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

• ClinicalTrials.gov Identifier: NCT05984927
• Recruitment Status: Recruiting
• First Posted: August 9, 2023
• Last Update Posted: May 1, 2024
• Sponsor: Neuracle Genetics, Inc
• Collaborator: ORA, Inc.
• Information provided by (Responsible Party): Neuracle Genetics, Inc

Tracking Information

• First Submitted Date: July 24, 2023
• First Posted Date: August 9, 2023
• Last Update Posted Date: May 1, 2024
• Actual Study Start Date: September 8, 2023
• Estimated Primary Completion Date: January 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 28, 2024)

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

Original Primary Outcome Measures (submitted: August 2, 2023)

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

Current Secondary Outcome Measures (submitted: February 28, 2024)

• 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
• 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
• Systemic Immunogenic Response [ Time Frame: From Day -7 to Weeks 4, 12, and 104 ]
  Change in concentration of expressed aflibercept protein in serum samples
• 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
• 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
• 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
• Central Retinal Thickness (CRT) [ Time Frame: From Screening to Weeks 24, 52, 104, 156, 208, and 260 ]
  Change in CRT assessed with OCT
• 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
• 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

Original Secondary Outcome Measures (submitted: August 2, 2023)

• 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
• Systemic Immunogenic Response [ Time Frame: Day 0, Week 12, 24, 52, and 104 ]
  Change in concentration of expressed aflibercept protein in vitreous samples
• Systemic Immunogenic Response [ Time Frame: Day -7 Weeks 4, 12, and 104 ]
  Change in concentration of expressed aflibercept protein in serum samples
• 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
• 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
• 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
• Central Retinal Thickness (CRT) [ Time Frame: from Screening to Weeks 260 ]
  Change in CRT assessed with OCT
• Best Corrected Visual Acuity (BCVA) [ Time Frame: from Screening to Weeks 260 ]
  Change in BCVA assessed with Early Treatment Diabetic Retinopathy Study (ETDRS) scale
• 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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Dose Escalation Study with 3 dose cohorts

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Age-Related Macular Degeneration

Intervention

Genetic: NG101 AAV gene therapy

Sub retinal injection of NG101 (a non-replicating adeno-associated virus serotype 8 (AAV8) vector

Other Name: NG101

Study Arms

• Experimental: NG101 Gene Therapy Group 1
  Single subretinal injection of 1x10^9 vector genomes of NG101 AAV gene therapy
  Intervention: Genetic: NG101 AAV gene therapy
• Experimental: NG101 Gene Therapy Group 2
  Single subretinal injection of 3x10^9 vector genomes of NG101 AAV gene therapy
  Intervention: Genetic: NG101 AAV gene therapy
• Experimental: NG101 Gene Therapy Group 3
  Single subretinal injection of 8x10^9 vector genomes of NG101 AAV gene therapy
  Intervention: Genetic: NG101 AAV gene therapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 2, 2023): 18
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 2030
• Estimated Primary Completion Date: January 2025 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years to 89 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Sheila Yi; 770-296-7301; wetamd@neuraclegen.com

Contact: Hea Reung Park; wetamd@neuraclegen.com

• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT05984927
• Other Study ID Numbers: NG101WA-01
• 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
• Product Manufactured in and Exported from the U.S.: Yes

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Neuracle Genetics, Inc
• Original Responsible Party: Same as current
• Current Study Sponsor: Neuracle Genetics, Inc
• Original Study Sponsor: Same as current
• Collaborators: ORA, Inc.

Investigators

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

• PRS Account: Neuracle Genetics, Inc
• Verification Date: April 2024