A Study to Evaluate the Efficacy of Oral AKST4290 in Participants With Moderately Severe to Severe Diabetic Retinopathy (CAPRI)

Study Overview
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Brief Summary
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A Double-Masked, Placebo-Controlled Study to Evaluate the Efficacy of Oral AKST4290 in Participants with Moderately Severe to Severe Diabetic Retinopathy (CAPRI).

Detailed Description
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This study is designed to evaluate the efficacy of AKST4290 administered at a total daily dose (TDD) of 800 mg daily (400 mg twice daily [b.i.d.]) compared with placebo over a 24-week dosing period in participants with moderately severe non-proliferative diabetic retinopathy (NPDR) to severe NPDR. Participants will be enrolled and allocated to 1 of 2 treatment arms in a 2:1 randomization scheme (AKST4290: placebo). Participants will receive treatment for a total of 24 weeks with either AKST4290 800 mg daily (400 mg b.i.d.) in Arm 1 or placebo (matching tablets) in Arm 2

Official Title
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A Double-Masked, Placebo-Controlled Study to Evaluate the Efficacy of Oral AKST4290 in Participants With Moderately Severe to Severe Diabetic Retinopathy (CAPRI)

Conditions
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Diabetic Retinopathy

Intervention / Treatment
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* Drug: AKST4290
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years. Type 1 or type 2 DM. BCVA ETDRS visual acuity letter score≥ 69 letters at Screening. Moderately severe NPDR (DRSS Level 47) to severe NPDR (DRSS Level 53). Exclusion Criteria: Evidence of neovascularization (NV) (including active iris or angle NV) requiring treatment, per investigator discretion. PRP or grid laser within 1000 microns of the foveal center. Center-InvolvedI-Diabetic Macular Edema (CI-DME) on clinical examination (CI is defined as DME within 1,000 microns of the foveal center). Prior Intraocular of periocular steroid Injection Systemic anti-VEGF or pro-VEGF treatment within 4 months prior to enrollment and assignment to a randomized treatment. History of vitreoretinal surgery. History of major ocular surgery (including cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 4 months or anticipated within the next 6 months following randomization. History of DME or DR treatment with laser or intraocular injections of medication. Medical history or condition that, in the opinion of the investigator would preclude participation in the study. Clinically relevant abnormal laboratory value at Screening, including hematology, blood chemistry, or urinalysis (laboratory testing may be repeated once during the Screening phase). Malignancy for which the participant has undergone resection, radiation, or chemotherapy within the past 5 years (treated basal cell carcinoma or fully cured squamous cell carcinoma are allowed). Concurrent participation in another interventional clinical trial; prior clinical trial participants must have been off study agents for at least 30 days for small molecules, 4 months for disease modifying therapies, and 1 year for vaccine or immunotherapy trials prior to Screening.

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AKST4290<br>Subjects will receive AKST4290, 400mg twice daily, for 24 weeks | Drug: AKST4290<br>* Oral AKST4290<br>|
| Placebo Comparator: Placebo<br>Subjects will receive matching Placebo, twice daily, for 24 weeks | Drug: Placebo<br>* Oral Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Investigate the Efficacy of AKST4290 Assessed by the Improvement in the DRSS Score From Baseline. | The Diabetic Retinopathy Severity Scale (DRSS) divides DR into 13 levels ranging from the absence of retinopathy to severe retinopathy and is used to describe overall DR severity as well as the change in severity over time. Higher scores indicate more severe DR. To be eligible for the study, participants needed to have moderately severe non-proliferative DR (NPDR) (DRSS Level 47) to severe NPDR (DRSS Level 53) in one eye, and at least mild NPDR (DRSS Level 35) to mild proliferative DR (PDR) (DRSS Level 61) in the other eye at baseline. The DRSS score is derived from fundus photography (FP) and fluorescein angiography (FA) findings. The primary efficacy endpoint is the proportion of participants with a ≥ 3-step improvement from baseline on the DRSS score as compared with Week 24. | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Investigate Additional Measures of Efficacy of AKST4290 Assessed by the Improvement in the DRSS Score From Baseline. | The Diabetic Retinopathy Severity Scale (DRSS) divides DR into 13 levels ranging from the absence of retinopathy to severe retinopathy and is used to describe overall DR severity as well as the change in severity over time. Higher scores indicate more severe DR. The DRSS score is derived from fundus photography (FP) and fluorescein angiography (FA) findings. The secondary efficacy endpoint is the proportion of participants with a ≥ 2-step improvement from baseline on the DRSS score as compared with Week 24. | Baseline to Week 24 or 28 | 
| To Assess the Proportion of Participants Progressing to (or Worsening of) Center-involved Diabetic Macular Edema (CI-DME), Proliferative Diabetic Retinopathy (PDR), and/or Anterior-segment Neovascularization (ASNV). | The secondary efficacy endpoint is the proportion of participants progressing to the following vision-threatening complications that require treatment: CI-DME, PDR, and/or ASNV as assessed by spectral domain optical coherence tomography (SD-OCT), fundus photography (FP), and fluorescein angiography (FA), as appropriate. The central reading center must confirm progression to CI-DME and PDR before treatment is initiated; progression to ASNV, and subsequent treatment, does not require photo documentation. | Baseline to Week 28 | 
| To Assess the Time to Event of CI-DME, PDR, and/or ASNV Requiring Treatment. | The secondary efficacy endpoint is the time to the following vision-threatening event(s) that require treatment: CI-DME, PDR, and/or ASNV | Baseline to Week 28 | 
| To Assess the Overall Safety of AKST429 | Safety was assessed based on the number of participants who reported adverse events of mild, moderate or severe intensities. | Baseline to Week 28 | 
| To Assess the Effect of AKST4290 on Diabetic Kidney Disease | The secondary efficacy endpoint is the effect of AKST4290 on diabetic kidney disease as assessed by changes in clinical laboratory values over time (eg, estimated glomerular filtration rate [eGFR], urine albumin to creatinine ratio [UACR]). | Baseline to Week 28 | 
| To Evaluate the Changes From Baseline in the Workplace Productivity and Activity Impairment General Health (WPAI-GH) Questionnaire. | The WPAI-GH V2.0 is a 6-question survey used to assess the effects of a participant's health problems (i.e., physical or emotional problems or symptoms) on their ability to work and perform regular activities during the past seven days. The WPAI-GH questions will be analyzed as impairment percentages, in which higher percentages indicate greater impairment and less productivity. The following parameters will be calculated (multiply scores by 100 to express in percentages): Percent of work time missed due to health: Q2 divided by (Q2 plus Q4) Percent of impairment while working due to health: Q5 divided by 10 Percent of overall work impairment due to health: Q2 divided by (Q2 plus Q4) plus [(1 - (Q2 divided by (Q2 plus Q4 ))) multiplied by (Q5 divided by 10)] Percent of activity impairment due to health: Q6 divided by 10 | Baseline to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CCR3 inhibition, Diabetic Retinopathy, Oral Treatment