Nesvategrast (OTT166) in Diabetic Retinopathy (DR)

NCT ID: NCT05409235

Last Updated: 2024-08-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 225 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-29
• Study Completion Date: 2023-12-29

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.

Conditions

Diabetic Retinopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

OTT166 Cohort 1

Participants will receive OTT166 5% twice a day (BID) for 24 weeks

Group Type: EXPERIMENTAL

OTT166

Intervention Type: DRUG

Participants will receive OTT166 ophthalmic solution

OTT166 Cohort 2

Participants will receive OTT166 5% four times a day (QID) for 24 weeks

Group Type: EXPERIMENTAL

OTT166

Intervention Type: DRUG

Participants will receive OTT166 ophthalmic solution

Vehicle control Cohort 1

Participants will receive vehicle control BID for 24 weeks

Group Type: PLACEBO_COMPARATOR

Vehicle control

Intervention Type: DRUG

Participants will receive vehicle control

Vehicle control Cohort 2

Participants will receive vehicle control QID for 24 weeks

Group Type: PLACEBO_COMPARATOR

Vehicle control

Intervention Type: DRUG

Participants will receive vehicle control

Interventions

OTT166

Participants will receive OTT166 ophthalmic solution

Intervention Type: DRUG

Vehicle control

Participants will receive vehicle control

Intervention Type: DRUG

Other Intervention Names

nesvategrast

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Parexel

INDUSTRY

Sponsor Role: collaborator

OcuTerra Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carl Regillo, MD

Role: PRINCIPAL_INVESTIGATOR

Principal Investigator

Locations

Clinical Site 123

Peoria, Arizona, United States

Clinical Site 150

Phoenix, Arizona, United States

Clinical Site 111

Beverly Hills, California, United States

Clinical Site 113

Encino, California, United States

Clinical Site 138

Fresno, California, United States

Clinical Site 129

Huntington Beach, 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

Clinical Site 125

Sacramento, California, United States

CinCor Site 171

Torrance, California, United States

Clinical Site 160

Walnut Creek, California, United States

Clinical Site 157

Coral Springs, Florida, United States

Clinical Site 106

Fort Lauderdale, Florida, United States

Clinical Site 131

Jacksonville, Florida, United States

Clinical Site 110

Miami, Florida, United States

Clinical Site 153

St. Petersburg, Florida, United States

Clinical Site 117

Winter Haven, Florida, United States

Clinical Site 112

‘Aiea, Hawaii, 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 166

Louisville, Kentucky, United States

Clinical Site 167

Metairie, Louisiana, United States

Clinical Site 163

Baltimore, Maryland, United States

Clinical Site 145

Baltimore, Maryland, United States

Clinical Site 103

Hagerstown, Maryland, United States

Clinical Site 151

Boston, Massachusetts, United States

Clinical Site 104

Boston, Massachusetts, United States

Clinical Site 141

Detroit, Michigan, United States

Clinical Site 155

Southaven, Mississippi, 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 118

Albuquerque, New Mexico, United States

Clinical Site 109

Liverpool, New York, 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 120

Cleveland, Ohio, United States

Clinical Site 152

Dublin, Ohio, United States

Clinical Site 122

Edmond, Oklahoma, United States

Clinical Site 135

Portland, Oregon, 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 168

Germantown, Tennessee, United States

Clinical Site 164

Knoxville, Tennessee, United States

Clinical Site 169

Memphis, Tennessee, United States

Clinical Site 119

Nashville, Tennessee, United States

Clinical Site 161

Austin, Texas, United States

Clinical Site 102

Bellaire, Texas, United States

Clinical Site 108

Bellaire, Texas, United States

Clinical Site 147

Burleson, Texas, United States

Clinical Site 132

Fort Worth, Texas, United States

Clinical Site 156

Houston, Texas, United States

Clinical Site 126

McAllen, Texas, United States

Clinical Site 140

San Antonio, Texas, United States

Clinical Site 137

San Antonio, Texas, United States

Clinical Site 144

Texas City, Texas, United States

Clinical Site 159

Lynchburg, Virginia, United States

Clinical Site 149

Seattle, Washington, United States

Clinical Site 148

Spokane, Washington, United States

Clinical Site 201

Arecibo, , Puerto Rico

Countries

United States; Puerto Rico

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

OTT166-201

Identifier Type: -

Identifier Source: org_study_id