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History of Changes for Study: NCT05984927
NG101 AAV Gene Therapy in Subjects With Wet Age-Related Macular Degeneration
Latest version (submitted April 29, 2024) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 August 2, 2023 None (earliest Version on record)
2 September 8, 2023 Recruitment Status, Study Status and Contacts/Locations
3 October 17, 2023 Study Status
4 February 28, 2024 Outcome Measures, Study Status, Contacts/Locations and Eligibility
5 April 1, 2024 Study Status and Contacts/Locations
6 April 29, 2024 Contacts/Locations and Study Status
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Study NCT05984927
Submitted Date:  August 2, 2023 (v1)

Open or close this module Study Identification
Unique Protocol ID: NG101WA-01
Brief Title: NG101 AAV Gene Therapy in Subjects With Wet Age-Related Macular Degeneration
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
Secondary IDs:
Open or close this module Study Status
Record Verification: August 2023
Overall Status: Not yet recruiting
Study Start: August 2023
Primary Completion: January 2025 [Anticipated]
Study Completion: January 2030 [Anticipated]
First Submitted: July 24, 2023
First Submitted that
Met QC Criteria:
August 2, 2023
First Posted: August 9, 2023 [Actual]
Last Update Submitted that
Met QC Criteria:
August 2, 2023
Last Update Posted: August 9, 2023 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Neuracle Genetics, Inc
Responsible Party: Sponsor
Collaborators: ORA, Inc.
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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).
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.
Open or close this module Conditions
Conditions: Age-Related Macular Degeneration
Keywords: Wet macular degeneration
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1/Phase 2
Interventional Study Model: Sequential Assignment
Dose Escalation Study with 3 dose cohorts
Number of Arms: 3
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 18 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
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 Names:
  • 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 Names:
  • 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 Names:
  • NG101
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Adverse Events
[ Time Frame: Day 0 (pre-treatment) and 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: Day 0 (pre-treatment) and from Week 24 to Week 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: Day 0, Week 12, 24, 52, and 104 ]

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

Change in concentration of expressed aflibercept protein in serum samples
4. Systemic Immunogenic Response
[ Time Frame: Day -7, Week 4, and week 12 ]

Change in AAV vector (NG101) genome copies as measured by PCR in blood samples
5. Systemic Immunogenic Response
[ Time Frame: Day -7, Week 4, week 8, week 12, week 24, week 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: At every visit from Screening through Week 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 260 ]

Change in CRT assessed with OCT
8. Best Corrected Visual Acuity (BCVA)
[ Time Frame: from Screening to Weeks 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 Week 260 ]

The cumulative number of rescue therapy injections per subject to maintain CNV control
Open or close this module Eligibility
Minimum Age: 50 Years
Maximum Age: 89 Years
Sex: All
Gender Based:
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 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:
  6. 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
  7. 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 ancillary testing
  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 severe cardiovascular, cerebrovascular, and neurodegenerative diseases, including active malignancy and immunocompromised conditions.
  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
Open or close this module Contacts/Locations
Central Contact Person: Sheila Yi
Telephone: 770-296-7301
Email: wetamd@neuraclegen.com
Central Contact Backup: Hea Reung Park
Email: wetamd@neuraclegen.com
Study Officials: Christopher D Riemann, MD
Principal Investigator
Neuracle Genetics, Inc. Medical Director
Locations: Canada, Ontario
Vitreous Retina Macula Specialists of Toronto
Toronto, Ontario, Canada, M8X 2X3
Contact:Contact: Tatjana Sukovic tatjana@vrmto.com
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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