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

• Status: Recruiting
• Trial end date: 2022-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Open-label, non-randomized, dose escalation trial of AAV2hAQP1 administered via Stensen's duct to a single parotid gland 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 targeted parotid gland:

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: MeiraGTx UK II Ltd

Criteria

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.

6. On stable medications (>2 months) for any underlying medical conditions at the time of study drug administration.

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.