OTT166 in Diabetic Retinopathy (DR)

Sponsor

OcuTerra Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05409235

Collaborator

Parexel (Industry)

210

Enrollment

Locations

Arms

17.1

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Diabetic Retinopathy	Drug: OTT166 Drug: Vehicle control	Phase 2

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) and participants who do not have center-involved diabetic macular edema (CI-DME) will be randomized into the following groups:

OTT166 Cohort 1, OTT166 Cohort 2, Vehicle control Cohort 1, Vehicle control Cohort 2.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

210 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Jul 29, 2022

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OTT166 Cohort 1 Participants will receive OTT166 low dose for 24 weeks	Drug: OTT166 Participants will receive OTT166 ophthalmic solution
Experimental: OTT166 Cohort 2 Participants will receive OTT166 high dose for 24 weeks	Drug: OTT166 Participants will receive OTT166 ophthalmic solution
Placebo Comparator: Vehicle control Cohort 1 Participants will receive vehicle control for 24 weeks	Drug: Vehicle control Participants will receive vehicle control
Placebo Comparator: Vehicle control Cohort 2 Participants will receive vehicle control for 24 weeks	Drug: Vehicle control Participants will receive vehicle control

Outcome Measures

Primary Outcome Measures

Proportion of participants with treatment-emergent adverse events (TEAEs) [Upto end of the study (Week 24)]
To characterize the safety of topical OTT166 in participants with DR.
Proportion of participants who have 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. 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.

Secondary Outcome Measures

Proportion of participants developing worse than mild PDR (DRSS 65 and above) [At week 24]
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) and/or center-involved diabetic macular edema (CI-DME).
Proportion of participants who develop ASNV [At week 24]
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) and/or CI-DME.
Time to development of PDR worse than mild (DRSS 65 and above) [At week 24]
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) and/or CI-DME. Time to develop PDR worse than mild (DRSS 65 and above) will be assessed.
Proportion of participants who develop CI-DME [At week 24]
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) and/or CI-DME.
Time to development of CI-DME [At week 24]
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) and/or CI-DME. Time to develop CI-DME will be assessed.
Proportion of participants with change in DRSS steps [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.
Proportion of participants with mild PDR (DRSS score 61) at baseline who regress to NPDR (DRSS score ≤ 53) [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 from baseline in DRSS step [From Baseline (Day 1) up to 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.
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 will be assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) letters score. A higher score represents better functioning.
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) will be assessed.
Area under the curve (AUC) for change from baseline in 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 will be assessed by ETDRS letters score. A higher score represents better functioning.
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 will be assessed by optical coherence tomography (OCT).
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 will be assessed by OCT.
Proportion of participants who met the 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.
Time to meet rescue therapy 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. Time required to meet rescue therapy criteria will be assessed.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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]
BCVA ETDRS letter score in the study eye of ≥ 69 letters (approximate Snellen equivalent of 20/40 or better)
Treatment-naïve (ie, no previous anti-VEGF or steroid treatment or PRP or laser within 1,000 μm diameter of the foveal center/treatment for macular edema or DR in the study eye)

Exclusion Criteria:

Presence of diabetic macular edema (DME) threatening the center of the macula in the study eye
Any prior focal or grid laser photocoagulation or any prior PRP in the study eye
Eyes with DRSS score 61 due to fibrous proliferations at disc or fibrous proliferations elsewhere
Any prior systemic anti-VEGF intravitreal injection (IVT) or anti-VEGF treatment in the study eye
Any prior intraocular steroid injection in the study eye
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
Hypertension
Screening HbA1c blood test > 10.0%
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
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
Previous pars plana vitrectomy in the study eye
Any intraocular surgery in the study eye within 90 days (3 months) prior to study enrollment
Yttrium Aluminum Garnet (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
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
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
Women who are breastfeeding or who have a positive serum human chorionic gonadotropin (hCG)/urine pregnancy test at the screening or Baseline (BL) Visit
Ocular media of insufficient quality to obtain fundus photographs, fluorescein angiography, and optical coherence tomography (OCT) images in the study eye
CST of > 300 μm

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Site 123	Peoria	Arizona	United States	85381
2	Clinical Site 150	Phoenix	Arizona	United States	85021
3	Clinical Site 111	Beverly Hills	California	United States	90211
4	Clinical Site 113	Encino	California	United States	91436
5	Clinical Site 138	Fresno	California	United States	93720
6	Clinical Site 129	Huntington Beach	California	United States	92647
7	Clinical Site 121	Pasadena	California	United States	91105
8	Clinical Site 127	Pasadena	California	United States	91107
9	Clinical Site 142	Rancho Cordova	California	United States	95670
10	Clinical Site 116	Riverside	California	United States	92505
11	Clinical Site 125	Sacramento	California	United States	95841
12	Clinical Site 106	Fort Lauderdale	Florida	United States	33309
13	Clinical Site 131	Jacksonville	Florida	United States	32216
14	Clinical Site 110	Miami	Florida	United States	33143
15	Clinical Site 153	Saint Petersburg	Florida	United States	33711-1141
16	Clinical Site 117	Winter Haven	Florida	United States	33880
17	Clinical Site 112	'Aiea	Hawaii	United States	96701
18	Clinical Site 146	Oak Forest	Illinois	United States	60452
19	Clinical Site 128	Springfield	Illinois	United States	62704
20	Clinical Site 139	Lenexa	Kansas	United States	66215
21	Clinical Site 145	Baltimore	Maryland	United States	21287
22	Clinical Site 103	Hagerstown	Maryland	United States	21740
23	Clinical Site 151	Boston	Massachusetts	United States	02111
24	Clinical Site 104	Boston	Massachusetts	United States	02114
25	Clinical Site 141	Detroit	Michigan	United States	48201
26	Clinical Site 101	Reno	Nevada	United States	89502
27	Clinical Site 105	Bloomfield	New Jersey	United States	07003
28	Clinical Site 136	Cherry Hill	New Jersey	United States	08034
29	Clinical Site 114	Teaneck	New Jersey	United States	07666
30	Clinical Site 118	Albuquerque	New Mexico	United States	87109
31	Clinical Site 109	Liverpool	New York	United States	13088
32	Clinical Site 143	Beachwood	Ohio	United States	44122
33	Clinical Site 120	Cleveland	Ohio	United States	44122
34	Clinical Site 152	Dublin	Ohio	United States	43016
35	Clinical Site 122	Edmond	Oklahoma	United States	73013
36	Clinical Site 135	Portland	Oregon	United States	97239
37	Clinical Site 115	Kingston	Pennsylvania	United States	18704
38	Clinical Site 124	Philadelphia	Pennsylvania	United States	19107
39	Clinical Site 130	Beaufort	South Carolina	United States	29902
40	Clinical Site 133	Rapid City	South Dakota	United States	57701
41	Clinical Site 119	Nashville	Tennessee	United States	37203
42	Clinical Site 134	Austin	Texas	United States	78705
43	Clinical Site 102	Bellaire	Texas	United States	77401
44	Clinical Site 108	Bellaire	Texas	United States	77401
45	Clinical Site 147	Burleson	Texas	United States	76028
46	Clinical Site 132	Fort Worth	Texas	United States	76104
47	Clinical Site 126	McAllen	Texas	United States	78503
48	Clinical Site 140	San Antonio	Texas	United States	78240-1375
49	Clinical Site 137	San Antonio	Texas	United States	78240
50	Clinical Site 144	Texas City	Texas	United States	78240
51	Clinical Site 149	Seattle	Washington	United States	98125
52	Clinical Site 148	Spokane	Washington	United States	98204
53	Clinical Site 201	Arecibo		Puerto Rico	00612