A Study of AAV2-hAQP1 Gene Therapy in Participants With Radiation-Induced Late Xerostomia

Study Overview
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Brief Summary
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This study will assess the efficacy and safety of bilateral intra-parotid administration of AAV2-hAQP1 in adults with Grade 2 or Grade 3 radiation-induced late xerostomia.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study to Determine the Efficacy and Safety of AAV2-hAQP1 Gene Therapy in Participants With Radiation-Induced Late Xerostomia

Conditions
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Grade 2 and 3 Late Xerostomia Caused by Radiotherapy for Cancers of the Upper Aerodigestive Tract, Excluding the Parotid Glands

Intervention / Treatment
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* Genetic: AAV2-hAQP1 Concentration 1
* Genetic: AAV2-hAQP1 Concentration 2
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completed beam radiation therapy for head and neck cancer at least 3 years prior to the first screening visit No history of parotid gland cancer, recurrent cancer, or a second primary cancer An unstimulated whole saliva flow rate (mL/min) >0 (i.e., at least one drop of saliva in the collection tube) A stimulated whole saliva flow rate (mL/min) within a specified range after mechanical stimulation by chewing Average screening XQ Total Score at or above a specified threshold No evidence of head and neck cancer, defined as a negative otolaryngology exam and a negative computed tomography (CT) scan of the head, neck, and chest with contrast. If a participant has had a magnetic resonance imaging (MRI) study, CT scan, positron emission tomography (PET), or fluorodeoxyglucose-positron emission tomography (FDG-PET) scan of the head, neck, and chest within 6 months of study entry (and at least 3 years after the completion of radiotherapy), then that image may be used for eligibility determination and a CT scan at screening will not be required. Either received treatment with one or more prescription sialagogues and elected to discontinue therapy or, in consultation with their physician, elected to not initiate such treatment Participants taking a prescription sialagogue (specifically, pilocarpine or cevimeline) must stop that medication at least 2 weeks prior to Screening and be willing to refrain from taking such medications for the duration of the study Participants who require medication for an underlying medical condition that is known to affect salivary output must be on stable doses of such medications for at least one month prior to the first screening visit Exclusion Criteria: Any malignancy within the preceding 3 years, except for treated basal cell or squamous cell carcinoma of the skin or in situ cervical carcinoma History of systemic autoimmune disease affecting the salivary glands (e.g., Sjogren's disease) Currently using systemic immunosuppressive medication(s) (e.g., corticosteroids or biologics) or treated with one within 4 weeks of the first screening visit. Note: Topical, inhaled, or intranasal corticosteroids are permitted. Active viral infection with Epstein-Barr virus (EBV), defined as a positive anti-VCA IgM. In the event a potential participant has a positive anti-VCA IgM, they may be rescreened 2-4 months later at which time a positive Epstein-Barr Virus Nuclear Antigen (EBNA) will be considered as evidence of resolved EBV infection. Evidence of active Hepatitis C virus (HCV) infection Evidence of human immunodeficiency virus (HIV) infection Diagnosis of myasthenia gravis Personal or family history of acute or chronic angle-closure glaucoma (ACG), or at increased risk of developing ACG, or had prophylactic treatment to reduce the risk of developing ACG Known allergy or hypersensitivity to glycopyrrolate Current smokers or history of smoking within the preceding 3 years (includes vaping with tobacco additives) Current alcohol misuse or a history of the same within the preceding 3 years (defined for men as an average intake of more than 14 drinks per week and for women as more than 7 drinks per week) Poorly controlled diabetes (hemoglobin A1c >7%)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AAV2-hAQP1 Group 1<br>Eligible participants will receive up to 3 mL of concentration 1 of AAV2-hAQP1 via Stensen's duct to each parotid gland | Genetic: AAV2-hAQP1 Concentration 1<br>* Administration of concentration 1 of AAV2-hAQP1 via Stensen's duct to each parotid gland<br>|
| Experimental: AAV2-hAQP1 Group 2<br>Eligible participants will receive up to 3 mL of concentration 1 of AAV2-hAQP1 via Stensen's duct to each parotid gland | Genetic: AAV2-hAQP1 Concentration 2<br>* Administration of concentration 2 of AAV2-hAQP1 via Stensen's duct to each parotid gland<br>|
| Placebo Comparator: Placebo group<br>Eligible participants will receive up to 3 mL of diluent via Stensen's duct to each parotid gland | Other: Placebo<br>* Administration of diluent via Stensen's duct to each parotid gland<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Month 12 in Xerostomia-specific Questionnaire (XQ) Total Score | Change from Baseline to Month 12 in Xerostomia-specific Questionnaire (XQ) Total Score. The XQ consists of 8 symptom-specific questions the participant rates from 0 (not present) to 10 (worst possible). The XQ Total Score is the sum of all individual item ratings and ranges from 0 to 80. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Month 12 in unstimulated whole saliva flow rate | Change from Baseline to Month 12 in unstimulated whole saliva flow rate (mL/min) | 12 months | 
| Number of participants with treatment-emergent adverse events (AEs) and serious adverse events (SAEs) |  | from Baseline to Month 12 |