NG101 AAV Gene Therapy in Subjects With Wet Age-Related Macular Degeneration

April 29, 2024 updated by: Neuracle Genetics, Inc

A Phase 1/2a Open-label Study to Evaluate Safety, Tolerability and Preliminary Efficacy of NG101 AAV Gene Therapy in Subjects With Wet Age-Related Macular Degeneration

This study will evaluate the safety, tolerability, and preliminary efficacy of NG101 AAV gene therapy administered by subretinal injections into a single selected eye as a single selected dose for patients with wet age-related macular degeneration (wAMD).

Study Overview

Status

Recruiting

Intervention / Treatment

Detailed Description

This is a Phase 1/2a, multicenter, open-label, dose escalation study to evaluate the safety, tolerability, and preliminary efficacy of NG101 AAV gene therapy, administered by subretinal injection in patients with active wAMD symptoms. The study will be conducted at approximately 6 sites in Canada and the USA.

Study Type

Interventional

Enrollment (Estimated)

18

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 3N9
        • Recruiting
        • Vancouver Coastal Health Research Institute
        • Contact:
        • Contact:
        • Principal Investigator:
          • Eduardo Navajas, MD
    • Ontario
      • Toronto, Ontario, Canada, M8X 2X3
        • Recruiting
        • Vitreous Retina Macula Specialists of Toronto
        • Principal Investigator:
          • Netan Choudhry, MD
        • Contact:
      • Toronto, Ontario, Canada, M4N 3M5
        • Recruiting
        • Sunnybrook Ophthalmology and Vision Services
        • Contact:
        • Principal Investigator:
          • Peter Kertes, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Subjects ≥ 50 and ≤ 89 years of age with a diagnosis of active subfoveal CNV secondary to wAMD in the Study Eye
  2. BCVA between 20/63 and 20/400 in the Study Eye, with BCVA decrement primarily attributable to wAMD
  3. Administration of at least 3 anti-VEGF injections in potential study eye in the past 6 months, the most recent of which was within 2 months prior to Screening.
  4. Must be pseudo phakic (status post cataract surgery) in the Study Eye
  5. Female subjects must be either: (1) of non-childbearing potential; or (2) of childbearing potential and using an acceptable method of birth control with a negative pregnancy test. Male subjects agree to refrain from sperm donations and practice contraception to avoid any pregnancy for 3 months after.
  6. Normal blood pressure (BP) and heart rate (HR), or near normal BP and HR not considered clinically significant (NCS) by the Investigator at the Screening Visits (Day -30 to Day -8 and Day -7) after 10 minutes resting in supine or sitting position
  7. Willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to the performance of any study-related procedures
  8. Willingness and ability to comply with schedule for follow-up visits and postoperative evaluations

Exclusion Criteria:

  1. CNV or macular edema in the Study Eye secondary to any causes other than AMD
  2. Any condition preventing visual acuity improvement in the Study Eye, e.g., fibrosis, atrophy, or retinal pigment epithelial tear in the center of the macula
  3. Any ophthalmic condition that precludes adequate ophthalmic examination or requires treatment
  4. Retinal detachment or history of retinal detachment in the Study Eye
  5. Active uncontrolled glaucoma with intraocular pressure (IOP) ≥ 30 mmHg despite treatment with more than 2 glaucoma medications, advanced glaucoma with cup-to-disc ratio of ≥ 0.9, visual field defects secondary to glaucoma that involve the macula, and/or optic atrophy from glaucoma
  6. History of intravitreal therapy in the Study Eye, such as intravitreal steroid injection or an investigational product, other than anti-VEGF therapy, in the 6 months prior to Screening
  7. History of vitrectomy, trabeculectomy, glaucoma tube-shunt procedure, minimally invasive glaucoma surgery (MIGS) device, or other filtration surgery in the Study Eye
  8. Any prior treatment with photodynamic therapy or retinal laser for the treatment of wAMD
  9. Any prior therapeutic radiation in the region of the Study Eye such as whole brain radiation, proton beam radiation, gamma knife treatment, or plaque brachytherapy
  10. Any previous intraocular or refractive surgery on the Study Eye within 6 months
  11. Any previous gene therapy in the Study Eye
  12. Presence of an ocular implant in the Study Eye at Screening, excluding intraocular lens and custom flex iris prosthesis
  13. Any diabetic retinopathy or other retinal vascular disease including retinal vein occlusion, retinal artery occlusion, retinal arterial macro aneurysm, ocular ischemic syndrome, retinal vasculitis, vitritis, posterior uveitis
  14. Any medically uncontrolled diabetes, defined as HbA1C > 8.0
  15. History of ocular melanoma
  16. History of any known inherited retinal disease
  17. Currently taking any anticoagulant therapy, which is deemed medically necessary and cannot be permanently stopped at least 2 weeks prior to NG101 injection, excluding prophylactic low-dose aspirin therapy
  18. Any underlying systemic diseases as unstable or severe cardiovascular, cerebrovascular, dementia or neurodegenerative diseases of a level that prevents adequate evaluation of the subject during the study, active malignancy or currently undergoing treatment for active malignancy at Screening or a history of malignancy that precludes completion of this 260 week study, and immunocompromised conditions and/or need for immunosuppressive therapy.
  19. Active hepatitis B or C
  20. History of human immunodeficiency virus (HIV), active tuberculosis, and/or syphilis
  21. Any significant illness that would preclude study compliance and follow-up
  22. Subjects who, in the Investigator's opinion, lack the mental capacity to provide written informed consent for study participation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: NG101 Gene Therapy Group 1
Single subretinal injection of 1x10^9 vector genomes of NG101 AAV gene therapy
Sub retinal injection of NG101 (a non-replicating adeno-associated virus serotype 8 (AAV8) vector
Other Names:
  • NG101
Experimental: NG101 Gene Therapy Group 2
Single subretinal injection of 3x10^9 vector genomes of NG101 AAV gene therapy
Sub retinal injection of NG101 (a non-replicating adeno-associated virus serotype 8 (AAV8) vector
Other Names:
  • NG101
Experimental: NG101 Gene Therapy Group 3
Single subretinal injection of 8x10^9 vector genomes of NG101 AAV gene therapy
Sub retinal injection of NG101 (a non-replicating adeno-associated virus serotype 8 (AAV8) vector
Other Names:
  • NG101

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Events
Time Frame: From Day 0 (pre-treatment) through Week 24
Incidence and severity of ocular and non-ocular adverse events (AEs) for each cohort
From Day 0 (pre-treatment) through Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ocular and Non -Ocular Adverse Events after week 24
Time Frame: From Day 0 (pre-treatment) and through Weeks 52, 104, 156, 208 and 260
Incidence and severity of ocular and non-ocular AEs after Week 24 to Week 260 for each cohort
From Day 0 (pre-treatment) and through Weeks 52, 104, 156, 208 and 260
Systemic Immunogenic Response
Time Frame: From Day 0 to Weeks 12, 24, 52, and 104
Change in concentration of expressed aflibercept protein in vitreous samples
From Day 0 to Weeks 12, 24, 52, and 104
Systemic Immunogenic Response
Time Frame: From Day -7 to Weeks 4, 12, and 104
Change in concentration of expressed aflibercept protein in serum samples
From Day -7 to Weeks 4, 12, and 104
Systemic Immunogenic Response
Time Frame: From Day -7 to Week 4, and week 12 if week 4 result was positive
Change in AAV vector (NG101) genome copies as measured by qPCR in blood samples
From Day -7 to Week 4, and week 12 if week 4 result was positive
Systemic Immunogenic Response
Time Frame: From Day -7 to Weeks 4, 8, 12, 24, 52, and week 104
Change in concentration of Anti-NG101 Transgene protein antibodies, Anti-AAV8 Neutralizing antibodies, and Anti-AAV8 Antibodies in serum samples
From Day -7 to Weeks 4, 8, 12, 24, 52, and week 104
Signs of CNV Activity
Time Frame: From Day -30 to Weeks 8, 24, 52, and 104
Change of 1 or more signs of CNV activity assessed by Optical coherence tomography
From Day -30 to Weeks 8, 24, 52, and 104
Central Retinal Thickness (CRT)
Time Frame: From Screening to Weeks 24, 52, 104, 156, 208, and 260
Change in CRT assessed with OCT
From Screening to Weeks 24, 52, 104, 156, 208, and 260
Best Corrected Visual Acuity (BCVA)
Time Frame: From Screening to Weeks24, 52, 104, 156, 208 and 260
Change in BCVA assessed with Early Treatment Diabetic Retinopathy Study (ETDRS) scale
From Screening to Weeks24, 52, 104, 156, 208 and 260
Cumulative Number of Rescue Therapy Injections
Time Frame: From Week 24 to Weeks 52, 104, 156, 208, and 260
The cumulative number of rescue therapy injections per subject to maintain CNV control
From Week 24 to Weeks 52, 104, 156, 208, and 260

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Principal Investigator: Christopher D Riemann, MD, Neuracle Genetics, Inc. Medical Director

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 8, 2023

Primary Completion (Estimated)

January 1, 2025

Study Completion (Estimated)

January 1, 2030

Study Registration Dates

First Submitted

July 24, 2023

First Submitted That Met QC Criteria

August 2, 2023

First Posted (Actual)

August 9, 2023

Study Record Updates

Last Update Posted (Actual)

May 1, 2024

Last Update Submitted That Met QC Criteria

April 29, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Other Study ID Numbers

  • NG101WA-01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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