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

Age-Related Macular Degeneration Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05984927
• Other study ID #: NG101WA-01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• 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
• 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

Related Conditions & MeSH terms

• Age-Related Macular Degeneration
• Macular Degeneration

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