Safety of a Single Administration of AAV2hAQP1, an Adeno-Associated Viral Vector Encoding Human Aquaporin-1 to One Parotid Salivary Gland in People With Irradiation-Induced Parotid Salivary Hypofunction

NCT02446249 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: 15012915-D-0129
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Radiation can cause the parotid salivary glands to make less saliva (dry mouth). This can cause problems like infections and tooth decay. Researchers hope a new drug can help people with dry mouth caused by radiation. Objectives: \- To examine the safety of AAV2hAQP1 gene therapy. To see if the drug increases saliva in people whose parotid glands have had radiation. Eligibility: \- People at least 18 years of age with a history of radiation therapy for head and neck cancer. Design: Participants will be screened in 2 visits with:

• medical history
• physical exam
• scans of the head, neck, and chest
• intravenous administration of glycopyrrolate to stop saliva
• saliva collections
• sialogram which is a procedure in which a substance is injected in the parotid gland and X-rays are taken.
• non-drug infusion
• a small piece of skin being taken 3-5-day hospital stay: Participants will receive the gene infusion. The AAV2hAQP1 will be in a solution in a syringe. It will be slowly pushed into the parotid gland through the parotid duct, an opening in the mouth near the second upper molar tooth. 10 outpatient visits over 3 years. These may include:
• repeats of selected screening tests, including saliva collection
• blood and urine tests
• oral and dental examinations
• head and neck exams, including the use of a thin scope to see the back of the throat
• questionnaires
• a small piece of parotid tissue being taken by either a small scope through the parotid duct or by a small needle guided by ultrasound
• scans of the head and neck. For some, contrast will be injected in a vein
• completion of a diary about how the participant feels between visits
• swabs of teeth and gums to assess the microbiome of the mouth

Conditions

Squamous Cell Head and Neck Cancer; Radiation Induced Xerostomia; Salivary Hypofunction

Keywords

Gene Therapy; Xerostomia

Outcome Measures

Primary Outcomes (1)

• Safety of vector

  36 months

Secondary Outcomes (1)

• Efficacy of treatment

  36 months

Study Arms (1)

single arm dose escalation

EXPERIMENTAL

single arm dose escalation

Biological: AAV2hAQP1

Interventions

AAV2hAQP1 BIOLOGICAL

Infusion of gene therapy

single arm dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age
• History of external beam radiation therapy for head and neck cancer, with a mean dose equal to or greater than 15 Gy to a parotid gland.
• 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 primary malignancy by otolaryngology (ENT) assessment. Additionally, all patients must have been disease-free of head and neck cancer for at least 5 years, a status to be determined at pre-dose screening using negative clinical exams and PET and or CT imaging of the neck and chest. The anatomic subset of HPV positive oropharyngeal cancer may be enrolled after 2 years post completion of therapy.
• Willingness to practice the required birth control method ("barrier" contraception, condoms, diaphragm) until AAV2hAQP1 is no longer detectable in their serum or saliva.
• Women who cannot bear children (post-menopausal or due to a surgical intervention) also will be required to practice barrier birth control methods until AAV2hAQP1 is no longer detectable in their serum or saliva.
• Ability to stay at the NIH hospital for the period of time necessary to complete each on-site phase of the protocol (3-5 days).
• No history of allergies to any medications or agents to be used in this protocol.
• On stable medications (greater than or equal to 2 months) for any underlying medical conditions at time of vector administration.

You may not qualify if:

• Pregnant or lactating women. Women of childbearing potential are required to have a negative serum pregnancy test at screening and a negative urine pregnancy test within 48 hours prior to gene infusion.
• Any experimental therapy within 3 months.
• Any active respiratory tract infection in the 3 weeks prior to day 1 of the protocol
• Active infection that requires the use of intravenous antibiotics and does not resolve at least 1 week before Day 1.
• Uncontrolled ischemic heart disease: unstable angina, evidence of active ischemic heart disease on ECG, congestive heart failure (left ventricular ejection fraction \< 45% on MUGA or echo) or cardiomyopathy.
• Asthma or chronic obstructive pulmonary disease requiring regular inhaled or systemic corticosteroids.
• Individuals with a history of autoimmune diseases affecting salivary glands, including Sjogren's syndrome, lupus, scleroderma, type I diabetes, sarcoidosis, amyloidosis, and chronic graft versus host disease. Organ specific autoimmune conditions may be included if clinically stable.
• Use of systemic immunosuppressive medications (,i.e., corticosteroids). Topical corticosteroids are allowed.
• Malignancy, other than head and neck, within 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, hepatitis C, or human immunodeficiency virus (HIV) infection.
• WBC \<3000/microL or ANC \<1500/microL or Hgb \<10.0 g/dL or platelets \<100,000/microL or absolute lymphocyte count less than or equal to 500/microL.
• ALT and/or AST \> 1.5 times upper limit of normal (ULN) or alkaline phosphatase \>1.5 times ULN
• Serum creatinine \> 2 mg/dL.
• Serum bilirubin measurements (total, direct, indirect) that are outside of the normal range.
• Individuals who are active cigarette smokers as determined by self-reporting.

Sponsors & Collaborators

• MeiraGTx, LLC: lead
• National Institute of Dental and Craniofacial Research (NIDCR): collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Gao R, Yan X, Zheng C, Goldsmith CM, Afione S, Hai B, Xu J, Zhou J, Zhang C, Chiorini JA, Baum BJ, Wang S. AAV2-mediated transfer of the human aquaporin-1 cDNA restores fluid secretion from irradiated miniature pig parotid glands. Gene Ther. 2011 Jan;18(1):38-42. doi: 10.1038/gt.2010.128. Epub 2010 Sep 30.

  PMID: 20882054 BACKGROUND

• Baum BJ, Alevizos I, Zheng C, Cotrim AP, Liu S, McCullagh L, Goldsmith CM, Burbelo PD, Citrin DE, Mitchell JB, Nottingham LK, Rudy SF, Van Waes C, Whatley MA, Brahim JS, Chiorini JA, Danielides S, Turner RJ, Patronas NJ, Chen CC, Nikolov NP, Illei GG. Early responses to adenoviral-mediated transfer of the aquaporin-1 cDNA for radiation-induced salivary hypofunction. Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):19403-7. doi: 10.1073/pnas.1210662109. Epub 2012 Nov 5.

  PMID: 23129637 BACKGROUND

• Delporte C, O'Connell BC, He X, Lancaster HE, O'Connell AC, Agre P, Baum BJ. Increased fluid secretion after adenoviral-mediated transfer of the aquaporin-1 cDNA to irradiated rat salivary glands. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3268-73. doi: 10.1073/pnas.94.7.3268.

  PMID: 9096382 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Head and Neck Neoplasms; Xerostomia

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases

Study Officials

• John A Chiorini, Ph.D.

  National Institute of Dental and Craniofacial Research (NIDCR)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2015
• First Posted: May 18, 2015
• Study Start: May 4, 2015
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: September 25, 2025

Record last verified: 2025-09

Locations

US (1)