negative. Acceptable methods of contraception for male subjects include the following:

• Condoms with spermicide. Acceptable methods of contraception for female subjects include the following:
• Intrauterine device for at least 12 weeks prior to Screening.
• Hormonal contraception (oral, implant, injection, ring, or patch) for at least 12 weeks prior to Screening.
• Diaphragm used in combination with spermicide.

Exclusion criteria

• Pregnant or lactating women or women planning to become pregnant.
• Any experimental therapy within 3 months before Day 1.
• Active infection that requires the use of intravenous antibiotics and does not resolve at least 1 week before Day 1.
• Uncontrolled ischemic heart disease (i.e., unstable angina, evidence of active ischemic heart disease on electrocardiogram [ECG]).
• History of systemic autoimmune diseases affecting the salivary glands.
• Use of systemic immunosuppressive medications (i.e., corticosteroids).

o Note: Topical, inhaled, or intranasal corticosteroids are allowed.

• Malignancy, other than head and neck cancer, within the past 3 years, with the exception of adequately treated basal cell or squamous cell carcinoma of the skin or in situ cervical carcinoma.
• Active infections including, Epstein-Barr virus (EBV), cytomegalovirus (CMV), hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV) infection.
• White blood cell count <3000/μL, absolute neutrophil count <1500/μL, hemoglobin <10.0 g/dL, platelet count <100,000/μL, or absolute lymphocyte count ≤500/μL.
• Alanine aminotransferase and/or aspartate aminotransferase >1.5 × the upper limit of normal (ULN), alkaline phosphatase >1.5 × ULN, or total bilirubin >1.5 × ULN with any elevation of liver enzymes.
• Estimated glomerular filtration rate <60 mL/min/1.73 m2 using the Modification of Diet in Renal Disease equation.
• Active use of tobacco products as determined by self-reporting.
• Allergy to iodine or shellfish, and thus unable to have sialographic evaluations.
• Allergy or hypersensitivity to glycopyrrolate.