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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

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ClinicalTrials.gov Identifier: NCT04043104
Recruitment Status : Recruiting
First Posted : August 2, 2019
Last Update Posted : December 17, 2020
Sponsor:
Information provided by (Responsible Party):
MeiraGTx UK II Ltd

Tracking Information
First Submitted Date  ICMJE July 23, 2019
First Posted Date  ICMJE August 2, 2019
Last Update Posted Date December 17, 2020
Actual Study Start Date  ICMJE June 30, 2019
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 1, 2019)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Radiation-Induced Parotid Gland Hypofunction
  • Xerostomia Due to Radiotherapy
  • Head and Neck Cancer
Intervention  ICMJE 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

    • 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.
Study Arms  ICMJE
  • 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.
    Intervention: Drug: intra-parotid administration of AAV2hAQP1
  • 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.
    Intervention: Drug: intra-parotid administration of AAV2hAQP1
  • 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.
    Intervention: Drug: intra-parotid administration of AAV2hAQP1
  • 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.
    Intervention: Drug: intra-parotid administration of AAV2hAQP1
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 12, 2020)
30
Original Actual Enrollment  ICMJE
 (submitted: August 1, 2019)
15
Estimated Study Completion Date  ICMJE May 2022
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: MeiraGTx Advocacy 646-860-7982 aquaxstudy@meiragtx.com
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04043104
Other Study ID Numbers  ICMJE MGT016
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party MeiraGTx UK II Ltd
Study Sponsor  ICMJE MeiraGTx UK II Ltd
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account MeiraGTx UK II Ltd
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP