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A Phase 1/2 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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ClinicalTrials.gov Identifier: NCT04043104
Recruitment Status : Recruiting
First Posted : August 2, 2019
Last Update Posted : September 25, 2019
Sponsor:
Information provided by (Responsible Party):
MeiraGTx UK II Ltd

Brief 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.


Condition or disease Intervention/treatment Phase
Radiation-Induced Parotid Gland Hypofunction Xerostomia Due to Radiotherapy Head and Neck Cancer Drug: intra-parotid administration of AAV2hAQP1 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 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
Actual Study Start Date : June 30, 2019
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : May 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Dry Mouth

Arm Intervention/treatment
Experimental: 1 x 1011 vg/mL
The starting dose will be at a titer of 1 x 1011 vg/mL. The viral titer used to dose each consecutive cohort of subjects will be increased as follows: 3 x 1011 vg/mL, 1 x 1012 vg/mL, 3 x 1012 vg/mL, and 6 x 1012 vg/mL. If 2 subjects experience a DLT at the 1 x 1011 vg/mL dose level (Dose Group 1; see Table 2), then a lower dose of 3 x 1010 vg/mL may be studied. Depending upon the occurrence of a protocol-defined toxicity, an additional 1-3 subjects may be enrolled into a dose group.
Drug: intra-parotid administration of AAV2hAQP1

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. Dose levels:

  • 1 x 1011 vg/mL*
  • 3 x 1011 vg/mL
  • 1 x 1012 vg/mL
  • 3 x 1012 vg/mL
  • 6 x 1012 vg/mL

    • If 2 subjects experience a dose-limiting toxicity at the 1 x 1011 vg/mL dose level (Dose Group 1), then a lower dose of 3 x 1010 vg/mL may be studied. The total volume to be administered is subject specific, based on the subject's parotid gland volume.

Experimental: 3 x 1011 vg/mL
The starting dose will be at a titer of 1 x 1011 vg/mL. The viral titer used to dose each consecutive cohort of subjects will be increased as follows: 3 x 1011 vg/mL, 1 x 1012 vg/mL, 3 x 1012 vg/mL, and 6 x 1012 vg/mL. If 2 subjects experience a DLT at the 1 x 1011 vg/mL dose level (Dose Group 1; see Table 2), then a lower dose of 3 x 1010 vg/mL may be studied. Depending upon the occurrence of a protocol-defined toxicity, an additional 1-3 subjects may be enrolled into a dose group.
Drug: intra-parotid administration of AAV2hAQP1

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. Dose levels:

  • 1 x 1011 vg/mL*
  • 3 x 1011 vg/mL
  • 1 x 1012 vg/mL
  • 3 x 1012 vg/mL
  • 6 x 1012 vg/mL

    • If 2 subjects experience a dose-limiting toxicity at the 1 x 1011 vg/mL dose level (Dose Group 1), then a lower dose of 3 x 1010 vg/mL may be studied. The total volume to be administered is subject specific, based on the subject's parotid gland volume.

Experimental: 1 x 1012 vg/mL
The starting dose will be at a titer of 1 x 1011 vg/mL. The viral titer used to dose each consecutive cohort of subjects will be increased as follows: 3 x 1011 vg/mL, 1 x 1012 vg/mL, 3 x 1012 vg/mL, and 6 x 1012 vg/mL. If 2 subjects experience a DLT at the 1 x 1011 vg/mL dose level (Dose Group 1; see Table 2), then a lower dose of 3 x 1010 vg/mL may be studied. Depending upon the occurrence of a protocol-defined toxicity, an additional 1-3 subjects may be enrolled into a dose group.
Drug: intra-parotid administration of AAV2hAQP1

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. Dose levels:

  • 1 x 1011 vg/mL*
  • 3 x 1011 vg/mL
  • 1 x 1012 vg/mL
  • 3 x 1012 vg/mL
  • 6 x 1012 vg/mL

    • If 2 subjects experience a dose-limiting toxicity at the 1 x 1011 vg/mL dose level (Dose Group 1), then a lower dose of 3 x 1010 vg/mL may be studied. The total volume to be administered is subject specific, based on the subject's parotid gland volume.

Experimental: 3 x 1012 vg/mL
The starting dose will be at a titer of 1 x 1011 vg/mL. The viral titer used to dose each consecutive cohort of subjects will be increased as follows: 3 x 1011 vg/mL, 1 x 1012 vg/mL, 3 x 1012 vg/mL, and 6 x 1012 vg/mL. If 2 subjects experience a DLT at the 1 x 1011 vg/mL dose level (Dose Group 1; see Table 2), then a lower dose of 3 x 1010 vg/mL may be studied. Depending upon the occurrence of a protocol-defined toxicity, an additional 1-3 subjects may be enrolled into a dose group.
Drug: intra-parotid administration of AAV2hAQP1

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. Dose levels:

  • 1 x 1011 vg/mL*
  • 3 x 1011 vg/mL
  • 1 x 1012 vg/mL
  • 3 x 1012 vg/mL
  • 6 x 1012 vg/mL

    • If 2 subjects experience a dose-limiting toxicity at the 1 x 1011 vg/mL dose level (Dose Group 1), then a lower dose of 3 x 1010 vg/mL may be studied. The total volume to be administered is subject specific, based on the subject's parotid gland volume.

Experimental: 6 x 1012 vg/mL
The starting dose will be at a titer of 1 x 1011 vg/mL. The viral titer used to dose each consecutive cohort of subjects will be increased as follows: 3 x 1011 vg/mL, 1 x 1012 vg/mL, 3 x 1012 vg/mL, and 6 x 1012 vg/mL. If 2 subjects experience a DLT at the 1 x 1011 vg/mL dose level (Dose Group 1; see Table 2), then a lower dose of 3 x 1010 vg/mL may be studied. Depending upon the occurrence of a protocol-defined toxicity, an additional 1-3 subjects may be enrolled into a dose group.
Drug: intra-parotid administration of AAV2hAQP1

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. Dose levels:

  • 1 x 1011 vg/mL*
  • 3 x 1011 vg/mL
  • 1 x 1012 vg/mL
  • 3 x 1012 vg/mL
  • 6 x 1012 vg/mL

    • If 2 subjects experience a dose-limiting toxicity at the 1 x 1011 vg/mL dose level (Dose Group 1), then a lower dose of 3 x 1010 vg/mL may be studied. The total volume to be administered is subject specific, based on the subject's parotid gland volume.




Primary Outcome Measures :
  1. The primary outcome is safety of AAV2hAQP1 administered to the parotid gland of adult subjects with radiation-induced xerostomia [ Time Frame: one day to one year ]
    Safety will be assessed by number of adverse events occurring with treatment



Information from the National Library of Medicine

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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female subjects ≥18 years of age.
  2. History of radiation therapy for head and neck cancer.
  3. MD Anderson Symptom Inventory-Head and Neck module-dry mouth score >6.
  4. 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.
  5. 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.
  6. 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.
  7. 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.

Information from the National Library of Medicine

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): NCT04043104


Contacts
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Contact: Melanie Von Schimmelmann 646-440-9133 melanie@meiragtx.com

Locations
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United States, Kentucky
University of Louisville Not yet recruiting
Louisville, Kentucky, United States, 40202
United States, Massachusetts
Brigham and Women's Hospital Not yet recruiting
Boston, Massachusetts, United States, 02184
United States, New York
Memorial Sloan Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
United States, North Carolina
Atrium Health Recruiting
Charlotte, North Carolina, United States, 28209
Contact: Michael Brennan    704-355-4197    mike.brennan@atriumhealth.org   
Canada, Ontario
Health Sciences North - Northeast Cancer Center Not yet recruiting
Sudbury, Ontario, Canada
Sponsors and Collaborators
MeiraGTx UK II Ltd

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Responsible Party: MeiraGTx UK II Ltd
ClinicalTrials.gov Identifier: NCT04043104     History of Changes
Other Study ID Numbers: MGT016
First Posted: August 2, 2019    Key Record Dates
Last Update Posted: September 25, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Xerostomia
Salivary Gland Diseases
Mouth Diseases
Stomatognathic Diseases