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

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ClinicalTrials.gov Identifier: NCT05984927
Recruitment Status : Recruiting
First Posted : August 9, 2023
Last Update Posted : April 2, 2024
Sponsor:
Collaborator:
ORA, Inc.
Information provided by (Responsible Party):
Neuracle Genetics, Inc

Study Description
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Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Age-Related Macular Degeneration Genetic: NG101 AAV gene therapy Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Dose Escalation Study with 3 dose cohorts
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : September 8, 2023
Estimated Primary Completion Date : January 2025
Estimated Study Completion Date : January 2030

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: NG101 Gene Therapy Group 1
Single subretinal injection of 1x10^9 vector genomes of NG101 AAV gene therapy
 Genetic: NG101 AAV gene therapy
Sub retinal injection of NG101 (a non-replicating adeno-associated virus serotype 8 (AAV8) vector
Other Name: NG101
Experimental: NG101 Gene Therapy Group 2
Single subretinal injection of 3x10^9 vector genomes of NG101 AAV gene therapy
 Genetic: NG101 AAV gene therapy
Sub retinal injection of NG101 (a non-replicating adeno-associated virus serotype 8 (AAV8) vector
Other Name: NG101
Experimental: NG101 Gene Therapy Group 3
Single subretinal injection of 8x10^9 vector genomes of NG101 AAV gene therapy
 Genetic: NG101 AAV gene therapy
Sub retinal injection of NG101 (a non-replicating adeno-associated virus serotype 8 (AAV8) vector
Other Name: NG101


Outcome Measures
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Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. Systemic Immunogenic Response [ Time Frame: From Day -7 to Weeks 4, 12, and 104 ]
    Change in concentration of expressed aflibercept protein in serum samples

  4. 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

  5. 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

  6. 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

  7. Central Retinal Thickness (CRT) [ Time Frame: From Screening to Weeks 24, 52, 104, 156, 208, and 260 ]
    Change in CRT assessed with OCT

  8. 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

  9. 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


Eligibility Criteria
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Ages Eligible for Study:   50 Years to 89 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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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): NCT05984927


Contacts
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Contact: Sheila Yi 770-296-7301 wetamd@neuraclegen.com
Contact: Hea Reung Park wetamd@neuraclegen.com

Locations
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Canada, Ontario
Sunnybrook Ophthalmology and Vision Services Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Cindy Rutz    (416) 480-5091    Cindy.Rutz@sunnybrook.ca   
Principal Investigator: Peter Kertes, MD         
Vitreous Retina Macula Specialists of Toronto Recruiting
Toronto, Ontario, Canada, M8X 2X3
Contact: Tatjana Sukovic       tatjana@vrmto.com   
Sponsors and Collaborators
Neuracle Genetics, Inc
ORA, Inc.
Investigators
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Principal Investigator: Christopher D Riemann, MD Neuracle Genetics, Inc. Medical Director
More Information
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Responsible Party: Neuracle Genetics, Inc
ClinicalTrials.gov Identifier: NCT05984927    
Other Study ID Numbers: NG101WA-01
First Posted: August 9, 2023    Key Record Dates
Last Update Posted: April 2, 2024
Last Verified: April 2024

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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
Keywords provided by Neuracle Genetics, Inc:
Wet macular degeneration
Additional relevant MeSH terms:
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Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases