Clinical trial NCT05926765: A Study of AAV2-hAQP1 Gene Therapy in Participants With Radiation-Induced Late Xerostomia
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Grade 2 and 3 Late Xerostomia Caused by Radiotherapy for Cancers of the Upper Aerodigestive Tract, Excluding the Parotid Glands
Lead sponsor: MeiraGTx UK II Ltd
Sponsor class: INDUSTRY
First posted: 2023-07-03
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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%)

Primary outcomes:
measure: Change from Baseline to Month 12 in Xerostomia-specific Questionnaire (XQ) Total Score
timeFrame: 12 months
Secondary outcomes:
measure: Change from Baseline to Month 12 in unstimulated whole saliva flow rate
timeFrame: 12 months
measure: Number of participants with treatment-emergent adverse events (AEs) and serious adverse events (SAEs)
timeFrame: from Baseline to Month 12
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Miami
country: United States
facility: Miami Cancer Institute at Baptist Health South Florida
state: Florida
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health
state: Michigan
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: Buffalo
country: United States
facility: Erie County Medical Center
state: New York
city: Chapel Hill
country: United States
facility: UNC-Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Atrium Health
state: North Carolina
city: Hershey
country: United States
facility: Penn State
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Alleghany General Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist
state: Texas
city: Sudbury
country: Canada
facility: Shirley and Jim Fielding Northeast Cancer Centre - Health Sciences North
state: Ontario
city: Trois-Rivières
country: Canada
facility: CIUSSS-MCQ (Trois-Rivières, QC)
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Dundee
country: United Kingdom
facility: Ninewells Hospital & Medical School
city: London
country: United Kingdom
facility: Western General
city: London
country: United Kingdom
facility: Guys Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
Study officials:
References: