Nesvategrast (OTT166) in Diabetic Retinopathy (DR)

Diabetic Retinopathy Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05409235
• Other study ID #: OTT166-201
• Status: Completed
• Phase: Phase 2
• Start date: July 29, 2022
• Est. completion date: December 29, 2023

Study information

• Verified date: January 2024
• Source: OcuTerra Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the safety and efficacy of OTT166 Ophthalmic solution in participants with Diabetic Retinopathy.

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 into the following groups: OTT166 Cohort 1, OTT166 Cohort 2, Vehicle control Cohort 1, Vehicle control Cohort 2.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 225
• Est. completion date: December 29, 2023
• Est. primary completion date: December 29, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetic Retinopathy
• Retinal Diseases

Intervention

Drug:
• OTT166
Participants will receive OTT166 ophthalmic solution
• Vehicle control
Participants will receive vehicle control

Locations

Country	Name	City	State
Puerto Rico	Clinical Site 201	Arecibo
United States	Clinical Site 112	'Aiea	Hawaii
United States	Clinical Site 118	Albuquerque	New Mexico
United States	Clinical Site 161	Austin	Texas
United States	Clinical Site 145	Baltimore	Maryland
United States	Clinical Site 163	Baltimore	Maryland
United States	Clinical Site 143	Beachwood	Ohio
United States	Clinical Site 130	Beaufort	South Carolina
United States	Clinical Site 102	Bellaire	Texas
United States	Clinical Site 108	Bellaire	Texas
United States	Clinical Site 111	Beverly Hills	California
United States	Clinical Site 105	Bloomfield	New Jersey
United States	Clinical Site 104	Boston	Massachusetts
United States	Clinical Site 151	Boston	Massachusetts
United States	Clinical Site 147	Burleson	Texas
United States	Clinical Site 136	Cherry Hill	New Jersey
United States	Clinical Site 120	Cleveland	Ohio
United States	Clinical Site 157	Coral Springs	Florida
United States	Clinical Site 141	Detroit	Michigan
United States	Clinical Site 152	Dublin	Ohio
United States	Clinical Site 122	Edmond	Oklahoma
United States	Clinical Site 113	Encino	California
United States	Clinical Site 106	Fort Lauderdale	Florida
United States	Clinical Site 132	Fort Worth	Texas
United States	Clinical Site 138	Fresno	California
United States	Clinical Site 168	Germantown	Tennessee
United States	Clinical Site 103	Hagerstown	Maryland
United States	Clinical Site 156	Houston	Texas
United States	Clinical Site 129	Huntington Beach	California
United States	Clinical Site 154	Indianapolis	Indiana
United States	Clinical Site 131	Jacksonville	Florida
United States	Clinical Site 115	Kingston	Pennsylvania
United States	Clinical Site 164	Knoxville	Tennessee
United States	Clinical Site 139	Lenexa	Kansas
United States	Clinical Site 109	Liverpool	New York
United States	Clinical Site 166	Louisville	Kentucky
United States	Clinical Site 159	Lynchburg	Virginia
United States	Clinical Site 126	McAllen	Texas
United States	Clinical Site 169	Memphis	Tennessee
United States	Clinical Site 167	Metairie	Louisiana
United States	Clinical Site 110	Miami	Florida
United States	Clinical Site 119	Nashville	Tennessee
United States	Clinical Site 146	Oak Forest	Illinois
United States	Clinical Site 121	Pasadena	California
United States	Clinical Site 127	Pasadena	California
United States	Clinical Site 123	Peoria	Arizona
United States	Clinical Site 150	Phoenix	Arizona
United States	Clinical Site 135	Portland	Oregon
United States	Clinical Site 165	Raleigh	North Carolina
United States	Clinical Site 142	Rancho Cordova	California
United States	Clinical Site 133	Rapid City	South Dakota
United States	Clinical Site 101	Reno	Nevada
United States	Clinical Site 116	Riverside	California
United States	Clinical Site 162	Rochester	New York
United States	Clinical Site 125	Sacramento	California
United States	Clinical Site 153	Saint Petersburg	Florida
United States	Clinical Site 137	San Antonio	Texas
United States	Clinical Site 140	San Antonio	Texas
United States	Clinical Site 149	Seattle	Washington
United States	Clinical Site 155	Southaven	Mississippi
United States	Clinical Site 148	Spokane	Washington
United States	Clinical Site 128	Springfield	Illinois
United States	Clinical Site 158	Springfield	Oregon
United States	Clinical Site 114	Teaneck	New Jersey
United States	Clinical Site 144	Texas City	Texas
United States	CinCor Site 171	Torrance	California
United States	Clinical Site 160	Walnut Creek	California
United States	Clinical Site 117	Winter Haven	Florida

Sponsors (2)

Lead Sponsor	Collaborator
OcuTerra Therapeutics, Inc.	Parexel

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants with treatment-emergent adverse events (TEAEs)	To characterize the safety of topical OTT166 in participants with DR.	Upto end of the study (Week 24)
Primary	Proportion of participants who have improved by = 2 steps from baseline in Diabetic Retinopathy Severity Scale (DRSS) scores	To characterize the efficacy of topical OTT166 in participants with DR. Difference between treatments in proportion of participants achieving = 2 steps improvement from baseline as determined by central reading center assessment using the DRSS will be assessed. Greater DR scores confer a greater chance of converting to PDR. Higher scores are also associated with decreased vision-related quality of life measures.	At week 24
Secondary	Proportion of participants developing worse than mild PDR (DRSS 65 and above)	To determine if topical OTT166 will prevent or delay the occurrence of visually threatening complications (VTC). VTC is defined as the composite outcome of PDR (inclusive of participants who have vitreous hemorrhage or tractional retinal detachment believed to be due to PDR) and/or anterior segment neovascularization (ASNV) (participants with neovascularization of the iris [at least 2 cumulative clock hours], and/or definitive neovascularization of the iridocorneal angle).	At week 24
Secondary	Proportion of participants who develop ASNV	To determine if topical OTT166 will prevent or delay the occurrence of VTC. VTC is defined as the composite outcome of PDR (inclusive of participants who have vitreous hemorrhage or tractional retinal detachment believed to be due to PDR) and/or ASNV (participants with neovascularization of the iris [at least 2 cumulative clock hours], and/or definitive neovascularization of the iridocorneal angle).	At week 24
Secondary	Time to development of PDR worse than mild (DRSS 65 and above)	To determine if topical OTT166 will prevent or delay the occurrence of VTC. VTC is defined as the composite outcome of PDR (inclusive of participants who have vitreous hemorrhage or tractional retinal detachment believed to be due to PDR) and/or ASNV (participants with neovascularization of the iris [at least 2 cumulative clock hours], and/or definitive neovascularization of the iridocorneal angle). Time to develop PDR worse than mild (DRSS 65 and above) will be assessed.	At week 24
Secondary	Proportion of participants who develop CI-DME	To determine if topical OTT166 will prevent or delay 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.	At week 24
Secondary	Time to development of CI-DME	To determine if topical OTT166 will prevent or delay 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.	At week 24
Secondary	Proportion of participants developing visually threatening complications (VTC)	To determine if topical OTT166 will prevent or delay the occurrence of VTC. VTC is defined as the composite outcome of PDR and/or ASNV and/or CI-DME.	At Week 24
Secondary	Time to development of PDR worse than mild (DRSS 65 and above) or CI-DME	To determine if topical OTT166 will prevent or delay 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.	From Baseline (Day 1) up to Week 24
Secondary	Proportion of participants with change in DRSS steps	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.	At week 24
Secondary	Proportion of participants with mild PDR (DRSS score 61B) at baseline who regress to NPDR (DRSS score = 53)	To determine the effect of OTT166 on DRSS in participants with moderately severe to severe NPDR and mild PDR treated with topical OTT166.	At week 24
Secondary	Change from baseline in best corrected visual acuity (BCVA)	To determine the effect of OTT166 on BCVA in participants with moderately severe to severe NPDR and mild PDR. BCVA will be assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) letters score. A higher score represents better functioning.	From Baseline (Day 1) up to Week 24
Secondary	Proportion of participants with lines gained/lost of BCVA	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) will be assessed.	From Baseline (Day 1) up to Week 24
Secondary	Area under the curve (AUC) for change from baseline in BCVA	To determine the effect of OTT166 on BCVA in participants with moderately severe to severe NPDR and mild PDR. BCVA will be assessed by ETDRS letters score. A higher score represents better functioning.	From Baseline (Day 1) up to Week 24
Secondary	Change from baseline in central subfield thickness (CST)	To determine the effect of OTT166 on CST in participants with moderately severe to severe NPDR and mild PDR. CST will be assessed by optical coherence tomography (OCT).	From Baseline (Day 1) up to Week 24
Secondary	AUC for change from baseline in CST	To determine the effect of OTT166 on CST in participants with moderately severe to severe NPDR and mild PDR. CST will be assessed by OCT.	From Baseline (Day 1) up to Week 24
Secondary	Proportion of participants who met the objective rescue criteria	To determine the effect of OTT166 on the need for rescue therapy in participants with moderately severe to severe NPDR and mild PDR.	From Baseline (Day 1) up to Week 24
Secondary	Time to meet objective rescue therapy criteria	To determine the effect of OTT166 on the need for rescue therapy in participants with moderately severe to severe NPDR and mild PDR. Time required to meet rescue therapy criteria will be assessed.	From Baseline (Day 1) up to Week 24
Secondary	Time to administration of rescue therapy	To determine the effect of OTT166 on the need for rescue therapy in participants with moderately severe to severe NPDR and mild PDR. Time required to meet rescue therapy criteria will be assessed.	From Baseline (Day 1) up to Week 24