Nesvategrast (OTT166) in Diabetic Retinopathy (DR)
- Registration Number
- NCT05409235
- Lead Sponsor
- OcuTerra Therapeutics, Inc.
- Brief Summary
This study will evaluate the safety and efficacy of OTT166 Ophthalmic solution in participants with Diabetic Retinopathy.
- Detailed Description
This randomized, double-masked, vehicle controlled, phase 2 study will evaluate the safety and efficacy of OTT166 ophthalmic solution in participants with diabetic retinopathy and select an optimum dosing regimen for Phase 3 pivotal trials. Approximately 210 participants diagnosed with moderately severe to severe non-proliferative diabetic retinopathy (NPDR) or mild proliferative diabetic retinopathy (PDR) and who are treatment naïve (ie, no prior anti-vascular endothelial growth factor \[anti-VEGF\] or laser \[focal, grid, pan-retinal photocoagulation (PRP)\] administered) will be randomized 2:2:1:1 into the following groups: OTT166 5% twice daily (BID), OTT166 5% four times daily (QID), vehicle control BID, vehicle control QID. Randomization will be stratified by baseline Diabetic Retinopathy Severity Scale (DRSS) score (47 or 53 or 61B). Participants with PDR (DRSS score 61B) will be capped at 20% of all randomized participants. Each group will self-administer one 50-μl eye drop of study solution (frequency as assigned) for 24 weeks.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 225
- Men or women ≥ 18 years of age with type 1 or 2 diabetes mellitus who have moderately severe to severe NPDR [DRSS levels 47 or 53], or mild PDR [DRSS level 61] NVE < 0.5 DA in 1 + quadrants], in whom PRP and/or anti-VEGF IVT can be safely deferred for at least 6 months per the Investigator
- BCVA ETDRS letter score in the study eye of ≥ 69 letters (approximate Snellen equivalent of 20/40 or better)
- Normal foveal contour
- Treatment naïve (ie, no previous anti-VEGF or steroid treatment or PRP or laser)
- Willing and able to return for all study visits and comply with study-related procedures
- Able to adhere to the study dosing requirements
- Understands and signs the written Informed Consent Form
-
CST of > 325 μm
a. Fluid in the central subfield is allowed so long as CST is ≤325 μm and there is a normal foveal contour as determined by the Central Reading Center
-
Any prior focal or grid laser photocoagulation or any prior PRP in the study eye as it pertains to treatment of DME or DR (peripheral retinal hole treated with laser is allowed)
-
Eyes with DRSS score 61 with fibrous proliferations at disc or fibrous proliferations elsewhere a. DRSS score 61B with NVE only is allowed. Any sign of fibrosis proliferation is exclusionary
-
Any prior systemic anti-VEGF treatment or IVT anti-VEGF treatment in the study eye
-
Any prior intraocular steroid injection in the study eye, inclusive of Iluvien® and Retisert® a. History of Ozurdex® and triamcinolone use prior to 12 months before study enrollment is allowed
-
Current ASNV, vitreous hemorrhage, or tractional retinal detachment visible at the screening assessments in the study eye
-
Uncontrolled glaucoma or ocular hypertension in the study eye defined as an IOP > 25 mmHg regardless of concomitant treatment with IOP-lowering medications
-
Hypertension defined as systolic > 180 mmHg or > 160 mmHg on 2 consecutive measurements (during the same visit) or diastolic > 100 mmHg
-
Screening HbA1c blood test > 12.0%
-
Renal failure (stage 4 or end-stage), dialysis, or history of renal transplant
-
History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect interpretation of the results of the study or render the participant at high risk for treatment complications
-
Initiation of intensive insulin treatment (a pump or multiple daily injections) within 4 months prior to randomization or plans to do so in the next 4 months
-
Epiretinal membrane, posterior hyaloidal traction, and/or vitreomacular traction in the study eye as determined to be significant by the Investigator
-
Previous pars plana vitrectomy in the study eye
-
Any intraocular surgery in the study eye within 90 days (3 months) prior to study enrollment
-
YAG laser treatment in the study eye within 90 days prior to study enrollment
-
Concomitant use of any topical ophthalmic medications in the study eye, including dry eye or glaucoma medications, unless on a stable dose for at least 90 days prior to study enrollment and expected to stay on stable dose throughout study participation. Topical eyedrops are allowed but not within ±10 minutes of study drop application
-
Contact lens use from time of screening throughout the study
-
Central corneal changes from dry eye that are visually significant and/or Sjogren's syndrome
-
Visually significant Fuchs endothelial dystrophy or other diagnosed conditions of corneal compromise including Anterior Basement Membrane Dystrophy, or any corneal dystrophy affecting central vision (peripheral processes are not exclusionary)
-
Chronic or recurrent uveitis in the study eye
-
Ongoing ocular infection or inflammation in either eye
-
A history of cataract surgery complicated by vitreous loss in the study eye
-
Congenital eye malformations in the study eye
-
A history of penetrating ocular trauma in the study eye
-
Cognitive impairment that, in the opinion of the investigator, could compromise compliance with the requirements of the study
-
Females of childbearing potential (ie, who are not postmenopausal for at least 1 year or surgically sterile for at least 6 weeks prior to Visit 1 - Screening/Randomization) who are lactating, or who are pregnant as determined by a positive serum pregnancy test at Visit 1 -Screening/Randomization. Women of childbearing potential must agree to use acceptable methods of birth control throughout the study a. Women who are breastfeeding or who have a positive serum hCG/urine pregnancy test at the screening or BL Visit
-
Females and males of childbearing potential unwilling or unable to utilize the following acceptable methods of birth control: tubal ligation, transdermal patch, intrauterine devices/systems, oral/implantable/injectable or contraceptives, diaphragm or cervical cap with spermicide, or vasectomized partner for females; condoms with spermicidal agent and vasectomy for males; or sexual abstinence for males and females
-
Participation in any other investigational device or drug clinical research study within 12 weeks of Visit 1 - Screening/Randomization and during the duration of enrollment
-
Contraindication to the study medications or fluorescein dye
-
Other ocular pathologies that, in the investigator's opinion, would interfere with the participant's vision in the study eye
-
Ocular media of insufficient quality to obtain fundus photographs, fluorescein angiography, and OCT images in the study eye
-
Concomitant use of Semaglutide (Wegovy®, Ozempic®, Rybelsus®), Thiazolidinediones (Actos®, Avandia®), Liraglutides (Victoza®, Saxenda®), Dulaglutide (Trulicity®), or Tirzepatide (Mounjaro®) within 12 months prior to Visit 1 (allowed if a stable dose has been established for at least 1 year of use) a. Plans to start concomitant use of Semaglutide or Thiazolidinediones during the study duration is exclusionary
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description OTT166 Cohort 1 OTT166 Participants will receive OTT166 5% twice a day (BID) for 24 weeks Vehicle control Cohort 1 Vehicle control Participants will receive vehicle control BID for 24 weeks Vehicle control Cohort 2 Vehicle control Participants will receive vehicle control QID for 24 weeks OTT166 Cohort 2 OTT166 Participants will receive OTT166 5% four times a day (QID) for 24 weeks
- Primary Outcome Measures
Name Time Method Proportion of Participants Who Improved by ≥ 2 Steps From Baseline in Diabetic Retinopathy Severity Scale (DRSS) Scores At week 24 To characterize the efficacy of topical OTT166 in participants with DR, the Diabetic Retinopathy Severity Scale (DRSS) was used. The DRSS ranges from 10 to 85 in 12 discrete steps with higher score representing worse DR. The DRSS values were determined by the central reading center. The data reported are the estimated percentage of participants that improved by at least 2 steps from baseline. The reported data include the use of imputation according to the primary estimand as described in the protocol.
- Secondary Outcome Measures
Name Time Method Development of PDR Worse Than Mild (Wtm) (DRSS 65 and Above) At week 24 To determine if topical OTT166 prevented or delayed the occurrence of worse than mild PDR (wtmPDR). The determination was made using Kaplan-Meier methodology. The estimated percentage that progressed to wtmPDR by Week 24 is reported. The reported data include the use of imputation according to the primary estimand as described in the protocol.
Proportion of Participants Who Developed CI-DME At week 24 To determine if topical OTT166 prevented or delayed the occurrence of CI-DME. CI-DME is defined as the presence of fluid in the central subfield in participants who have no fluid at baseline or CST\> 325 μm. The reported data include the use of imputation according to the primary estimand as described in the protocol.
The Development of CI-DME At week 24 To determine if topical OTT166 prevented or delayed the occurrence of CI-DME. CI-DME is defined as the presence of fluid in the central subfield in participants who have no fluid at baseline or CST\> 325 μm. The reported data include the use of imputation according to the primary estimand as described in the protocol. The percentages of participants that developed CI-DME at Week 24 are reported.
Proportion of Participants With Lines Gained/Lost of BCVA From Baseline (Day 1) up to Week 24 To determine the effect of OTT166 on BCVA in participants with moderately severe to severe NPDR and mild PDR. Proportion of participants who gained/lost lines of BCVA (± 5, 10, and 15 ETDRS letters) were assessed. The reported data include the use of imputation according to the primary estimand as described in the protocol. 5 ETDRS letters = 1 line.
Change From Baseline in Central Subfield Thickness (CST) From Baseline (Day 1) up to Week 24 To determine the effect of OTT166 on CST in participants with moderately severe to severe NPDR and mild PDR. CST was measured by optical coherence tomography (OCT).
Area Under The Curve (AUC) for Change From Baseline in CST From Baseline (Day 1) up to Week 24 To determine the effect of OTT166 on CST in participants with moderately severe to severe NPDR and mild PDR. CST was measured by OCT.
Proportion of Participants Who Met the Objective Rescue Criteria From Baseline (Day 1) up to Week 24 To determine the effect of OTT166 on the need for rescue therapy in participants with moderately severe to severe NPDR and mild PDR.
Proportion That Met Objective Rescue Therapy Criteria by Week 24 From Baseline (Day 1) up to Week 24 To determine the effect of OTT166 on the need for rescue therapy in participants with moderately severe to severe NPDR and mild PDR. The reported data include the use of imputation according to the primary estimand as described in the protocol.
Change From Baseline in Best Corrected Visual Acuity (BCVA) From Baseline (Day 1) up to Week 24 To determine the effect of OTT166 on BCVA in participants with moderately severe to severe NPDR and mild PDR. BCVA was assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) letters score. A higher score represents better visual function.
Proportion of Participants Who Developed ASNV At week 24 To determine if topical OTT166 prevented or delayed the occurrence of anterior segment neovascularization (ASNV). Measure is the percentage of patients that developed ASNV at 24 weeks. The reported data include the use of imputation according to the primary estimand as described in the protocol.
Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline At week 24 To determine the effect of OTT166 on DRSS in participants with moderately severe to severe NPDR and mild PDR treated with topical OTT166. Change in DRSS steps is defined as DR worsening or improving by 1, 2, or ≥ 3 steps along with no change. The reported data include the use of imputation according to the primary estimand as described in the protocol.
Proportion of Participants With Mild PDR at Baseline Who Regressed to NPDR At week 24 To determine the effect of OTT166 on DRSS in participants with mild PDR (DRSS 61B) treated with topical OTT166. Regression of disease was defined as decrease in DRSS to 53 or lower. The reported data include the use of imputation according to the primary estimand as described in the protocol.
Proportion of Participants That Developed Worse Than Mild PDR (DRSS 65 and Above) At week 24 To determine if topical OTT166 prevented or delayed the occurrence of worse than mild PDR, DRSS of 65 and above. The higher the DRSS, the greater the risk of vision loss and thus the standard of care is to treat affected patients aggressively. The reported data include the use of imputation according to the primary estimand as described in the protocol.
Proportion of Participants That Developed Visually Threatening Complications (VTC) Complications (VTC) At Week 24 To determine if topical OTT166 prevented or delayed the occurrence of a VTC. VTC is defined as the composite outcome of PDR and/or ASNV and/or CI-DME.
Time to Development of PDR Worse Than Mild (DRSS 65 and Above) or CI-DME From Baseline (Day 1) up to Week 24 To determine if topical OTT166 prevented or delayed the occurrence of PDR worse than mild (DRSS 65 and above) or CI-DME. CI-DME is defined as the presence of fluid in the central subfield in participants who have no fluid at baseline or CST\> 325 μm. Participants who experienced one or more events (worse than mild PDR and/or CI-DME), the earliest event date was selected. Participants who did not experience either event were censored at the earliest of the last available assessment. Median time to event is reported if calculable.
Area Under the Curve for BCVA (ETDRS Letters) From Baseline to Week 24 From Baseline (Day 1) up to Week 24 To determine the effect of OTT166 on BCVA in participants with moderately severe to severe NPDR and mild PDR. BCVA was assessed by ETDRS letters score. A higher score represents better functioning. AUC from baseline to 24 weeks is calculated by the linear trapezoidal method.
Percentages of Participants at Week 24 That Had Had Rescue Therapy Administered 24 Weeks To determine the impact of treatment with OTT166 on the time to receiving rescue therapy. Analysis was performed using the Kaplan-Meier methodology. The reported data include the use of imputation according to the primary estimand as described in the protocol. The data reported are the estimated percentages of participants at Week 24 that had had rescue therapy administered.
Trial Locations
- Locations (68)
Clinical Site 163
🇺🇸Baltimore, Maryland, United States
Clinical Site 145
🇺🇸Baltimore, Maryland, United States
Clinical Site 120
🇺🇸Cleveland, Ohio, United States
Clinical Site 149
🇺🇸Seattle, Washington, United States
Clinical Site 110
🇺🇸Miami, Florida, United States
Clinical Site 140
🇺🇸San Antonio, Texas, United States
Clinical Site 137
🇺🇸San Antonio, Texas, United States
Clinical Site 141
🇺🇸Detroit, Michigan, United States
Clinical Site 150
🇺🇸Phoenix, Arizona, United States
Clinical Site 138
🇺🇸Fresno, California, United States
Clinical Site 123
🇺🇸Peoria, Arizona, United States
Clinical Site 113
🇺🇸Encino, California, United States
Clinical Site 111
🇺🇸Beverly Hills, California, United States
Clinical Site 121
🇺🇸Pasadena, California, United States
Clinical Site 127
🇺🇸Pasadena, California, United States
Clinical Site 142
🇺🇸Rancho Cordova, California, United States
Clinical Site 116
🇺🇸Riverside, California, United States
CinCor Site 171
🇺🇸Torrance, California, United States
Clinical Site 160
🇺🇸Walnut Creek, California, United States
Clinical Site 106
🇺🇸Fort Lauderdale, Florida, United States
Clinical Site 131
🇺🇸Jacksonville, Florida, United States
Clinical Site 146
🇺🇸Oak Forest, Illinois, United States
Clinical Site 128
🇺🇸Springfield, Illinois, United States
Clinical Site 154
🇺🇸Indianapolis, Indiana, United States
Clinical Site 139
🇺🇸Lenexa, Kansas, United States
Clinical Site 167
🇺🇸Metairie, Louisiana, United States
Clinical Site 118
🇺🇸Albuquerque, New Mexico, United States
Clinical Site 101
🇺🇸Reno, Nevada, United States
Clinical Site 105
🇺🇸Bloomfield, New Jersey, United States
Clinical Site 136
🇺🇸Cherry Hill, New Jersey, United States
Clinical Site 114
🇺🇸Teaneck, New Jersey, United States
Clinical Site 109
🇺🇸Liverpool, New York, United States
Clinical Site 122
🇺🇸Edmond, Oklahoma, United States
Clinical Site 158
🇺🇸Springfield, Oregon, United States
Clinical Site 115
🇺🇸Kingston, Pennsylvania, United States
Clinical Site 130
🇺🇸Beaufort, South Carolina, United States
Clinical Site 133
🇺🇸Rapid City, South Dakota, United States
Clinical Site 102
🇺🇸Bellaire, Texas, United States
Clinical Site 108
🇺🇸Bellaire, Texas, United States
Clinical Site 126
🇺🇸McAllen, Texas, United States
Clinical Site 156
🇺🇸Houston, Texas, United States
Clinical Site 147
🇺🇸Burleson, Texas, United States
Clinical Site 132
🇺🇸Fort Worth, Texas, United States
Clinical Site 144
🇺🇸Texas City, Texas, United States
Clinical Site 159
🇺🇸Lynchburg, Virginia, United States
Clinical Site 201
🇵🇷Arecibo, Puerto Rico
Clinical Site 148
🇺🇸Spokane, Washington, United States
Clinical Site 168
🇺🇸Germantown, Tennessee, United States
Clinical Site 119
🇺🇸Nashville, Tennessee, United States
Clinical Site 169
🇺🇸Memphis, Tennessee, United States
Clinical Site 157
🇺🇸Coral Springs, Florida, United States
Clinical Site 129
🇺🇸Huntington Beach, California, United States
Clinical Site 153
🇺🇸Saint Petersburg, Florida, United States
Clinical Site 112
🇺🇸'Aiea, Hawaii, United States
Clinical Site 117
🇺🇸Winter Haven, Florida, United States
Clinical Site 151
🇺🇸Boston, Massachusetts, United States
Clinical Site 103
🇺🇸Hagerstown, Maryland, United States
Clinical Site 104
🇺🇸Boston, Massachusetts, United States
Clinical Site 155
🇺🇸Southaven, Mississippi, United States
Clinical Site 162
🇺🇸Rochester, New York, United States
Clinical Site 165
🇺🇸Raleigh, North Carolina, United States
Clinical Site 143
🇺🇸Beachwood, Ohio, United States
Clinical Site 152
🇺🇸Dublin, Ohio, United States
Clinical Site 164
🇺🇸Knoxville, Tennessee, United States
Clinical Site 161
🇺🇸Austin, Texas, United States
Clinical Site 125
🇺🇸Sacramento, California, United States
Clinical Site 166
🇺🇸Louisville, Kentucky, United States
Clinical Site 135
🇺🇸Portland, Oregon, United States