Clinical trial NCT06164587: Evaluation of Kamuvudine-8 in Subjects With Geographic Atrophy
Official title: A Non-Randomized, Open Label, Safety and Efficacy Study Evaluating Kamuvudine-8 (K8) for the Treatment of Patients With Geographic Atrophy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Geographic Atrophy
Age-Related Macular Degeneration
Keywords: ophthalmology
K8
kamuvudine
Lead sponsor: University of Kentucky
Sponsor class: OTHER
Collaborators: name: Inflammasome Therapeutics
First posted: 2023-12-11
Enrollment: 30
Sex: ALL
Minimum age (years): 50
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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. Number of participants has been expanded to 30.

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Adverse Events
timeFrame: Within the study period (of 26 weeks)
measure: Mean change in best-corrected visual acuity (BCVA)
timeFrame: At baseline visit, week 13 visit, and week 26 visit
measure: Mean change in low-luminance best-corrected visual acuity (ll-BCVA)
timeFrame: At baseline visit, week 13 visit, and week 26 visit
measure: Change in size of geographic atrophy (GA) on fundus autofluorescence (FAF)
timeFrame: At baseline visit, week 13 visit, and week 26 visit
measure: change in size of geographic atrophy (GA) on optical coherence tomography (OCT)
timeFrame: At baseline visit, week 13 visit, and week 26 visit
measure: change in size of geographic atrophy (GA) on fluorescein angiogram (FA)
timeFrame: At baseline visit, week 13 visit, and week 26 visit
measure: Change in multifocal electroretinograms (mfERG) response
timeFrame: At baseline visit, week 13 visit, and week 26 visit
measure: Change in microperimetry response
timeFrame: At baseline visit, week 13 visit, and week 26 visit
measure: Change in reading speed
timeFrame: At baseline visit, week 13 visit, and week 26 visit
measure: Discontinued subjects
timeFrame: This will be done at every scheduled visit and any unscheduled visit, as well as when reported by participants (for 26 weeks)
Secondary outcomes:
measure: Change in best corrected visual acuity (BCVA) over multiple time points
timeFrame: Day 2 visit, Week 4 visit, Week 13 visit, Week 13 + 2 Days visit, and Week 17 visit
Other outcomes:
Locations:
city: Lexington
country: United States
facility: University of Kentucky Advanced Eye Care
state: Kentucky
city: Portland
country: United States
facility: The Maine Eye Center
state: Maine
city: Eugene
country: United States
facility: Oregon Eye Consultants, Cascade Medical Research
state: Oregon
city: Sioux Falls
country: United States
facility: Ophthalmology LTD
state: South Dakota
city: Roanoke
country: United States
facility: Vistar Eye Center
state: Virginia
Study officials:
affiliation: University of Kentucky
name: Michelle Abou-Jaoude, MD
role: PRINCIPAL_INVESTIGATOR
References: