Trial Outcomes & Findings for The TIME-2b Study: A Study of AKB-9778 (Razuprotafib), a Novel Tie 2 Activator, in Patients With Non-Proliferative Diabetic Retinopathy (NPDR) (NCT NCT03197870)

NCT ID: NCT03197870

Last Updated: 2023-06-27

Results Overview

Change from baseline to Week 48 in Diabetic Retinopathy Severity Scale Score in Study Eye by visit in the modified intent-to-treat population. ETDRS DR severity levels 10-85; ETDRS Steps 1-12

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

167 participants

Primary outcome timeframe

Baseline to Week 48

Results posted on

2023-06-27

Participant Flow

Participant milestones

Participant milestones
Measure	Razuprotafib 15mg Twice Daily Razuprotafib: Subcutaneous Razuprotafib 15mg	Razuprotafib 15mg Daily Razuprotafib: Subcutaneous Razuprotafib 15mg Placebo: Subcutaneous Placebo	Placebo Twice Daily Placebo: Subcutaneous Placebo
Overall Study STARTED	55	55	57
Overall Study COMPLETED	41	45	51
Overall Study NOT COMPLETED	14	10	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Razuprotafib 15mg Twice Daily Razuprotafib: Subcutaneous Razuprotafib 15mg	Razuprotafib 15mg Daily Razuprotafib: Subcutaneous Razuprotafib 15mg Placebo: Subcutaneous Placebo	Placebo Twice Daily Placebo: Subcutaneous Placebo
Overall Study Adverse Event	9	4	6
Overall Study Withdrawal by Subject	2	3	0
Overall Study Lost to Follow-up	2	2	0
Overall Study data not available	1	1	0

Baseline Characteristics

The "n" for this Baseline Characteristic does not match the overall population. The overall number of participants analyzed represents the total number of participants in each treatment group for the safety population. The summary included only those participants with available data.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Razuprotafib 15mg Twice Daily n=55 Participants Razuprotafib: Subcutaneous Razuprotafib 15mg	Razuprotafib 15mg Daily n=55 Participants Razuprotafib: Subcutaneous Razuprotafib 15mg Placebo: Subcutaneous Placebo	Placebo Twice Daily n=57 Participants Placebo: Subcutaneous Placebo	Total n=167 Participants Total of all reporting groups
Age, Continuous	56.7 years STANDARD_DEVIATION 11.17 • n=55 Participants	58.5 years STANDARD_DEVIATION 10.69 • n=55 Participants	55.9 years STANDARD_DEVIATION 9.88 • n=57 Participants	57.0 years STANDARD_DEVIATION 10.58 • n=167 Participants
Sex: Female, Male Female	23 Participants n=55 Participants	23 Participants n=55 Participants	25 Participants n=57 Participants	71 Participants n=167 Participants
Sex: Female, Male Male	32 Participants n=55 Participants	32 Participants n=55 Participants	32 Participants n=57 Participants	96 Participants n=167 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	25 Participants n=55 Participants	20 Participants n=55 Participants	25 Participants n=57 Participants	70 Participants n=167 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	30 Participants n=55 Participants	35 Participants n=55 Participants	32 Participants n=57 Participants	97 Participants n=167 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=55 Participants	0 Participants n=55 Participants	0 Participants n=57 Participants	0 Participants n=167 Participants
Race/Ethnicity, Customized American Indian/Native Alaskan	1 Participants n=55 Participants	0 Participants n=55 Participants	2 Participants n=57 Participants	3 Participants n=167 Participants
Race/Ethnicity, Customized Asian	2 Participants n=55 Participants	3 Participants n=55 Participants	1 Participants n=57 Participants	6 Participants n=167 Participants
Race/Ethnicity, Customized Black/African American	4 Participants n=55 Participants	7 Participants n=55 Participants	3 Participants n=57 Participants	14 Participants n=167 Participants
Race/Ethnicity, Customized Native Hawaiian/Pacific Islander	0 Participants n=55 Participants	0 Participants n=55 Participants	1 Participants n=57 Participants	1 Participants n=167 Participants
Race/Ethnicity, Customized White	47 Participants n=55 Participants	45 Participants n=55 Participants	49 Participants n=57 Participants	141 Participants n=167 Participants
Race/Ethnicity, Customized Other	1 Participants n=55 Participants	0 Participants n=55 Participants	1 Participants n=57 Participants	2 Participants n=167 Participants
Body Mass Index, kg/m²	31.91 kg/m² STANDARD_DEVIATION 4.776 • n=55 Participants	29.63 kg/m² STANDARD_DEVIATION 5.138 • n=55 Participants	30.58 kg/m² STANDARD_DEVIATION 4.752 • n=57 Participants	30.71 kg/m² STANDARD_DEVIATION 4.949 • n=167 Participants
Hemoglobin A1c, %	8.58 % of Glycated hemoglobin STANDARD_DEVIATION 1.380 • n=55 Participants	8.31 % of Glycated hemoglobin STANDARD_DEVIATION 1.885 • n=55 Participants	8.18 % of Glycated hemoglobin STANDARD_DEVIATION 1.457 • n=57 Participants	8.35 % of Glycated hemoglobin STANDARD_DEVIATION 1.587 • n=167 Participants
Type of Diabetes, n (%) Type 1	6 Participants n=55 Participants	6 Participants n=55 Participants	4 Participants n=57 Participants	16 Participants n=167 Participants
Type of Diabetes, n (%) Type 2	49 Participants n=55 Participants	49 Participants n=55 Participants	53 Participants n=57 Participants	151 Participants n=167 Participants
Duration of Diabetes, years	17.83 years STANDARD_DEVIATION 12.232 • n=55 Participants	17.78 years STANDARD_DEVIATION 11.001 • n=55 Participants	14.54 years STANDARD_DEVIATION 8.625 • n=57 Participants	16.69 years STANDARD_DEVIATION 10.749 • n=167 Participants
Taking Insulin, n (%) Yes	43 Participants n=55 Participants	37 Participants n=55 Participants	33 Participants n=57 Participants	113 Participants n=167 Participants
Taking Insulin, n (%) No	12 Participants n=55 Participants	18 Participants n=55 Participants	24 Participants n=57 Participants	54 Participants n=167 Participants
Taking Angiotensin-Converting Enzyme Inhibitor (ACEi)/Angiotensin Receptor Blocker (ARB) Yes	29 Participants n=55 Participants	39 Participants n=55 Participants	33 Participants n=57 Participants	101 Participants n=167 Participants
Taking Angiotensin-Converting Enzyme Inhibitor (ACEi)/Angiotensin Receptor Blocker (ARB) No	26 Participants n=55 Participants	16 Participants n=55 Participants	24 Participants n=57 Participants	66 Participants n=167 Participants
Study eye, n (%) Right Eye	27 Participants n=55 Participants	32 Participants n=55 Participants	26 Participants n=57 Participants	85 Participants n=167 Participants
Study eye, n (%) Left Eye	28 Participants n=55 Participants	23 Participants n=55 Participants	31 Participants n=57 Participants	82 Participants n=167 Participants
Duration of non-proliferative diabetic retinopathy in Study Eye, years	2.69 years STANDARD_DEVIATION 4.360 • n=51 Participants • The "n" for this Baseline Characteristic does not match the overall population. The overall number of participants analyzed represents the total number of participants in each treatment group for the safety population. The summary included only those participants with available data.	2.04 years STANDARD_DEVIATION 2.679 • n=51 Participants • The "n" for this Baseline Characteristic does not match the overall population. The overall number of participants analyzed represents the total number of participants in each treatment group for the safety population. The summary included only those participants with available data.	2.55 years STANDARD_DEVIATION 4.267 • n=54 Participants • The "n" for this Baseline Characteristic does not match the overall population. The overall number of participants analyzed represents the total number of participants in each treatment group for the safety population. The summary included only those participants with available data.	2.43 years STANDARD_DEVIATION 3.841 • n=156 Participants • The "n" for this Baseline Characteristic does not match the overall population. The overall number of participants analyzed represents the total number of participants in each treatment group for the safety population. The summary included only those participants with available data.
Duration of NPDR in qualified fellow eye, years	1.78 years STANDARD_DEVIATION 2.540 • n=13 Participants • Qualified fellow eyes only	2.00 years STANDARD_DEVIATION 3.282 • n=17 Participants • Qualified fellow eyes only	2.14 years STANDARD_DEVIATION 2.512 • n=20 Participants • Qualified fellow eyes only	2.00 years STANDARD_DEVIATION 2.750 • n=50 Participants • Qualified fellow eyes only
Prior Treatment for Proliferative Diabetic Retinopathy or Diabetic Macular Edema in Study Eye Yes	14 Participants n=55 Participants	7 Participants n=55 Participants	7 Participants n=57 Participants	28 Participants n=167 Participants
Prior Treatment for Proliferative Diabetic Retinopathy or Diabetic Macular Edema in Study Eye No	41 Participants n=55 Participants	48 Participants n=55 Participants	50 Participants n=57 Participants	139 Participants n=167 Participants
Prior Treatment for PDR or DME in Qualified Fellow Eye Yes	1 Participants n=13 Participants • If both eyes met all ocular eligibility criteria, then the eye with the worse ETDRS DRSS was designated the study eye, and the other eye designated as a qualified fellow eye; in this case, the Central Image Reading Center confirmed selection of the study eye. Not all subjects had a qualified fellow eye with prior treatment for PDR (Proliferative Diabetic Retinopathy).	2 Participants n=20 Participants • If both eyes met all ocular eligibility criteria, then the eye with the worse ETDRS DRSS was designated the study eye, and the other eye designated as a qualified fellow eye; in this case, the Central Image Reading Center confirmed selection of the study eye. Not all subjects had a qualified fellow eye with prior treatment for PDR (Proliferative Diabetic Retinopathy).	5 Participants n=22 Participants • If both eyes met all ocular eligibility criteria, then the eye with the worse ETDRS DRSS was designated the study eye, and the other eye designated as a qualified fellow eye; in this case, the Central Image Reading Center confirmed selection of the study eye. Not all subjects had a qualified fellow eye with prior treatment for PDR (Proliferative Diabetic Retinopathy).	8 Participants n=55 Participants • If both eyes met all ocular eligibility criteria, then the eye with the worse ETDRS DRSS was designated the study eye, and the other eye designated as a qualified fellow eye; in this case, the Central Image Reading Center confirmed selection of the study eye. Not all subjects had a qualified fellow eye with prior treatment for PDR (Proliferative Diabetic Retinopathy).
Prior Treatment for PDR or DME in Qualified Fellow Eye No	12 Participants n=13 Participants • If both eyes met all ocular eligibility criteria, then the eye with the worse ETDRS DRSS was designated the study eye, and the other eye designated as a qualified fellow eye; in this case, the Central Image Reading Center confirmed selection of the study eye. Not all subjects had a qualified fellow eye with prior treatment for PDR (Proliferative Diabetic Retinopathy).	18 Participants n=20 Participants • If both eyes met all ocular eligibility criteria, then the eye with the worse ETDRS DRSS was designated the study eye, and the other eye designated as a qualified fellow eye; in this case, the Central Image Reading Center confirmed selection of the study eye. Not all subjects had a qualified fellow eye with prior treatment for PDR (Proliferative Diabetic Retinopathy).	17 Participants n=22 Participants • If both eyes met all ocular eligibility criteria, then the eye with the worse ETDRS DRSS was designated the study eye, and the other eye designated as a qualified fellow eye; in this case, the Central Image Reading Center confirmed selection of the study eye. Not all subjects had a qualified fellow eye with prior treatment for PDR (Proliferative Diabetic Retinopathy).	47 Participants n=55 Participants • If both eyes met all ocular eligibility criteria, then the eye with the worse ETDRS DRSS was designated the study eye, and the other eye designated as a qualified fellow eye; in this case, the Central Image Reading Center confirmed selection of the study eye. Not all subjects had a qualified fellow eye with prior treatment for PDR (Proliferative Diabetic Retinopathy).
Diabetic Retinopathy Severity Scale Score in Study Eye	4.8 units on a scale STANDARD_DEVIATION 0.70 • n=55 Participants	4.9 units on a scale STANDARD_DEVIATION 0.70 • n=55 Participants	4.9 units on a scale STANDARD_DEVIATION 0.68 • n=57 Participants	4.9 units on a scale STANDARD_DEVIATION 0.69 • n=167 Participants
Best-Corrected Visual Acuity in Study Eye, Letters	82.4 letter score STANDARD_DEVIATION 5.41 • n=55 Participants	82.2 letter score STANDARD_DEVIATION 6.40 • n=55 Participants	83.5 letter score STANDARD_DEVIATION 6.33 • n=57 Participants	82.7 letter score STANDARD_DEVIATION 6.06 • n=167 Participants

PRIMARY outcome

Timeframe: Baseline to Week 48

Population: The modified intent-to-treat population consisted of all enrolled subjects who received at least 1 dose of study medication and was the population used for the efficacy population.

Change from baseline to Week 48 in Diabetic Retinopathy Severity Scale Score in Study Eye by visit in the modified intent-to-treat population. ETDRS DR severity levels 10-85; ETDRS Steps 1-12

Outcome measures

Outcome measures
Measure	Razuprotafib 15mg Twice Daily n=52 eyes Razuprotafib: Subcutaneous Razuprotafib 15mg	Razuprotafib 15mg Daily n=52 eyes Razuprotafib: Subcutaneous Razuprotafib 15mg Placebo: Subcutaneous Placebo	Placebo Twice Daily n=53 eyes Placebo: Subcutaneous Placebo
Percentage of Subjects With an Improvement in Study Eye Severity of Diabetic Retinopathy (DR) (ETDRS DR Severity Score or DRSS) of ≥ 2 Steps	0 eyes	5 eyes	2 eyes

SECONDARY outcome

Timeframe: Baseline to Week 48

Population: The modified intent-to-treat population consisted of all enrolled subjects who received at least 1 dose of study medication and was the population used for the efficacy population.

Worsening of Diabetic Retinopathy Severity Score (DRSS) severity of ≥ 2 steps in study eyes at Week 48 (compared to placebo group) Grading will follow Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) criteria. DRSS grades ranging from 10-85 will be converted to an ordinal score ranging from 1-11. ETDRS DRSS Level 10 = No retinopathy ETDRS DRSS Level 20 = Very mild NPDR ETDRS DRSS Level 35 = Mild NPDR ETDRS DRSS Level 43 = Moderate NPDR ETDRS DRSS Level 53 = Severe NPDR ETDRS DRSS Level 61 = Mild PDR ETDRS DRSS Level 65 = Moderate PDR ETDRS DRSS Level 71-75 = High-Risk PDR ETDRS DRSS Level 81-85 = Advanced PDR

Outcome measures

Outcome measures
Measure	Razuprotafib 15mg Twice Daily n=52 study eyes Razuprotafib: Subcutaneous Razuprotafib 15mg	Razuprotafib 15mg Daily n=52 study eyes Razuprotafib: Subcutaneous Razuprotafib 15mg Placebo: Subcutaneous Placebo	Placebo Twice Daily n=53 study eyes Placebo: Subcutaneous Placebo
Summary of Subjects With a Worsening in the Study Eye DRSS of ≥ 2 Steps at Week 48	5 study eyes	6 study eyes	4 study eyes

SECONDARY outcome

Timeframe: Week 48

Population: Modified Intent-to-Treat Population With at Least 1 Scheduled Post-Baseline Measure (LOCF)

Mean change from baseline in Diabetic Retinopathy Severity Score (DRSS) in the study eye at week 48. Note: Observed values at Week 48 instead of change from baseline values at Week 48 were analyzed Grading will follow Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) criteria. DRSS grades ranging from 10-85 will be converted to an ordinal score ranging from 1-11. ETDRS DRSS Level 10 = No retinopathy ETDRS DRSS Level 20 = Very mild NPDR ETDRS DRSS Level 35 = Mild NPDR ETDRS DRSS Level 43 = Moderate NPDR ETDRS DRSS Level 53 = Severe NPDR ETDRS DRSS Level 61 = Mild PDR ETDRS DRSS Level 65 = Moderate PDR ETDRS DRSS Level 71-75 = High-Risk PDR ETDRS DRSS Level 81-85 = Advanced PDR

Outcome measures

Outcome measures
Measure	Razuprotafib 15mg Twice Daily n=52 Participants Razuprotafib: Subcutaneous Razuprotafib 15mg	Razuprotafib 15mg Daily n=52 Participants Razuprotafib: Subcutaneous Razuprotafib 15mg Placebo: Subcutaneous Placebo	Placebo Twice Daily n=53 Participants Placebo: Subcutaneous Placebo
Mean Change From Baseline in DRSS in the Study Eye at Week 48	5.0 score on a scale Standard Deviation 1.15	4.9 score on a scale Standard Deviation 1.55	4.8 score on a scale Standard Deviation 1.35

SECONDARY outcome

Timeframe: Baseline to Week 48

Population: The modified intent-to-treat population consisted of all enrolled subjects who received at least 1 dose of study medication and was the population used for the efficacy population.

Summary of subjects with an improvement or worsening in the study eye Diabetic Retinopathy Severity Score (DRSS) of ≥ 3 steps at Week 48 (compared to placebo) Grading will follow Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) criteria. DRSS grades ranging from 10-85 will be converted to an ordinal score ranging from 1-11. ETDRS DRSS Level 10 = No retinopathy ETDRS DRSS Level 20 = Very mild NPDR ETDRS DRSS Level 35 = Mild NPDR ETDRS DRSS Level 43 = Moderate NPDR ETDRS DRSS Level 53 = Severe NPDR ETDRS DRSS Level 61 = Mild PDR ETDRS DRSS Level 65 = Moderate PDR ETDRS DRSS Level 71-75 = High-Risk PDR ETDRS DRSS Level 81-85 = Advanced PDR

Outcome measures

Outcome measures
Measure	Razuprotafib 15mg Twice Daily n=52 study eyes Razuprotafib: Subcutaneous Razuprotafib 15mg	Razuprotafib 15mg Daily n=52 study eyes Razuprotafib: Subcutaneous Razuprotafib 15mg Placebo: Subcutaneous Placebo	Placebo Twice Daily n=53 study eyes Placebo: Subcutaneous Placebo
Summary of Subjects With an Improvement or Worsening in the Study Eye DRSS of ≥ 3 Steps at Week 48. Improvement ≥3 steps	0 study eyes	0 study eyes	0 study eyes
Summary of Subjects With an Improvement or Worsening in the Study Eye DRSS of ≥ 3 Steps at Week 48. Worsening ≥3 steps	3 study eyes	4 study eyes	3 study eyes

SECONDARY outcome

Timeframe: Treatment Period - 12 months (48 weeks)

Population: Modified Intent-to-Treat Population with at least 1 scheduled Post-Baseline Measure (LOCF)

Subjects with Criterion Step Improvement in Diabetic Retinopathy Severity Score (DRSS) at Week 48/EOT (\>=2 Steps Improvement in the Study Eye for Patients with Non-qualified Fellow Eye and \>=3 Steps Improvement on the Person Scale for Patients with Qualified Fellow Eyes). Grading will follow Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) criteria. DRSS grades ranging from 10-85 will be converted to an ordinal score ranging from 1-11. ETDRS DRSS Level 10 = No retinopathy ETDRS DRSS Level 20 = Very mild NPDR ETDRS DRSS Level 35 = Mild NPDR ETDRS DRSS Level 43 = Moderate NPDR ETDRS DRSS Level 53 = Severe NPDR ETDRS DRSS Level 61 = Mild PDR ETDRS DRSS Level 65 = Moderate PDR ETDRS DRSS Level 71-75 = High-Risk PDR ETDRS DRSS Level 81-85 = Advanced PDR

Outcome measures

Outcome measures
Measure	Razuprotafib 15mg Twice Daily n=52 Participants Razuprotafib: Subcutaneous Razuprotafib 15mg	Razuprotafib 15mg Daily n=52 Participants Razuprotafib: Subcutaneous Razuprotafib 15mg Placebo: Subcutaneous Placebo	Placebo Twice Daily n=53 Participants Placebo: Subcutaneous Placebo
Subjects With Criterion Step Improvement in DRSS at Week 48/EOT (>=2 Steps Improvement in the Study Eye for Patients With Non-qualified Fellow Eye and >=3 Steps Improvement on the Person Scale for Patients With Qualified Fellow Eyes)	0 Participants	5 Participants	1 Participants

SECONDARY outcome

Timeframe: Treatment Period - 12 months (48 weeks)

Population: Modified Intent-to-Treat Population with at least 1 scheduled Post-Baseline Measure (LOCF)

Subjects With Criterion Step Improvement in Diabetic Retinopathy Severity Score (DRSS) at Week 48/EOT (\>=2 Steps Improvement in the Study Eye for Patients With Non-qualified Fellow Eye and \>=3 Steps Improvement on the Binocular Scale for Patients With Qualified Fellow Eyes). Grading will follow Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) criteria. DRSS grades ranging from 10-85 will be converted to an ordinal score ranging from 1-11. ETDRS DRSS Level 10 = No retinopathy ETDRS DRSS Level 20 = Very mild NPDR ETDRS DRSS Level 35 = Mild NPDR ETDRS DRSS Level 43 = Moderate NPDR ETDRS DRSS Level 53 = Severe NPDR ETDRS DRSS Level 61 = Mild PDR ETDRS DRSS Level 65 = Moderate PDR ETDRS DRSS Level 71-75 = High-Risk PDR ETDRS DRSS Level 81-85 = Advanced PDR

Outcome measures

Outcome measures
Measure	Razuprotafib 15mg Twice Daily n=52 Participants Razuprotafib: Subcutaneous Razuprotafib 15mg	Razuprotafib 15mg Daily n=52 Participants Razuprotafib: Subcutaneous Razuprotafib 15mg Placebo: Subcutaneous Placebo	Placebo Twice Daily n=53 Participants Placebo: Subcutaneous Placebo
Subjects With Criterion Step Improvement in DRSS at Week 48/EOT (>=2 Steps Improvement in the Study Eye for Patients With Non-qualified Fellow Eye and >=3 Steps Improvement on the Binocular Scale for Patients With Qualified Fellow Eyes)	0 Participants	5 Participants	1 Participants

SECONDARY outcome

Timeframe: Treatment Period - 12 months (48 weeks)

Population: mITT Population With ≥1 Scheduled Post-Baseline Measure (LOCF)

Summary of patients developing center-involved Diabetic Macular Edema (DME) or Proliferative Diabetic Retinopathy (PDR) or PDR-related outcomes during treatment period based on Clinical Data. Based on either clinical data or central image reading center evaluation.

Outcome measures

Outcome measures
Measure	Razuprotafib 15mg Twice Daily n=52 study eyes Razuprotafib: Subcutaneous Razuprotafib 15mg	Razuprotafib 15mg Daily n=52 study eyes Razuprotafib: Subcutaneous Razuprotafib 15mg Placebo: Subcutaneous Placebo	Placebo Twice Daily n=53 study eyes Placebo: Subcutaneous Placebo
Summary of Patients Developing Center-involved DME or PDR or PDR-related Outcomes During Treatment Period Based on Clinical Data.	12 study eyes	10 study eyes	10 study eyes

SECONDARY outcome

Timeframe: Treatment Period - 12 months (48 weeks)

Population: Modified Intent-to-Treat Population With at Least 1 Scheduled Post-Baseline Measure (LOCF)

Summary of Subjects Developing Center-involved Diabetic Macular Edema (DME) or Proliferative Diabetic Retinopathy (PDR) or Worsening of \>=2 Steps Diabetic Retinopathy Severity Scale (DRSS) at Week 48 Based on Central Image Reading Center Evaluation - Study Eyes Grading will follow Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) criteria. DRSS grades ranging from 10-85 will be converted to an ordinal score ranging from 1-11. ETDRS DRSS Level 10 = No retinopathy ETDRS DRSS Level 20 = Very mild NPDR ETDRS DRSS Level 35 = Mild NPDR ETDRS DRSS Level 43 = Moderate NPDR ETDRS DRSS Level 53 = Severe NPDR ETDRS DRSS Level 61 = Mild PDR ETDRS DRSS Level 65 = Moderate PDR ETDRS DRSS Level 71-75 = High-Risk PDR ETDRS DRSS Level 81-85 = Advanced PDR

Outcome measures

Outcome measures
Measure	Razuprotafib 15mg Twice Daily n=52 Participants Razuprotafib: Subcutaneous Razuprotafib 15mg	Razuprotafib 15mg Daily n=52 Participants Razuprotafib: Subcutaneous Razuprotafib 15mg Placebo: Subcutaneous Placebo	Placebo Twice Daily n=53 Participants Placebo: Subcutaneous Placebo
Summary of Subjects Developing Center-involved DME or PDR or Worsening of >=2 Steps DRSS at Week 48 Based on Central Image Reading Center Evaluation	10 Participants	8 Participants	7 Participants

Adverse Events

Razuprotafib 15mg Twice Daily

Serious events: 8 serious events

Other events: 55 other events

Deaths: 0 deaths

Razuprotafib 15mg Daily

Serious events: 6 serious events

Other events: 55 other events

Deaths: 0 deaths

Placebo Twice Daily

Serious events: 5 serious events

Other events: 57 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

David Bauer

EyePoint Pharmaceuticals, Inc

Phone: 8573410747

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Principal Investigators are not employed by the organization sponsoring the study
Publication restrictions are in place

Restriction type: OTHER

Measure	Razuprotafib 15mg Twice Daily n=55 participants at risk Razuprotafib: Subcutaneous Razuprotafib 15mg	Razuprotafib 15mg Daily n=55 participants at risk Razuprotafib: Subcutaneous Razuprotafib 15mg Placebo: Subcutaneous Placebo	Placebo Twice Daily n=57 participants at risk Placebo: Subcutaneous Placebo
Infections and infestations Osteomyelitis	3.6% 2/55 • Number of events 2 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/57 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]
Infections and infestations Burn infection	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	1.8% 1/57 • Number of events 1 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]
Infections and infestations Diabetic gangrene	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	1.8% 1/55 • Number of events 1 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/57 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]
Infections and infestations Influenza	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	1.8% 1/55 • Number of events 1 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/57 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]
Infections and infestations Perineal abscess	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	1.8% 1/55 • Number of events 1 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/57 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]
Infections and infestations Pneumonia	1.8% 1/55 • Number of events 1 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/57 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]
Cardiac disorders Myocardial infarction	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	3.5% 2/57 • Number of events 2 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]
Cardiac disorders Acute myocardial infarction	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	1.8% 1/57 • Number of events 1 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]
Cardiac disorders Atrioventricular block complete	1.8% 1/55 • Number of events 1 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/57 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]
Cardiac disorders Cardiac failure congestive	1.8% 1/55 • Number of events 1 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/57 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]
Cardiac disorders Coronary artery disease	1.8% 1/55 • Number of events 1 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/57 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]
Cardiac disorders Left ventricular failure	1.8% 1/55 • Number of events 1 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/57 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]
Gastrointestinal disorders Mallory-Weiss syndrome	1.8% 1/55 • Number of events 1 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	1.8% 1/55 • Number of events 1 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/57 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]
Gastrointestinal disorders Oesophageal stenosis	1.8% 1/55 • Number of events 1 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/57 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]
Gastrointestinal disorders Vomiting	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	1.8% 1/55 • Number of events 1 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/57 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]
Vascular disorders Hypotension	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	1.8% 1/55 • Number of events 1 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/57 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]
Vascular disorders Orthostatic hypotension	1.8% 1/55 • Number of events 1 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/57 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]
Blood and lymphatic system disorders Anaemia	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	1.8% 1/55 • Number of events 1 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/57 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]
General disorders Chest pain	1.8% 1/55 • Number of events 1 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/57 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]
Musculoskeletal and connective tissue disorders Back pain	1.8% 1/55 • Number of events 1 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/57 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	1.8% 1/55 • Number of events 1 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/57 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]
Nervous system disorders Cerebrovascular accident	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	1.8% 1/55 • Number of events 1 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/57 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]
Renal and urinary disorders Nephrolithiasis	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	1.8% 1/57 • Number of events 1 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.8% 1/55 • Number of events 1 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/55 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]	0.00% 0/57 • Adverse events were collected from Screening through the last protocol specified visit [approximately 56 weeks (Screening period up to 4 weeks, Baseline and Treatment period for 48 weeks, and Follow-up period for 4 weeks)]