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

Head and Neck Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04043104
• Other study ID #: MGT016
• Status: Completed
• Phase: Phase 1
• Start date: June 30, 2019
• Est. completion date: March 28, 2023

Study information

• Verified date: April 2023
• Source: MeiraGTx UK II Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: March 28, 2023
• Est. primary completion date: March 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female subjects =18 years of age.

2. History of radiation therapy for head and neck cancer.

3. 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.

4. 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.

5. 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:

1. Pregnant or lactating women or women planning to become pregnant.

2. Any experimental therapy within 3 months before Day 1.

3. Active infection that requires the use of intravenous antibiotics and does not resolve at least 1 week before Day 1.

4. Uncontrolled ischemic heart disease (i.e., unstable angina, evidence of active ischemic heart disease on electrocardiogram [ECG]).

5. History of systemic autoimmune diseases affecting the salivary glands.

6. Use of systemic immunosuppressive medications (i.e., corticosteroids). o Note: Topical, inhaled, or intranasal corticosteroids are allowed.

7. 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.

8. Active infections including, Epstein-Barr virus (EBV), cytomegalovirus (CMV), hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV) infection.

9. 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.

10. 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.

11. Estimated glomerular filtration rate <60 mL/min/1.73 m2 using the Modification of Diet in Renal Disease equation.

12. Active use of tobacco products as determined by self-reporting.

13. Allergy to iodine or shellfish, and thus unable to have sialographic evaluations.

14. Allergy or hypersensitivity to glycopyrrolate.

Related Conditions & MeSH terms

• Head and Neck Cancer
• Radiation-Induced Parotid Gland Hypofunction
• Xerostomia
• Xerostomia Due to Radiotherapy

Intervention

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
• 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
• 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
• 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
• 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
• 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
• 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
• 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

Locations

Country	Name	City	State
Canada	Health Sciences North - Northeast Cancer Center	Sudbury	Ontario
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Atrium Health	Charlotte	North Carolina
United States	University of Louisville	Louisville	Kentucky
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Leland Stanford Junior University	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
MeiraGTx UK II Ltd

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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