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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

Primary Purpose

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

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
AAV2hAQP1: 1 x 10^11 vg/gland (single gland)
AAV2hAQP1: 3 x 10^10 vg/gland (both glands)
AAV2hAQP1: 3 x 10^11 vg/gland (single gland)
AAV2hAQP1: 1 x 10^11 vg/gland (both glands)
AAV2hAQP1: 1 x 10^12 vg/gland (single gland)
AAV2hAQP1: 3 x 10^11 vg/gland (both glands)
AAV2hAQP1: 3 x 10^12 vg/gland (single gland)
AAV2hAQP1: 1 x 10^12 vg/gland (both glands)
Sponsored by
MeiraGTx UK II Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Radiation-Induced Parotid Gland Hypofunction

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Leland Stanford Junior University
  • University of Louisville
  • Brigham and Women's Hospital
  • Memorial Sloan Kettering Cancer Center
  • Atrium Health
  • Health Sciences North - Northeast Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

1 x 10^11 vg/gland (single gland)

3 x 10^10 vg/gland (both glands)

3 x 10^11 vg/gland (single gland)

1 x 10^11 vg/gland (both glands)

1 x 10^12 vg/gland (single gland)

3 x 10^11 vg/gland (both glands)

3 x 10^12 vg/gland (single gland)

1 x 10^12 vg/gland (both glands)

Arm Description

Outcomes

Primary Outcome Measures

The primary outcome is safety of AAV2hAQP1 administered to the parotid gland of adult subjects with radiation-induced xerostomia
Safety will be assessed by number of adverse events occurring with treatment

Secondary Outcome Measures

Full Information

First Posted
July 23, 2019
Last Updated
April 21, 2023
Sponsor
MeiraGTx UK II Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT04043104
Brief Title
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
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
June 30, 2019 (Actual)
Primary Completion Date
March 28, 2023 (Actual)
Study Completion Date
March 28, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MeiraGTx UK II Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Radiation-Induced Parotid Gland Hypofunction, Xerostomia Due to Radiotherapy, Head and Neck Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1 x 10^11 vg/gland (single gland)
Arm Type
Experimental
Arm Title
3 x 10^10 vg/gland (both glands)
Arm Type
Experimental
Arm Title
3 x 10^11 vg/gland (single gland)
Arm Type
Experimental
Arm Title
1 x 10^11 vg/gland (both glands)
Arm Type
Experimental
Arm Title
1 x 10^12 vg/gland (single gland)
Arm Type
Experimental
Arm Title
3 x 10^11 vg/gland (both glands)
Arm Type
Experimental
Arm Title
3 x 10^12 vg/gland (single gland)
Arm Type
Experimental
Arm Title
1 x 10^12 vg/gland (both glands)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
AAV2hAQP1: 1 x 10^11 vg/gland (single gland)
Intervention Description
Intra-parotid administration of AAV2hAQP1 via Stensen's duct to a single parotid gland at a dose level of 1 x 10^11 vg/gland
Intervention Type
Drug
Intervention Name(s)
AAV2hAQP1: 3 x 10^10 vg/gland (both glands)
Intervention Description
Intra-parotid administration of AAV2hAQP1 via Stensen's duct to both parotid glands at a dose level of 3 x 10^10 vg/gland
Intervention Type
Drug
Intervention Name(s)
AAV2hAQP1: 3 x 10^11 vg/gland (single gland)
Intervention Description
Intra-parotid administration of AAV2hAQP1 of via Stensen's duct to a single parotid gland at a dose level of 3 x 10^11 vg/gland
Intervention Type
Drug
Intervention Name(s)
AAV2hAQP1: 1 x 10^11 vg/gland (both glands)
Intervention Description
intra-parotid administration of AAV2hAQP1 via Stensen's duct to both parotid glands at a dose level of 1 x 10^11 vg/gland
Intervention Type
Drug
Intervention Name(s)
AAV2hAQP1: 1 x 10^12 vg/gland (single gland)
Intervention Description
Intra-parotid administration of AAV2hAQP1 via Stensen's duct to a single parotid gland at a dose level of 1 x 10^12 vg/gland
Intervention Type
Drug
Intervention Name(s)
AAV2hAQP1: 3 x 10^11 vg/gland (both glands)
Intervention Description
Intra-parotid administration of AAV2hAQP1 via Stensen's duct to both parotid glands at a dose level of 3 x 10^11 vg/gland
Intervention Type
Drug
Intervention Name(s)
AAV2hAQP1: 3 x 10^12 vg/gland (single gland)
Intervention Description
Intra-parotid administration of AAV2hAQP1 via Stensen's duct to a single parotid gland at a dose level of 3 x 10^12 vg/gland
Intervention Type
Drug
Intervention Name(s)
AAV2hAQP1: 1 x 10^12 vg/gland (both glands)
Intervention Description
Intra-parotid administration of AAV2hAQP1 via Stensen's duct to both parotid glands at a dose level of 1 x 10^12 vg/gland
Primary Outcome Measure Information:
Title
The primary outcome is safety of AAV2hAQP1 administered to the parotid gland of adult subjects with radiation-induced xerostomia
Description
Safety will be assessed by number of adverse events occurring with treatment
Time Frame
one day to one year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female subjects ≥18 years of age. History of radiation therapy for head and neck cancer. 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 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. 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: Pregnant or lactating women or women planning to become pregnant. Any experimental therapy within 3 months before Day 1. Active infection that requires the use of intravenous antibiotics and does not resolve at least 1 week before Day 1. Uncontrolled ischemic heart disease (i.e., unstable angina, evidence of active ischemic heart disease on electrocardiogram [ECG]). History of systemic autoimmune diseases affecting the salivary glands. Use of systemic immunosuppressive medications (i.e., corticosteroids). o Note: Topical, inhaled, or intranasal corticosteroids are allowed. 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. Active infections including, Epstein-Barr virus (EBV), cytomegalovirus (CMV), hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV) infection. 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. 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. Estimated glomerular filtration rate <60 mL/min/1.73 m2 using the Modification of Diet in Renal Disease equation. Active use of tobacco products as determined by self-reporting. Allergy to iodine or shellfish, and thus unable to have sialographic evaluations. Allergy or hypersensitivity to glycopyrrolate.
Facility Information:
Facility Name
Leland Stanford Junior University
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
University of Louisville
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02184
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Atrium Health
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28209
Country
United States
Facility Name
Health Sciences North - Northeast Cancer Center
City
Sudbury
State/Province
Ontario
Country
Canada

12. IPD Sharing Statement

Learn more about this trial

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

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