Safety and Effect of Intravitreal Injection of a Derivative of Nucleoside Reverse Transcriptase Inhibitor in Subjects with Diabetic Macular Edema

A Non-randomized, Open Label, Safety and Efficacy Study Evaluating a Single Dose of Kamuvudine-8 (K8) for the Treatment of Patients with Diabetic Macular Edema

This study is designed to assess the safety and initial evidence of efficacy of the novel compound SOM-401 (K8), a derivative of a nucleoside reverse transcriptase inhibitor, in subjects with untreated, clinically significant, diabetic macular edema (DME).

Study Overview

• Status: Completed
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Drug: K8

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40506
      • University of Kentucky

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 years or older
• BCVA of ≥ 24 and ≤ 73 letters (20/40 or worse but at least 20/320) by an ETDRS chart. BCVA of the non-study eye must be no worse than 20/400)
• Diagnosis of diabetes mellitus, type 1 or 2 with non-proliferative or non-high risk proliferative diabetic retinopathy.
• DME based on investigator's clinical evaluation and demonstrated on fundus photographs, fluorescein angiograms, and spectral domain-optical coherence tomography (SD-OCT)
• Mean foveal thickness of at least 300 µm by SD-OCT
• Ability and willingness to comply with the treatment and follow-up procedures
• Ability to understand and sign the informed consent form
• Intraocular pressure of ≤ 21 on 2 or less IOP lowering medications

Exclusion Criteria:

• Pregnant patients, currently lactating patients, or females of childbearing potential (unless using reliable contraception such as double barrier, surgical sterilization, oral contraceptives, intrauterine device (IUD), etc.)
• Allergy or hypersensitivity (known or suspected) to fluorescein or any component of the investigational product or delivery system
• Any ocular surgery in the study eye within 12 weeks of screening
• Any history of vitrectomy in the study eye
• Aphakia in the study eye
• Presence of severe foveal ischemia, defined as foveal avascular zone (FAZ) of >1.5 mm2 on OCT-Angiography
• Prior intraocular or periocular treatment for DME
• Macular laser for the treatment of diabetic macular edema within 12 weeks of screening
• Any change in systemic steroidal therapy within 3 months of screening
• Retinal or choroidal neovascularization due to ocular conditions other than diabetic retinopathy
• History or presence of viral disease of the cornea or conjunctiva
• History or presence of any disease or condition that in the investigator's opinion would preclude study treatment or follow-up or that in the opinion of the investigator would render them as unlikely to benefit from study treatment.
• Any lens or corneal opacity which impairs visualization of the posterior pole
• Participation in another clinical trial within 12 weeks before the screening visit or during the study
• Expectation that subject will be moving away from the area of the clinical treatment center without the ability to return for visits within the study period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with Diabetic Macular Edema	Drug: K8; Subjects will have the treatment administered intravitreally (one eye only) using an injector system on a 24-gauge needle to deliver a cylindrical, 3 mm long, drug eluting pellet containing 300 µg of K8. Participants will be followed for 168 days (24 weeks).; Other Names: SOM-401

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in central subfield thickness	Central subfield thickness (CST) measured on spectral domain-optical coherence tomography (SD-OCT)	At week 4 (change as measured from baseline)
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 week 4 (change as measured from baseline)
Adverse Events	Frequency of participants experiencing ocular or systemic adverse events.	Within the study period (of 24 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resolution of macular edema	Frequency of participants experiencing resolution of macular edema	24 weeks (at 2, 4, 8, 12, 16, and 24 weeks)
Clinically significant change in visual acuity	Frequency of participants experiencing clinically significant change.	24 weeks (at 2, 4, 8, 12, 16, and 24 weeks)
Change in score on the ETDRS Multi-Step Scale of Diabetic Retinopathy	The Early Treatment Diabetic Retinopathy Study (ETDRS DRSS) was developed to categorize the severity of diabetic retinopathy based on several fundus photographic characteristics. There are 13 levels in the original ETDRS scale, and a severity step or level increase is associated with an increased risk of retinopathy progression. The scale goes from 10 to 85, with higher scores being worse.	24 weeks
Visual acuity	The proportion of subjects who have an change from baseline of ETDRS letters read of ≥ 5 letters, ≥ 10 letters or ≥ 15 letters of visual acuity.	24 weeks (at 2, 4, 8, 12, 16, and 24 weeks)
Change in retinal thickening	Total area in disc diameters of retinal thickening of the lesion involving the foveal center, based on fundus imaging.	24 weeks (at 2, 4, 8, 12, 16, and 24 weeks)
Change in hard exudates	Total area in disc diameters of hard exudates in the lesion involving the macula, based on fundus imaging.	24 weeks (at 2, 4, 8, 12, 16, and 24 weeks)
Change in foveal avascular zone.	Foveal avascular zone size as determined using OCT-Angiography	24 weeks (at 2, 4, 8, 12, 16, and 24 weeks)
Proportion of subjects requiring rescue treatment	Proportion of subjects requiring rescue treatment	24 weeks (at 2, 4, 8, 12, 16, and 24 weeks)
Proportion of subjects requiring vitrectomy	Proportion of subjects requiring vitrectomy	24 weeks (at 2, 4, 8, 12, 16, and 24 weeks)
Mean change in central subfield thickness at other study timepoints	Central subfield thickness (CST) measured on spectral domain-optical coherence tomography (SD-OCT)	24 weeks (at 2, 8, 12, 16, and 24 weeks)
Mean change in best-corrected visual acuity (BCVA) at other study timepoints	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)	24 weeks (at 2, 4, 8, 12, 16, and 24 weeks)

Collaborators and Investigators

• Sponsor: Michelle Abou-Jaoude
• Collaborators: Inflammasome Therapeutics
• Investigators: Principal Investigator: Michelle Abou-Jaoude, MD, University of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2024
• Primary Completion (Actual): June 20, 2024
• Study Completion (Actual): June 20, 2024

Study Registration Dates

• First Submitted: December 23, 2022
• First Submitted That Met QC Criteria: January 22, 2023
• First Posted (Actual): January 26, 2023

Study Record Updates

• Last Update Posted (Estimated): November 1, 2024
• Last Update Submitted That Met QC Criteria: October 29, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: diabetes; kamuvudine; K8; SOM-401
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Retinal Degeneration; Macular Degeneration; Edema; Macular Edema; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Zidovudine
• Other Study ID Numbers: 79071

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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.: No