Evaluation of Kamuvudine-8 in Subjects With Geographic Atrophy

Study Overview
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Brief Summary
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This interventional study is a single-center, open label, 26-week study, designed to evaluate the safety and treatment efficacy of K8 in patients with geographic atrophy (GA) due to age-related macular degeneration (AMD). Up to 5 subjects will receive study medication. Study treatment will be administered by intravitreal injections. Participants will have 7 scheduled visits - Screening with baseline (injection), safety visit 2 days after injection, week 4, week 13 (injection), safety visit 2 days after injection, week 17, week 26. Exams will look for continuous changes in visual acuity, change in area of geographic atrophy lesions in diagnostic imaging, response measured by multifocal electroretinogram, change in reading speed, and change in microperimetry response.

Official Title
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A Non-Randomized, Open Label, Safety and Efficacy Study Evaluating Kamuvudine-8 (K8) for the Treatment of Patients With Geographic Atrophy

Conditions
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Geographic Atrophy, Age-Related Macular Degeneration

Intervention / Treatment
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* Drug: K8


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 50 or older, diagnosed with geographic atrophy (GA) due to age-related macular degeneration (AMD). Best corrected visual acuity (BCVA) 24 or greater Early Treatment of Diabetic Retinopathy Study (ETDRS) letters (approximately Snellen 20/320 or greater), in study eye. The entire geographic atrophy (GA) lesion must be completely visualized on the macula centered image and must be able to be imaged in its entirety and not contiguous with any areas of peripapillary atrophy except in such cases where there is a neck or some narrow area connecting the GA with the peripapillary atrophy, as determined by Fundus Autofluorescence (FAF) imaging at screening: Total geographic atrophy (GA) area must be ≥ 2.5 and ≤ 20.0 mm2 (1 and 8 disk areas [DA] respectively) If geographic atrophy (GA) is multifocal, at least one focal lesion must be ≥ 1.25 mm2 (0.5 DA), with the overall aggregate area of GA, as specified above. If geographic atrophy (GA) is unifocal, then the lesion must be extrafoveal. Presence of any pattern of hyperautofluorescence in the junctional zone of geographic atrophy (GA). Absence of hyperautofluorescence (i.e., pattern = none) is exclusionary. Fundus Autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT), or Fluorescein Angiography (FA) imaging of entire geographic atrophy (GA)lesion at least 6 months prior to entry. Exclusion Criteria: Females who are pregnant, nursing, planning a pregnancy or who are of childbearing potential not using a reliable method of contraception. History or current evidence of hypersensitivity to any components of the study medication or fluorescein, as assessed by the investigator. Participation in any investigational drug or device study within 30 days prior to baseline History or current evidence of a medical condition that may, in the opinion of the investigator, preclude the safe administration of study medication or affect the results of the study. Participation in any systemic experimental treatment or any other systemic investigational new drug within 6 weeks or 5 half-lives of the active ingredient (whichever is longer) prior to the start of study treatment. Clinical trials solely involving observation, over-the-counter vitamins, supplements, or diets are not exclusionary. Active ocular or periocular infections, malignancy History of major ophthalmic surgery in the past 3 months, and any ophthalmic surgery in study eye in the last 30 days History of significant ocular disease other than age-related macular degeneration (AMD) that may confound results Known hypersensitivity to study drug or any of the excipients in implant. Macular atrophy secondary to a condition other than age-related macular degeneration (AMD) History of laser therapy in the macular region. Aphakia or surgically compromised/absent posterior capsule including presence of scleral fixated lenses. Note: YAG laser posterior capsulotomy for posterior capsule opacification done at least 60 days prior to screening is not exclusionary. History of prior posterior vitrectomy. History of prior intraocular gene therapy for any indication. Uncontrolled glaucoma (defined as intraocular pressure >21mm Hg despite treatment with ocular hypotensive medications at baseline). Prior participation in another interventional clinical study or treatment for GA in either eye including topical, IVT, subretinal, suprachoroidal, periocular or oral medication or placebo within the last 6 weeks or 5 half-lives of the active ingredient (whichever is longer).

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with geographic atrophy associated with age-related macular degeneration<br>Kamuvudine-8 treatment (0.3 mg) at baseline visit and week 13 visit, in one eye of each subject, for a total of 5 subjects. Patients will be followed for 26 weeks after baseline visit injection. | Drug: K8<br>* sustained released intravitreal implants<br>* Other names: SOM-401;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Frequency of participants experiencing ocular or systemic adverse events. | Within the study period (of 26 weeks) | 
| Mean change in best-corrected visual acuity (BCVA) | best-corrected visual acuity as defined by the number of letters read on the scale set by the ETDRS (Early Treatment of Diabetic Retinopathy Study). (More letters read equates to better visual acuity) | At baseline visit and week 26 visit | 
| Mean change in low-luminance best-corrected visual acuity (ll-BCVA) | best-corrected visual acuity in low-lighting settings | At baseline visit and week 26 visit | 
| Change in size of geographic atrophy (GA) on fundus autofluorescence (FAF) | Change in total area of geographic atrophy lesions as analyzed with FAF imaging over the course of the trial | At baseline visit and week 26 visit | 
| change in size of geographic atrophy (GA) on optical coherence tomography (OCT) | Change in total area of geographic atrophy lesions as analyzed with OCT imaging | At baseline visit and week 26 visit | 
| change in size of geographic atrophy (GA) on fluorescein angiogram (FA) | Change in total area of geographic atrophy lesions as analyzed with FA imaging | At baseline visit and week 26 visit | 
| Change in multifocal electroretinograms (mfERG) response | Total response change measured by mfERG, which measures the electrical signal generated by a functionining eye processing information | At baseline visit, week 13 visit, and week 26 visit | 
| Change in microperimetry response | change in response to visual field testing with microperimetry (undilated) over the course of the study. | At baseline visit, week 13 visit, and week 26 visit | 
| Change in reading speed | Change in reading speed as measured by Radner reading chart procedure | At baseline visit, week 13 visit, and week 26 visit | 
| Discontinued subjects | Number of subjects exiting study for any reason | This will be done at every scheduled visit and any unscheduled visit, as well as when reported by participants (for 26 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in best corrected visual acuity (BCVA) over multiple time points | Change in best corrected visual acuity (BCVA) at each study visit | Day 2 visit, Week 4 visit, Week 13 visit, Week 13 + 2 Days visit, and Week 17 visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ophthalmology, K8, kamuvudine