Clinical trial NCT05409235: Nesvategrast (OTT166) in Diabetic Retinopathy (DR)
Official title: OTT166-201 A Phase 2 Randomized, Double-Masked, Vehicle-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of OTT166 Ophthalmic Solution in the Treatment of Diabetic Retinopathy (DR)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Retinopathy
Keywords: Diabetic Retinopathy
Ophthalmic solution
Non-proliferative diabetic retinopathy
Proliferative diabetic retinopathy
Lead sponsor: OcuTerra Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2022-06-08
Enrollment: 225
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. 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
2. BCVA ETDRS letter score in the study eye of ≥ 69 letters (approximate Snellen equivalent of 20/40 or better)
3. Normal foveal contour
4. Treatment naïve (ie, no previous anti-VEGF or steroid treatment or PRP or laser)
5. Willing and able to return for all study visits and comply with study-related procedures
6. Able to adhere to the study dosing requirements
7. Understands and signs the written Informed Consent Form

Exclusion Criteria:

1. 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
2. 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)
3. 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
4. Any prior systemic anti-VEGF treatment or IVT anti-VEGF treatment in the study eye
5. 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
6. Current ASNV, vitreous hemorrhage, or tractional retinal detachment visible at the screening assessments in the study eye
7. Uncontrolled glaucoma or ocular hypertension in the study eye defined as an IOP \> 25 mmHg regardless of concomitant treatment with IOP-lowering medications
8. Hypertension defined as systolic \> 180 mmHg or \> 160 mmHg on 2 consecutive measurements (during the same visit) or diastolic \> 100 mmHg
9. Screening HbA1c blood test \> 12.0%
10. Renal failure (stage 4 or end-stage), dialysis, or history of renal transplant
11. 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
12. 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
13. Epiretinal membrane, posterior hyaloidal traction, and/or vitreomacular traction in the study eye as determined to be significant by the Investigator
14. Previous pars plana vitrectomy in the study eye
15. Any intraocular surgery in the study eye within 90 days (3 months) prior to study enrollment
16. YAG laser treatment in the study eye within 90 days prior to study enrollment
17. 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
18. Contact lens use from time of screening throughout the study
19. Central corneal changes from dry eye that are visually significant and/or Sjogren's syndrome
20. 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)
21. Chronic or recurrent uveitis in the study eye
22. Ongoing ocular infection or inflammation in either eye
23. A history of cataract surgery complicated by vitreous loss in the study eye
24. Congenital eye malformations in the study eye
25. A history of penetrating ocular trauma in the study eye
26. Cognitive impairment that, in the opinion of the investigator, could compromise compliance with the requirements of the study
27. 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
28. 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
29. 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
30. Contraindication to the study medications or fluorescein dye
31. Other ocular pathologies that, in the investigator's opinion, would interfere with the participant's vision in the study eye
32. Ocular media of insufficient quality to obtain fundus photographs, fluorescein angiography, and OCT images in the study eye
33. 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

Primary outcomes:
measure: Proportion of Participants Who Improved by ≥ 2 Steps From Baseline in Diabetic Retinopathy Severity Scale (DRSS) Scores
timeFrame: At week 24
Secondary outcomes:
measure: Proportion of Participants That Developed Worse Than Mild PDR (DRSS 65 and Above)
timeFrame: At week 24
measure: Proportion of Participants Who Developed ASNV
timeFrame: At week 24
measure: Development of PDR Worse Than Mild (Wtm) (DRSS 65 and Above)
timeFrame: At week 24
measure: Proportion of Participants Who Developed CI-DME
timeFrame: At week 24
measure: The Development of CI-DME
timeFrame: At week 24
measure: Proportion of Participants That Developed Visually Threatening Complications (VTC) Complications (VTC)
timeFrame: At Week 24
measure: Time to Development of PDR Worse Than Mild (DRSS 65 and Above) or CI-DME
timeFrame: From Baseline (Day 1) up to Week 24
measure: Proportion of Participants With Change in DRSS Steps at Week 24 Compared to Baseline
timeFrame: At week 24
measure: Proportion of Participants With Mild PDR at Baseline Who Regressed to NPDR
timeFrame: At week 24
measure: Change From Baseline in Best Corrected Visual Acuity (BCVA)
timeFrame: From Baseline (Day 1) up to Week 24
measure: Proportion of Participants With Lines Gained/Lost of BCVA
timeFrame: From Baseline (Day 1) up to Week 24
measure: Area Under the Curve for BCVA (ETDRS Letters) From Baseline to Week 24
timeFrame: From Baseline (Day 1) up to Week 24
measure: Change From Baseline in Central Subfield Thickness (CST)
timeFrame: From Baseline (Day 1) up to Week 24
measure: Area Under The Curve (AUC) for Change From Baseline in CST
timeFrame: From Baseline (Day 1) up to Week 24
measure: Proportion of Participants Who Met the Objective Rescue Criteria
timeFrame: From Baseline (Day 1) up to Week 24
measure: Proportion That Met Objective Rescue Therapy Criteria by Week 24
timeFrame: From Baseline (Day 1) up to Week 24
measure: Percentages of Participants at Week 24 That Had Had Rescue Therapy Administered
timeFrame: 24 Weeks
Other outcomes:
measure: Proportion of Participants That Develop a VTC by Week 24 for DRSS Levels 47 and 53 at Baseline
timeFrame: 24 weeks
measure: Proportion of Participants Who Developed CI-DME at Week 24 for Randomization Strata DRSS 47 and 53
timeFrame: 24 weeks
Locations:
city: Peoria
country: United States
facility: Clinical Site 123
state: Arizona
city: Phoenix
country: United States
facility: Clinical Site 150
state: Arizona
city: Beverly Hills
country: United States
facility: Clinical Site 111
state: California
city: Encino
country: United States
facility: Clinical Site 113
state: California
city: Fresno
country: United States
facility: Clinical Site 138
state: California
city: Huntington Beach
country: United States
facility: Clinical Site 129
state: California
city: Pasadena
country: United States
facility: Clinical Site 121
state: California
city: Pasadena
country: United States
facility: Clinical Site 127
state: California
city: Rancho Cordova
country: United States
facility: Clinical Site 142
state: California
city: Riverside
country: United States
facility: Clinical Site 116
state: California
city: Sacramento
country: United States
facility: Clinical Site 125
state: California
city: Torrance
country: United States
facility: CinCor Site 171
state: California
city: Walnut Creek
country: United States
facility: Clinical Site 160
state: California
city: Coral Springs
country: United States
facility: Clinical Site 157
state: Florida
city: Fort Lauderdale
country: United States
facility: Clinical Site 106
state: Florida
city: Jacksonville
country: United States
facility: Clinical Site 131
state: Florida
city: Miami
country: United States
facility: Clinical Site 110
state: Florida
city: Saint Petersburg
country: United States
facility: Clinical Site 153
state: Florida
city: Winter Haven
country: United States
facility: Clinical Site 117
state: Florida
city: 'Aiea
country: United States
facility: Clinical Site 112
state: Hawaii
city: Oak Forest
country: United States
facility: Clinical Site 146
state: Illinois
city: Springfield
country: United States
facility: Clinical Site 128
state: Illinois
city: Indianapolis
country: United States
facility: Clinical Site 154
state: Indiana
city: Lenexa
country: United States
facility: Clinical Site 139
state: Kansas
city: Louisville
country: United States
facility: Clinical Site 166
state: Kentucky
city: Metairie
country: United States
facility: Clinical Site 167
state: Louisiana
city: Baltimore
country: United States
facility: Clinical Site 163
state: Maryland
city: Baltimore
country: United States
facility: Clinical Site 145
state: Maryland
city: Hagerstown
country: United States
facility: Clinical Site 103
state: Maryland
city: Boston
country: United States
facility: Clinical Site 151
state: Massachusetts
city: Boston
country: United States
facility: Clinical Site 104
state: Massachusetts
city: Detroit
country: United States
facility: Clinical Site 141
state: Michigan
city: Southaven
country: United States
facility: Clinical Site 155
state: Mississippi
city: Reno
country: United States
facility: Clinical Site 101
state: Nevada
city: Bloomfield
country: United States
facility: Clinical Site 105
state: New Jersey
city: Cherry Hill
country: United States
facility: Clinical Site 136
state: New Jersey
city: Teaneck
country: United States
facility: Clinical Site 114
state: New Jersey
city: Albuquerque
country: United States
facility: Clinical Site 118
state: New Mexico
city: Liverpool
country: United States
facility: Clinical Site 109
state: New York
city: Rochester
country: United States
facility: Clinical Site 162
state: New York
city: Raleigh
country: United States
facility: Clinical Site 165
state: North Carolina
city: Beachwood
country: United States
facility: Clinical Site 143
state: Ohio
city: Cleveland
country: United States
facility: Clinical Site 120
state: Ohio
city: Dublin
country: United States
facility: Clinical Site 152
state: Ohio
city: Edmond
country: United States
facility: Clinical Site 122
state: Oklahoma
city: Portland
country: United States
facility: Clinical Site 135
state: Oregon
city: Springfield
country: United States
facility: Clinical Site 158
state: Oregon
city: Kingston
country: United States
facility: Clinical Site 115
state: Pennsylvania
city: Beaufort
country: United States
facility: Clinical Site 130
state: South Carolina
city: Rapid City
country: United States
facility: Clinical Site 133
state: South Dakota
city: Germantown
country: United States
facility: Clinical Site 168
state: Tennessee
city: Knoxville
country: United States
facility: Clinical Site 164
state: Tennessee
city: Memphis
country: United States
facility: Clinical Site 169
state: Tennessee
city: Nashville
country: United States
facility: Clinical Site 119
state: Tennessee
city: Austin
country: United States
facility: Clinical Site 161
state: Texas
city: Bellaire
country: United States
facility: Clinical Site 102
state: Texas
city: Bellaire
country: United States
facility: Clinical Site 108
state: Texas
city: Burleson
country: United States
facility: Clinical Site 147
state: Texas
city: Fort Worth
country: United States
facility: Clinical Site 132
state: Texas
city: Houston
country: United States
facility: Clinical Site 156
state: Texas
city: McAllen
country: United States
facility: Clinical Site 126
state: Texas
city: San Antonio
country: United States
facility: Clinical Site 140
state: Texas
city: San Antonio
country: United States
facility: Clinical Site 137
state: Texas
city: Texas City
country: United States
facility: Clinical Site 144
state: Texas
city: Lynchburg
country: United States
facility: Clinical Site 159
state: Virginia
city: Seattle
country: United States
facility: Clinical Site 149
state: Washington
city: Spokane
country: United States
facility: Clinical Site 148
state: Washington
city: Arecibo
country: Puerto Rico
facility: Clinical Site 201
Study officials:
affiliation: Principal Investigator
name: Carl Regillo, MD
role: PRINCIPAL_INVESTIGATOR
References: