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Study terminated due to safety findings in other AKST4290 studies
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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).
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AKST4290 | Experimental | Subjects will receive AKST4290, 400mg twice daily, for 24 weeks |
|
| Placebo | Placebo Comparator | Subjects will receive matching Placebo, twice daily, for 24 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AKST4290 | Drug | Oral AKST4290 |
| |
| Placebo |
| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Alkahest Medical Monitor | Alkahest, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Site 132 | Phoenix | Arizona | 85021 | United States | ||
| Site 136 |
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The study was terminated early by the Sponsor. At the time of discontinuation, three participants were enrolled and none completed the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | AKST4290 | Subjects will receive AKST4290, 400mg twice daily, for 24 weeks AKST4290: Oral AKST4290 |
| FG001 | Placebo | Subjects will receive matching Placebo, twice daily, for 24 weeks Placebo: Oral Placebo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 19, 2021 | Feb 16, 2023 |
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| Drug |
Oral Placebo |
|
| 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):
| Baseline to Week 24 |
| Phoenix |
| Arizona |
| 85053 |
| United States |
| Site 123 | Glendale | California | 91203 | United States |
| Site 121 | Huntington Beach | California | 92647 | United States |
| Site 116 | Clearwater | Florida | 33761 | United States |
| Site 117 | Sarasota | Florida | 34239 | United States |
| Site 118 | Winter Haven | Florida | 33880 | United States |
| Site 120 | Oak Forest | Illinois | 60452 | United States |
| Site 133 | Beaufort | South Carolina | 29902 | United States |
| Site 127 | Ladson | South Carolina | 29456 | United States |
| Site 122 | Arlington | Texas | 76012 | United States |
| Site 130 | Bellaire | Texas | 77401 | United States |
| Site 126 | Harlingen | Texas | 78550 | United States |
| Site 134 | Houston | Texas | 77025 | United States |
| Site 129 | Katy | Texas | 77494 | United States |
| Site 128 | San Antonio | Texas | 78240 | United States |
| Site 125 | Salt Lake City | Utah | 84107 | United States |
| COMPLETED |
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| NOT COMPLETED |
|
|
The study was terminated by the Sponsor. Only 3 participants were enrolled in this study. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.
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| ID | Title | Description |
|---|---|---|
| BG000 | AKST4290 | Subjects will receive AKST4290, 400mg twice daily, for 24 weeks AKST4290: Oral AKST4290 |
| BG001 | Placebo | Subjects will receive matching Placebo, twice daily, for 24 weeks Placebo: Oral Placebo |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical |
| ||||||||||||||||||||||||||||||
| Sex: Female, Male |
| ||||||||||||||||||||||||||||||
| Ethnicity (NIH/OMB) |
| ||||||||||||||||||||||||||||||
| Race (NIH/OMB) |
| ||||||||||||||||||||||||||||||
| Diabetes Mellitus Type |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The study was terminated by the Sponsor. Only 3 participants were enrolled in this study. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality. | Posted | Baseline to Week 24 |
|
| ||||||||||||||||||||||
| Secondary | 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. | The study was terminated by the Sponsor. Only 3 participants were enrolled in this study. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality. | Posted | Baseline to Week 24 or 28 |
|
| ||||||||||||||||||||||
| Secondary | 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. | The study was terminated by the Sponsor. Only 3 participants were enrolled in this study. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality. | Posted | Baseline to Week 28 |
|
| ||||||||||||||||||||||
| Secondary | 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 | The study was terminated by the Sponsor. Only 3 participants were enrolled in this study. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality. | Posted | Baseline to Week 28 |
|
| ||||||||||||||||||||||
| Secondary | 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. | The study was terminated early by the Sponsor. At the time of discontinuation, three participants were enrolled, and all participants were allocated to randomized treatment with AKST4290. | Posted | Count of Participants | Participants | Baseline to Week 28 |
|
| ||||||||||||||||||||
| Secondary | 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]). | The study was terminated by the Sponsor. Only 3 participants were enrolled in this study. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality. | Posted | Baseline to Week 28 |
|
| ||||||||||||||||||||||
| Secondary | 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):
| The study was terminated by the Sponsor. Only 3 participants were enrolled in this study. Based on the low enrollment number, no data is reported here in order to protect and maintain participant privacy/confidentiality. | Posted | Baseline to Week 24 |
|
The planned timeframe for adverse event (AE) collection was from the first dose of the study drug until the post-treatment follow-up period (baseline to Week 28). However, the study was terminated early by the sponsor. At the time of termination, 3 participants were enrolled and none completed the study. Enrolled subjects had a safety visit at 30 and 60 days following study drug discontinuation.
Three participants were enrolled and none completed the study. All participants were allocated to randomized treatment with AKST4290, and no participants received placebo.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | AKST4290 | Subjects will receive AKST4290, 400mg twice daily, for 24 weeks AKST4290: Oral AKST4290 | 0 | 3 | 0 | 3 | 2 | 3 |
| EG001 | Placebo | Subjects will receive matching Placebo, twice daily, for 24 weeks Placebo: Oral Placebo | 0 | 0 | 0 | 0 | 0 | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diabetes Mellitus | Metabolism and nutrition disorders | MedDRA 24.0 | Systematic Assessment | Worsening of Diabetes |
|
| Vitreous floaters | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Activated partial thromboplastin time prolonged | Investigations | MedDRA 24.0 | Systematic Assessment | Elevated APTT on labs |
|
This study was terminated by the Sponsor. Only 3 participants were enrolled in this study. Based on low enrollment number, no data is reported in order to protect and maintain participant privacy/confidentiality.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Head of Communications | Alkahest, Inc. | (650) 801-0474 | sm-Trials-alkahest@grifols.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 2, 2022 | Feb 16, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003930 | Diabetic Retinopathy |
| ID | Term |
|---|---|
| D012164 | Retinal Diseases |
| D005128 | Eye Diseases |
| D003925 | Diabetic Angiopathies |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D048909 | Diabetes Complications |
| D003920 | Diabetes Mellitus |
| D004700 | Endocrine System Diseases |
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| Participants |
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| Counts |
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| Participants |
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