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
1 other identifier
interventional
24
2 countries
6
Brief Summary
Open-label, non-randomized, dose escalation trial of AAV2hAQP1 administered via Stensen's duct to a single or both parotid glands in subjects with radiation-induced xerostomia The objectives are to evaluate the safety and identify either a maximum tolerated dose or a maximum feasible dose of a single dose of AAV2hAQP1 infused into one or both parotid glands: To evaluate subject improvement of xerostomia symptoms, to evaluate the increase in parotid gland salivary output after treatment with AAV2hAQP1, to evaluate additional efficacy outcomes.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Jun 2019
Typical duration for phase_1
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 30, 2019
CompletedFirst Submitted
Initial submission to the registry
July 23, 2019
CompletedFirst Posted
Study publicly available on registry
August 2, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 28, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
March 28, 2023
CompletedApril 24, 2023
April 1, 2023
3.7 years
July 23, 2019
April 21, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
The primary outcome is safety of AAV2hAQP1 administered to the parotid gland of adult subjects with radiation-induced xerostomia
Safety will be assessed by number of adverse events occurring with treatment
one day to one year
Study Arms (8)
1 x 10^11 vg/gland (single gland)
EXPERIMENTAL3 x 10^10 vg/gland (both glands)
EXPERIMENTAL3 x 10^11 vg/gland (single gland)
EXPERIMENTAL1 x 10^11 vg/gland (both glands)
EXPERIMENTAL1 x 10^12 vg/gland (single gland)
EXPERIMENTAL3 x 10^11 vg/gland (both glands)
EXPERIMENTAL3 x 10^12 vg/gland (single gland)
EXPERIMENTAL1 x 10^12 vg/gland (both glands)
EXPERIMENTALInterventions
Intra-parotid administration of AAV2hAQP1 via Stensen's duct to a single parotid gland at a dose level of 1 x 10\^11 vg/gland
Intra-parotid administration of AAV2hAQP1 via Stensen's duct to both parotid glands at a dose level of 3 x 10\^10 vg/gland
Intra-parotid administration of AAV2hAQP1 of via Stensen's duct to a single parotid gland at a dose level of 3 x 10\^11 vg/gland
intra-parotid administration of AAV2hAQP1 via Stensen's duct to both parotid glands at a dose level of 1 x 10\^11 vg/gland
Intra-parotid administration of AAV2hAQP1 via Stensen's duct to a single parotid gland at a dose level of 1 x 10\^12 vg/gland
Intra-parotid administration of AAV2hAQP1 via Stensen's duct to both parotid glands at a dose level of 3 x 10\^11 vg/gland
Intra-parotid administration of AAV2hAQP1 via Stensen's duct to a single parotid gland at a dose level of 3 x 10\^12 vg/gland
Intra-parotid administration of AAV2hAQP1 via Stensen's duct to both parotid glands at a dose level of 1 x 10\^12 vg/gland
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (6)
Leland Stanford Junior University
Stanford, California, 94305, United States
University of Louisville
Louisville, Kentucky, 40202, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02184, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Atrium Health
Charlotte, North Carolina, 28209, United States
Health Sciences North - Northeast Cancer Center
Greater Sudbury, Ontario, Canada
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 23, 2019
First Posted
August 2, 2019
Study Start
June 30, 2019
Primary Completion
March 28, 2023
Study Completion
March 28, 2023
Last Updated
April 24, 2023
Record last verified: 2023-04