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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

M

MeiraGTx

Status and phase

Completed
Phase 1

Conditions

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

Treatments

Drug: AAV2hAQP1: 1 x 10^11 vg/gland (single gland)
Drug: AAV2hAQP1: 3 x 10^12 vg/gland (single gland)
Drug: AAV2hAQP1: 3 x 10^11 vg/gland (both glands)
Drug: AAV2hAQP1: 1 x 10^12 vg/gland (both glands)
Drug: AAV2hAQP1: 1 x 10^11 vg/gland (both glands)
Drug: AAV2hAQP1: 3 x 10^11 vg/gland (single gland)
Drug: AAV2hAQP1: 1 x 10^12 vg/gland (single gland)
Drug: AAV2hAQP1: 3 x 10^10 vg/gland (both glands)

Study type

Interventional

Funder types

Industry

Identifiers

Details and patient eligibility

About

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.

Enrollment

24 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

24 participants in 8 patient groups

1 x 10^11 vg/gland (single gland)
Experimental group
Treatment:
Drug: AAV2hAQP1: 1 x 10^11 vg/gland (single gland)
3 x 10^10 vg/gland (both glands)
Experimental group
Treatment:
Drug: AAV2hAQP1: 3 x 10^10 vg/gland (both glands)
3 x 10^11 vg/gland (single gland)
Experimental group
Treatment:
Drug: AAV2hAQP1: 3 x 10^11 vg/gland (single gland)
1 x 10^11 vg/gland (both glands)
Experimental group
Treatment:
Drug: AAV2hAQP1: 1 x 10^11 vg/gland (both glands)
1 x 10^12 vg/gland (single gland)
Experimental group
Treatment:
Drug: AAV2hAQP1: 1 x 10^12 vg/gland (single gland)
3 x 10^11 vg/gland (both glands)
Experimental group
Treatment:
Drug: AAV2hAQP1: 3 x 10^11 vg/gland (both glands)
3 x 10^12 vg/gland (single gland)
Experimental group
Treatment:
Drug: AAV2hAQP1: 3 x 10^12 vg/gland (single gland)
1 x 10^12 vg/gland (both glands)
Experimental group
Treatment:
Drug: AAV2hAQP1: 1 x 10^12 vg/gland (both glands)

Trial contacts and locations

6

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Data sourced from clinicaltrials.gov

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