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
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|ClinicalTrials.gov Identifier: NCT02446249|
Recruitment Status : Recruiting
First Posted : May 18, 2015
Last Update Posted : May 4, 2022
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- 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.
- To examine the safety of AAV2hAQP1 gene therapy. To see if the drug increases saliva in people whose parotid glands have had radiation.
- People at least 18 years of age with a history of radiation therapy for head and neck cancer.
Participants will be screened in 2 visits with:
- medical history
- physical exam
- saliva collections
- sialogram. A substance is injected in the parotid gland and X-rays are taken.
- non-drug infusion
- IV dose of glycopyrrolate to stop saliva
3-day hospital stay: Participants will get the gene infusion. The AAV2hAQP1 will be in a solution in a syringe. It will be slowly pushed through an opening into the gland inside your mouth.
10 outpatient visits over 3 years. These may include:
- repeats of screening tests
- blood and urine tests
- oral and head and neck exams, including a thin scope in the airway
- small piece of skin taken
- small piece of parotid tissue taken by either: a small video-scope in the parotid duct that also takes pictures or by a small needle guided by ultrasound
- scans. Participants lie in a machine or a scanner The machine may feel close to the body or face. . For some, a substance will be injected in a vein or put in the mouth.
- Participants will keep a diary about how they feel before and after the therapy.
- oral microbiome gingival and buccal swab
|Condition or disease||Intervention/treatment||Phase|
|Squamous Cell Head and Neck Cancer Radiation Induced Xerostomia Salivary Hypofunction||Biological: AAV2hAQP1||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||May 4, 2015|
|Estimated Primary Completion Date :||July 2025|
|Estimated Study Completion Date :||July 2025|
Experimental: single arm dose escalation
single arm dose escalation
Infusion of gene therapy
- Safety of vector [ Time Frame: 36 months ]
- Efficacy of treatment [ Time Frame: 36 months ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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.
- 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.
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02446249
|Contact: Katherine Hall, R.N., MSNemail@example.com|
|Contact: John A Chiorini, Ph.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||John A Chiorini, Ph.D.||National Institute of Dental and Craniofacial Research (NIDCR)|
|Responsible Party:||MeiraGTx UK II Ltd|
|Other Study ID Numbers:||
15-D-0129 ( Other Identifier: NIDCR )
|First Posted:||May 18, 2015 Key Record Dates|
|Last Update Posted:||May 4, 2022|
|Last Verified:||May 2022|
Salivary Gland Diseases