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Squamous Cell Head and Neck CancerPhase 1NCT02446249

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

A Phase 1 study testing AAV2hAQP1 in people with Squamous Cell Head and Neck Cancer and Radiation Induced Xerostomia, run by MeiraGTx, LLC at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
AAV2hAQP1
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteUnited States
Study dates
4 May 2015to 10 Aug 2026
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • Individuals who have an allergy to iodine or shellfish and thus are unable to have sialographic evaluations.
  • Individuals who have an allergy or hypersensitivity to glycopyrrolate
  • Individuals whose parotid duct(s) are not clinically accessible on screening sialography.
  • Individuals, who on sialography, have a distal stenosis that would impede vector delivery and, for the expansion cohort, those who have a parotid volume >2.5 mL.
  • Significant concurrent or recently diagnosed (<2 months) medical condition that, in the opinion of the Medically Responsible Investigator, could affect the patient's ability to tolerate or complete the study.
  • Live vaccines within 4 weeks of first infusion.
  • Individuals who have had an adverse response to prednisone (i.e. hallucinations).
  • Individuals with uncontrolled diabetes (HbA1c greater than 10%).
  • Individuals with untreated severe dental caries, pyorrhea, gingivitis, chronic radiation mucositis or ulceration, erythroplasia, leukoplakia or other pre-malignant conditions.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Open-Label, Dose-Escalation Study Evaluating the Safety of a Single Administration of an Adeno-Associated Virus Vector Encoding Human Aquaporin-1 to One Parotid Salivary Gland in Individuals With Irradiation-Induced Parotid Salivary Hypofunction

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.
Read more

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
Read the detailed description

The treatment of most head and neck cancer patients includes ionizing radiation (IR). Salivary glands in the IR field suffer irreversible damage. There is no conventional treatment available to correct this condition. Our research group has been developing an adeno-associated virus vector based on the hypothesis that this vector is capable of safely transferring the human aquaporin-1 (hAQP1) cDNA gene to parotid glands of adult patients with IR-induced salivary hypofunction, resulting in an elevated salivary output. Human AQP1 is a plasma membrane protein that facilitates water movement across lipid bilayers. Minipig studies have shown that the AAV2hAQP1 strategy for restoring salivary flow to IR-damaged salivary glands is effective without untoward effects after salivary gland delivery. As a proof of concept that AQP1 would restore saliva flow in a human population, we recently completed a phase 1 clinical trial (06-D-0206) using an Adenovirus-based vector encoding AQP1 to a single previously irradiated parotid gland in eleven patients using an open label, single dose, dose-escalation design. All patients tolerated vector delivery and study procedures well and positive objective and subjective responses were seen in five patients, all at doses <5.8 times10(9) vp/gland. At higher doses the patients possibly initiated an immune response to the vector and no improvement in gland function was observed. These findings have encouraged us to pursue studies with AAV2 based vectors, which have demonstrated lower immunogenicity and more stable expression compared with adenoviral vectors. The purpose of this clinical protocol is to test the safety of AAV2hAQP1, with some measures of efficacy, in adult patients with established IR-induced parotid gland hypofunction. The targeted tissue site for the AAV2hAQP1 vector in the proposed study is a single parotid gland. In this Phase 1 dose-escalation study, safety will be evaluated using conventional clinical and immunological parameters. The primary outcome measure for biological efficacy will be parotid gland salivary output.

Being tested
AAV2hAQP1
Keywords
Gene Therapy, Xerostomia
Medical subject headings
Head and Neck Neoplasms, Xerostomia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AAV2hAQP1Biological

    Infusion of gene therapy

Study groups in NCT02446249
Study groupRoleWhat they receive
single arm dose escalationExperimentalsingle arm dose escalation
Receives: Biological: AAV2hAQP1

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety of vector

    Measured: 36 months

Secondary outcomes (1)

  1. Efficacy of treatment

    Measured: 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 May 2015 (estimated)
  2. Study start4 May 2015
  3. Primary completion10 Aug 2026
  4. Study completion10 Aug 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02446249
Sponsor's protocol ID
150129
Other IDs
15-D-0129
Status last verified
Aug 2026
First submitted
14 May 2015
Last updated
24 Aug 2026
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 20882054

  • 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.

    PubMed 23129637

  • 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.

    PubMed 9096382

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AAV2hAQP1 in people with Squamous Cell Head and Neck Cancer and Radiation Induced Xerostomia, run by MeiraGTx, LLC at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of vector (time frame: 36 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02446249, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2026.

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