Trial Outcomes & Findings for A Study to Assess the Efficacy and Safety of AKST4290 With Aflibercept in Patients With Newly Diagnosed nAMD (NCT NCT04331730)
NCT ID: NCT04331730
Last Updated: 2022-10-26
Results Overview
Mean change from baseline in Best Corrected Visual Acuity (BCVA) per the Early Treatment Diabetic Retinopathy Study (ETDRS) testing method. BCVA will be assessed using ETDRS charts at 4 meters initial testing distance and assessed in both eyes. Score range is 0 to 93. A higher score indicates better vision.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
107 participants
Primary outcome timeframe
Baseline to Week 36
Results posted on
2022-10-26
Participant Flow
Participant milestones
| Measure |
AKST4290 (800 mg) + Aflibercept
Subjects will receive 400 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
AKST4290: Oral AKST4290
Aflibercept: Aflibercept intravitreal injection
|
AKST4290 (1600 mg) + Aflibercept
Subjects will receive 800 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
AKST4290: Oral AKST4290
Aflibercept: Aflibercept intravitreal injection
|
Placebo + Aflibercept
Subjects will receive placebo for 36 weeks, in combination with intravitreal aflibercept injection treatment
Placebo: Oral placebo
Aflibercept: Aflibercept intravitreal injection
|
|---|---|---|---|
|
Overall Study
STARTED
|
36
|
35
|
36
|
|
Overall Study
COMPLETED
|
36
|
29
|
34
|
|
Overall Study
NOT COMPLETED
|
0
|
6
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Assess the Efficacy and Safety of AKST4290 With Aflibercept in Patients With Newly Diagnosed nAMD
Baseline characteristics by cohort
| Measure |
AKST4290 (800 mg) + Aflibercept
n=36 Participants
Subjects will receive 400 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
AKST4290: Oral AKST4290
Aflibercept: Aflibercept intravitreal injection
|
AKST4290 (1600 mg) + Aflibercept
n=35 Participants
Subjects will receive 800 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
AKST4290: Oral AKST4290
Aflibercept: Aflibercept intravitreal injection
|
Placebo + Aflibercept
n=36 Participants
Subjects will receive placebo for 36 weeks, in combination with intravitreal aflibercept injection treatment
Placebo: Oral placebo
Aflibercept: Aflibercept intravitreal injection
|
Total
n=107 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Race (NIH/OMB)
White
|
36 Participants
n=93 Participants
|
35 Participants
n=4 Participants
|
35 Participants
n=27 Participants
|
106 Participants
n=483 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
|
Age, Continuous
|
76.4 years
STANDARD_DEVIATION 8.84 • n=93 Participants
|
74.7 years
STANDARD_DEVIATION 7.42 • n=4 Participants
|
73.8 years
STANDARD_DEVIATION 9.34 • n=27 Participants
|
75.0 years
STANDARD_DEVIATION 8.57 • n=483 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=93 Participants
|
25 Participants
n=4 Participants
|
21 Participants
n=27 Participants
|
68 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=93 Participants
|
10 Participants
n=4 Participants
|
15 Participants
n=27 Participants
|
39 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
2 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
35 Participants
n=93 Participants
|
35 Participants
n=4 Participants
|
35 Participants
n=27 Participants
|
105 Participants
n=483 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Region of Enrollment
Hungary
|
5 participants
n=93 Participants
|
4 participants
n=4 Participants
|
4 participants
n=27 Participants
|
13 participants
n=483 Participants
|
|
Region of Enrollment
United States
|
2 participants
n=93 Participants
|
3 participants
n=4 Participants
|
2 participants
n=27 Participants
|
7 participants
n=483 Participants
|
|
Region of Enrollment
Poland
|
29 participants
n=93 Participants
|
28 participants
n=4 Participants
|
30 participants
n=27 Participants
|
87 participants
n=483 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 36Mean change from baseline in Best Corrected Visual Acuity (BCVA) per the Early Treatment Diabetic Retinopathy Study (ETDRS) testing method. BCVA will be assessed using ETDRS charts at 4 meters initial testing distance and assessed in both eyes. Score range is 0 to 93. A higher score indicates better vision.
Outcome measures
| Measure |
AKST4290 (800 mg) + Aflibercept
n=36 Participants
Subjects will receive 400 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
AKST4290: Oral AKST4290
Aflibercept: Aflibercept intravitreal injection
|
AKST4290 (1600 mg) + Aflibercept
n=35 Participants
Subjects will receive 800 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
AKST4290: Oral AKST4290
Aflibercept: Aflibercept intravitreal injection
|
Placebo + Aflibercept
n=36 Participants
Subjects will receive placebo for 36 weeks, in combination with intravitreal aflibercept injection treatment
Placebo: Oral placebo
Aflibercept: Aflibercept intravitreal injection
|
|---|---|---|---|
|
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Per the Early Treatment Diabetic Retinopathy Study (ETDRS) Testing Method
|
10.4 score on a scale
Standard Deviation 10.26
|
6.7 score on a scale
Standard Deviation 7.89
|
13.7 score on a scale
Standard Deviation 7.60
|
SECONDARY outcome
Timeframe: Baseline to Week 36Time to first use of intravitreal aflibercept injection, as needed (AKST4290 Arms only). UNITS: weeks.
Outcome measures
| Measure |
AKST4290 (800 mg) + Aflibercept
n=36 Participants
Subjects will receive 400 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
AKST4290: Oral AKST4290
Aflibercept: Aflibercept intravitreal injection
|
AKST4290 (1600 mg) + Aflibercept
n=35 Participants
Subjects will receive 800 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
AKST4290: Oral AKST4290
Aflibercept: Aflibercept intravitreal injection
|
Placebo + Aflibercept
Subjects will receive placebo for 36 weeks, in combination with intravitreal aflibercept injection treatment
Placebo: Oral placebo
Aflibercept: Aflibercept intravitreal injection
|
|---|---|---|---|
|
Time to PRN Injection (Arms 1 and 2 Only)
|
20.6 weeks
Interval 19.0 to 24.4
|
20.1 weeks
Interval 17.0 to 21.7
|
—
|
SECONDARY outcome
Timeframe: Week 12 to Week 36Population: The number of injections received per week is defined as the number of IAIs received on or after Week 12 (PRN or scheduled injections) divided by (the analysis Week visit date \[or EOS date if subject terminates study early\] minus date of Week 12 visit plus one, divided by seven). Data reported reflects subjects with available data for those having received injections from week 12.
Median number of injections received beginning at Week 12 as a rate. UNITS: number of injections per week from Week 12
Outcome measures
| Measure |
AKST4290 (800 mg) + Aflibercept
n=36 Participants
Subjects will receive 400 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
AKST4290: Oral AKST4290
Aflibercept: Aflibercept intravitreal injection
|
AKST4290 (1600 mg) + Aflibercept
n=34 Participants
Subjects will receive 800 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
AKST4290: Oral AKST4290
Aflibercept: Aflibercept intravitreal injection
|
Placebo + Aflibercept
n=35 Participants
Subjects will receive placebo for 36 weeks, in combination with intravitreal aflibercept injection treatment
Placebo: Oral placebo
Aflibercept: Aflibercept intravitreal injection
|
|---|---|---|---|
|
Median Number of Aflibercept Injections Received Beginning at Week 12
|
0.082 number of injections per week
Interval 0.041 to 0.124
|
0.083 number of injections per week
Interval 0.042 to 0.124
|
0.125 number of injections per week
Interval 0.123 to 0.159
|
SECONDARY outcome
Timeframe: Baseline to Week 36Percentage of subjects with Best Corrected Visual Acuity (BCVA) change of ≥ 15 letters at Week 36.
Outcome measures
| Measure |
AKST4290 (800 mg) + Aflibercept
n=36 Participants
Subjects will receive 400 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
AKST4290: Oral AKST4290
Aflibercept: Aflibercept intravitreal injection
|
AKST4290 (1600 mg) + Aflibercept
n=35 Participants
Subjects will receive 800 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
AKST4290: Oral AKST4290
Aflibercept: Aflibercept intravitreal injection
|
Placebo + Aflibercept
n=36 Participants
Subjects will receive placebo for 36 weeks, in combination with intravitreal aflibercept injection treatment
Placebo: Oral placebo
Aflibercept: Aflibercept intravitreal injection
|
|---|---|---|---|
|
Percentage of Subjects With Best Corrected Visual Acuity (BCVA) Change of ≥ 15 Letters
|
30.6 percentage of participants
Interval 16.3 to 48.1
|
14.3 percentage of participants
Interval 4.8 to 30.3
|
41.7 percentage of participants
Interval 25.5 to 59.2
|
SECONDARY outcome
Timeframe: Baseline to Week 12Mean change in Central Subfield Thickness (CST) compared with control through Week 12. UNITS: micrometre
Outcome measures
| Measure |
AKST4290 (800 mg) + Aflibercept
n=36 Participants
Subjects will receive 400 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
AKST4290: Oral AKST4290
Aflibercept: Aflibercept intravitreal injection
|
AKST4290 (1600 mg) + Aflibercept
n=35 Participants
Subjects will receive 800 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
AKST4290: Oral AKST4290
Aflibercept: Aflibercept intravitreal injection
|
Placebo + Aflibercept
n=36 Participants
Subjects will receive placebo for 36 weeks, in combination with intravitreal aflibercept injection treatment
Placebo: Oral placebo
Aflibercept: Aflibercept intravitreal injection
|
|---|---|---|---|
|
Mean Change in Central Subfield Thickness (CST) Compared With Control Through Week 12
|
-135.3 micrometre
Standard Deviation 122.66
|
-162.7 micrometre
Standard Deviation 118.91
|
-159.5 micrometre
Standard Deviation 128.00
|
SECONDARY outcome
Timeframe: Screening to Week 40Number of Participants with Adverse Events categorized by intensity
Outcome measures
| Measure |
AKST4290 (800 mg) + Aflibercept
n=36 Participants
Subjects will receive 400 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
AKST4290: Oral AKST4290
Aflibercept: Aflibercept intravitreal injection
|
AKST4290 (1600 mg) + Aflibercept
n=35 Participants
Subjects will receive 800 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
AKST4290: Oral AKST4290
Aflibercept: Aflibercept intravitreal injection
|
Placebo + Aflibercept
n=36 Participants
Subjects will receive placebo for 36 weeks, in combination with intravitreal aflibercept injection treatment
Placebo: Oral placebo
Aflibercept: Aflibercept intravitreal injection
|
|---|---|---|---|
|
Number of Participants With Adverse Events Assessed by Intensity
Mild TEAE
|
15 Participants
|
10 Participants
|
11 Participants
|
|
Number of Participants With Adverse Events Assessed by Intensity
Moderate TEAE
|
8 Participants
|
7 Participants
|
8 Participants
|
|
Number of Participants With Adverse Events Assessed by Intensity
Severe TEAE
|
3 Participants
|
9 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events Assessed by Intensity
No TEAE
|
10 Participants
|
9 Participants
|
16 Participants
|
SECONDARY outcome
Timeframe: Week 12 to Week 36Population: Reported data follows the pre-specified analyses and tables generated per the Statistical Analysis Plan for additional analyses of the primary endpoint. Change from Week 12 in BCVA ETDRS letters read is reported for the AKST4290 combined group and Placebo and will include a similar REML-based MMRM analysis as described for the primary endpoint; a covariate of letters read at Week 12 will be included in lieu of baseline letters read.
Mean change in Best Corrected Visual Acuity (BCVA) letter score per the Early Treatment Diabetic Retinopathy Study (ETDRS) testing method from Week 12 as compared to control at Week 36. BCVA will be assessed using ETDRS charts at 4 meters initial testing distance and assessed in both eyes. Score range is 0 to 93. A higher score indicates better vision.
Outcome measures
| Measure |
AKST4290 (800 mg) + Aflibercept
n=71 Participants
Subjects will receive 400 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
AKST4290: Oral AKST4290
Aflibercept: Aflibercept intravitreal injection
|
AKST4290 (1600 mg) + Aflibercept
n=36 Participants
Subjects will receive 800 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
AKST4290: Oral AKST4290
Aflibercept: Aflibercept intravitreal injection
|
Placebo + Aflibercept
Subjects will receive placebo for 36 weeks, in combination with intravitreal aflibercept injection treatment
Placebo: Oral placebo
Aflibercept: Aflibercept intravitreal injection
|
|---|---|---|---|
|
Mean Change in Best Corrected Visual Acuity (BCVA) Per the Early Treatment Diabetic Retinopathy Study (ETDRS) Testing Method as Compared With Control
|
1.1 score on a scale
Standard Deviation 5.98
|
2.3 score on a scale
Standard Deviation 5.35
|
—
|
SECONDARY outcome
Timeframe: Week 12 to the first visit meeting PRN injection criteria through week 36Population: Data reflects subjects having received injections from week 12. Subjects who do not experience the event of interest (i.e., receive a PRN injection, meet the criteria for PRN IAI) while on the study were censored at their last visit completed through Week 36, as applicable.
Time to the first visit where PRN injection criteria are met starting at Week 12 will be calculated in weeks as the first date where PRN injection criteria are first met minus the date of first dose of study drug plus one, divided by seven. Subjects who do not experience the event of interest (meet the criteria for PRN IAI) while on the study will be censored at their last visit completed through Week 36. Units: weeks
Outcome measures
| Measure |
AKST4290 (800 mg) + Aflibercept
n=29 Participants
Subjects will receive 400 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
AKST4290: Oral AKST4290
Aflibercept: Aflibercept intravitreal injection
|
AKST4290 (1600 mg) + Aflibercept
n=31 Participants
Subjects will receive 800 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
AKST4290: Oral AKST4290
Aflibercept: Aflibercept intravitreal injection
|
Placebo + Aflibercept
n=24 Participants
Subjects will receive placebo for 36 weeks, in combination with intravitreal aflibercept injection treatment
Placebo: Oral placebo
Aflibercept: Aflibercept intravitreal injection
|
|---|---|---|---|
|
Time to the First Visit Where PRN Injection Criteria Are Met
|
20.6 weeks
Interval 12.9 to 39.0
|
20.1 weeks
Interval 12.1 to 37.1
|
20.4 weeks
Interval 11.7 to 37.4
|
Adverse Events
AKST4290 (800 mg) + Aflibercept
Serious events: 3 serious events
Other events: 26 other events
Deaths: 0 deaths
AKST4290 (1600 mg) + Aflibercept
Serious events: 3 serious events
Other events: 26 other events
Deaths: 1 deaths
Placebo + Aflibercept
Serious events: 0 serious events
Other events: 20 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
AKST4290 (800 mg) + Aflibercept
n=36 participants at risk
Subjects will receive 400 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
AKST4290: Oral AKST4290
Aflibercept: Aflibercept intravitreal injection
|
AKST4290 (1600 mg) + Aflibercept
n=35 participants at risk
Subjects will receive 800 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
AKST4290: Oral AKST4290
Aflibercept: Aflibercept intravitreal injection
|
Placebo + Aflibercept
n=36 participants at risk
Subjects will receive placebo for 36 weeks, in combination with intravitreal aflibercept injection treatment
Placebo: Oral placebo
Aflibercept: Aflibercept intravitreal injection
|
|---|---|---|---|
|
Infections and infestations
COVID-19
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
5.7%
2/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Infections and infestations
Endophthalmitis
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
2.9%
1/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Infections and infestations
Pneumonia viral
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
2.9%
1/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Cardiac disorders
Left ventricular failure
|
2.8%
1/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Cardiac disorders
Supraventricular tachycardia
|
2.8%
1/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
2.8%
1/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
2.9%
1/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
Other adverse events
| Measure |
AKST4290 (800 mg) + Aflibercept
n=36 participants at risk
Subjects will receive 400 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
AKST4290: Oral AKST4290
Aflibercept: Aflibercept intravitreal injection
|
AKST4290 (1600 mg) + Aflibercept
n=35 participants at risk
Subjects will receive 800 mg AKST4290 twice daily for 36 weeks, in combination with intravitreal aflibercept injection treatment
AKST4290: Oral AKST4290
Aflibercept: Aflibercept intravitreal injection
|
Placebo + Aflibercept
n=36 participants at risk
Subjects will receive placebo for 36 weeks, in combination with intravitreal aflibercept injection treatment
Placebo: Oral placebo
Aflibercept: Aflibercept intravitreal injection
|
|---|---|---|---|
|
Investigations
Electrocardiogram QT prolonged
|
13.9%
5/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
8.6%
3/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
8.3%
3/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.3%
3/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
5.7%
2/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Eye disorders
Eye pain
|
8.3%
3/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
5.7%
2/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
13.9%
5/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Gastrointestinal disorders
Abdominal pain
|
2.8%
1/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
8.6%
3/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
2.8%
1/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Infections and infestations
COVID-19
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
11.4%
4/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
5.6%
2/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Nervous system disorders
Dizziness
|
8.3%
3/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
2.9%
1/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
11.4%
4/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Investigations
Alanine aminotransferase increased
|
2.8%
1/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
5.7%
2/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Investigations
Aspartate aminotransferase increased
|
2.8%
1/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
5.7%
2/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Nervous system disorders
Headache
|
2.8%
1/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
5.7%
2/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
5.6%
2/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
8.6%
3/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Investigations
Liver function test abnormal
|
2.8%
1/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
5.7%
2/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
2.8%
1/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
5.7%
2/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Investigations
Product residue present
|
8.3%
3/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
2.8%
1/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Infections and infestations
Urinary tract infection
|
5.6%
2/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
2.9%
1/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
5.6%
2/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.6%
2/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Investigations
Blood pressure increased
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
5.7%
2/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
2.8%
1/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Eye disorders
Conjunctival haemorrhage
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
5.7%
2/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Gastrointestinal disorders
Diarrhoea
|
5.6%
2/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
8.3%
3/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Injury, poisoning and procedural complications
Fall
|
5.6%
2/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Investigations
Glomerular filtration rate decreased
|
5.6%
2/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
2.8%
1/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
5.7%
2/35 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
0.00%
0/36 • From Screening through End of Study, approximately 42 weeks
AEs were captured beginning at time of informed consent through EOS. AE status was followed by the investigator until resolved or considered stable, unless the subject was lost to follow up
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60