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
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 x 10^11 vg/gland (single gland)
|
Drug: AAV2hAQP1: 1 x 10^11 vg/gland (single gland)
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
|
| Experimental: 3 x 10^10 vg/gland (both glands)
|
Drug: AAV2hAQP1: 3 x 10^10 vg/gland (both glands)
Intra-parotid administration of AAV2hAQP1 via Stensen's duct to both parotid glands at a dose level of 3 x 10^10 vg/gland
|
| Experimental: 3 x 10^11 vg/gland (single gland)
|
Drug: AAV2hAQP1: 3 x 10^11 vg/gland (single 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
|
| Experimental: 1 x 10^11 vg/gland (both glands)
|
Drug: AAV2hAQP1: 1 x 10^11 vg/gland (both glands)
intra-parotid administration of AAV2hAQP1 via Stensen's duct to both parotid glands at a dose level of 1 x 10^11 vg/gland
|
| Experimental: 1 x 10^12 vg/gland (single gland)
|
Drug: AAV2hAQP1: 1 x 10^12 vg/gland (single 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
|
| Experimental: 3 x 10^11 vg/gland (both glands)
|
Drug: AAV2hAQP1: 3 x 10^11 vg/gland (both glands)
Intra-parotid administration of AAV2hAQP1 via Stensen's duct to both parotid glands at a dose level of 3 x 10^11 vg/gland
|
| Experimental: 3 x 10^12 vg/gland (single gland)
|
Drug: AAV2hAQP1: 3 x 10^12 vg/gland (single 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
|
| Experimental: 1 x 10^12 vg/gland (both glands)
|
Drug: AAV2hAQP1: 1 x 10^12 vg/gland (both glands)
Intra-parotid administration of AAV2hAQP1 via Stensen's duct to both parotid glands at a dose level of 1 x 10^12 vg/gland
|
Outcome Measures
Primary Outcome Measures
- The primary outcome is safety of AAV2hAQP1 administered to the parotid gland of adult subjects with radiation-induced xerostomia [one day to one year]
Safety will be assessed by number of adverse events occurring with treatment
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Louisville | Louisville | Kentucky | United States | 40202 |
| 2 | Brigham and Women's Hospital | Boston | Massachusetts | United States | 02184 |
| 3 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 4 | Atrium Health | Charlotte | North Carolina | United States | 28209 |
| 5 | Health Sciences North - Northeast Cancer Center | Sudbury | Ontario | Canada |
Sponsors and Collaborators
- MeiraGTx UK II Ltd
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MGT016