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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05984927
Other study ID # NG101WA-01
Secondary ID
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date September 8, 2023
Est. completion date January 2030

Study information

Verified date April 2024
Source Neuracle Genetics, Inc
Contact Sheila Yi
Phone 770-296-7301
Email wetamd@neuraclegen.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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).


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 18
Est. completion date January 2030
Est. primary completion date January 2025
Accepts healthy volunteers No
Gender All
Age group 50 Years to 89 Years
Eligibility 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 Design


Related Conditions & MeSH terms


Intervention

Genetic:
NG101 AAV gene therapy
Sub retinal injection of NG101 (a non-replicating adeno-associated virus serotype 8 (AAV8) vector

Locations

Country Name City State
Canada Sunnybrook Ophthalmology and Vision Services Toronto Ontario
Canada Vitreous Retina Macula Specialists of Toronto Toronto Ontario
Canada Vancouver Coastal Health Research Institute Vancouver British Columbia

Sponsors (2)

Lead Sponsor Collaborator
Neuracle Genetics, Inc ORA, Inc.

Country where clinical trial is conducted

Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary Adverse Events Incidence and severity of ocular and non-ocular adverse events (AEs) for each cohort From Day 0 (pre-treatment) through Week 24
Secondary Ocular and Non -Ocular Adverse Events after week 24 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
Secondary Systemic Immunogenic Response Change in concentration of expressed aflibercept protein in vitreous samples From Day 0 to Weeks 12, 24, 52, and 104
Secondary Systemic Immunogenic Response Change in concentration of expressed aflibercept protein in serum samples From Day -7 to Weeks 4, 12, and 104
Secondary Systemic Immunogenic Response 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
Secondary Systemic Immunogenic Response 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
Secondary Signs of CNV Activity Change of 1 or more signs of CNV activity assessed by Optical coherence tomography From Day -30 to Weeks 8, 24, 52, and 104
Secondary Central Retinal Thickness (CRT) Change in CRT assessed with OCT From Screening to Weeks 24, 52, 104, 156, 208, and 260
Secondary Best Corrected Visual Acuity (BCVA) Change in BCVA assessed with Early Treatment Diabetic Retinopathy Study (ETDRS) scale From Screening to Weeks24, 52, 104, 156, 208 and 260
Secondary Cumulative Number of Rescue Therapy Injections The cumulative number of rescue therapy injections per subject to maintain CNV control From Week 24 to Weeks 52, 104, 156, 208, and 260
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