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

Phase 2

Recruiting

• Conditions: Grade 2 and 3 Late Xerostomia Caused by Radiotherapy for Cancers of the Upper Aerodigestive Tract, Excluding the Parotid Glands
• Interventions: Other: Placebo; Genetic: AAV2-hAQP1 Concentration 2; Genetic: AAV2-hAQP1 Concentration 1

• Registration Number: NCT05926765
• Lead Sponsor: MeiraGTx, LLC

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-06-13
• Study First Submitted: 2023-06-22
• Study First Submitted QC: 2023-06-22
• Study First Posted: 2023-07-03
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-03
• Last Update Posted: 2024-10-08
• Primary Completion: 2025-07
• Study Completion: 2025-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

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

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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%)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo group	Placebo	Eligible participants will receive up to 3 mL of diluent via Stensen's duct to each parotid gland
AAV2-hAQP1 Group 2	AAV2-hAQP1 Concentration 2	Eligible participants will receive up to 3 mL of concentration 1 of AAV2-hAQP1 via Stensen's duct to each parotid gland
AAV2-hAQP1 Group 1	AAV2-hAQP1 Concentration 1	Eligible participants will receive up to 3 mL of concentration 1 of AAV2-hAQP1 via Stensen's duct to each parotid gland

Primary Outcome Measures

Name	Time	Method
Change from Baseline to Month 12 in Xerostomia-specific Questionnaire (XQ) Total Score	12 months	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.

Secondary Outcome Measures

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

Trial Locations

Locations (22)

City of Hope; 🇺🇸 Duarte, California, United States

Henry Ford Health; 🇺🇸 Detroit, Michigan, United States

UNC-Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States

Penn State; 🇺🇸 Hershey, Pennsylvania, United States

Houston Methodist; 🇺🇸 Houston, Texas, United States

CIUSSS-MCQ (Trois-Rivières, QC); 🇨🇦 Trois-Rivières, Canada

Addenbrooke's Hospital; 🇬🇧 Cambridge, United Kingdom

Ninewells Hospital & Medical School; 🇬🇧 Dundee, United Kingdom

Western General; 🇬🇧 London, United Kingdom

Guys Hospital; 🇬🇧 London, United Kingdom

Nottingham University Hospitals NHS Trust; 🇬🇧 Nottingham, United Kingdom

Banner MD Anderson Cancer Center; 🇺🇸 Gilbert, Arizona, United States

Miami Cancer Institute at Baptist Health South Florida; 🇺🇸 Miami, Florida, United States

University of Iowa; 🇺🇸 Iowa City, Iowa, United States

Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Missouri; 🇺🇸 Columbia, Missouri, United States

Erie County Medical Center; 🇺🇸 Buffalo, New York, United States

Atrium Health; 🇺🇸 Charlotte, North Carolina, United States

Alleghany General Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Shirley and Jim Fielding Northeast Cancer Centre - Health Sciences North; 🇨🇦 Sudbury, Ontario, Canada