A Study to Evaluate the Efficacy and Safety of OTX-TKI (Axitinib Implant) in Participants With Non-Proliferative Diabetic Retinopathy (HELIOS-3)

March 12, 2026 updated by: Ocular Therapeutix, Inc.

A Phase 3, Multicenter, Double-Masked, Randomized, 3-Arm Parallel Group Study to Evaluate the Efficacy and Safety of Intravitreal OTXTKI (Axitinib Implant) in Participants With Non-Proliferative Diabetic Retinopathy

The purpose of this trial is to study the safety and effectiveness of OTX-TKI (axitinib intravitreal hydrogel) for the treatment of Non-Proliferative Diabetic Retinopathy.

OTX-TKI is an intravitreal hydrogel embedded with axitinib. When the OTX-TKI hydrogel is administered into the vitreous cavity of the eye, the hydrogel begins to slowly break down, which allows the axitinib to be slowly released over time.

This clinical trial is comparing OTX-TKI to a "sham" injection procedure. The sham injection is a mock injection procedure, but nothing will actually be inserted in the eye as there is no needle on the sham injector. Only one eye ("study eye") will be treated with study treatment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

930

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Maryland
      • Hagerstown, Maryland, United States, 21740
        • Recruiting
        • Cumberland Valley Retina Consultants
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male or female who is at least 18 years of age at the time of signing the informed consent form (ICF)
  2. History of or newly diagnosed with type 1 or 2 diabetes mellitus and have moderately severe to severe NPDR (DRSS levels 47 or 53), confirmed by the Central Reading Center (CRC) based on the images obtained at the Screening visit
  3. BCVA Early Treatment Diabetic Retinopathy Study (ETDRS) letter score of ≥ 69 letters (approximate Snellen equivalent of 20/40 or better) in the study eye
  4. Willing and able to comply with clinic visits and study-related procedures
  5. Provide signed informed consent

Exclusion Criteria:

  1. Presence of center-involved diabetic macular edema (CI-DME) defined per protocol via optical coherence tomography (SD-OCT) in the study eye, obtained at the Screening visit
  2. Evidence of a rhegmatogenous retinal detachment or visually significant/severe epiretinal membrane, vitreomacular traction syndrome, macular hole, tear of the retinal pigment epithelium in the macula, or other macular pathology in the study eye deemed visually significant by the Investigator
  3. In the study eye, any panretinal photocoagulation (PRP) treatment prior to baseline, or received focal or grid laser photocoagulation within 1000 microns of the central subfield of the macula within 6 months prior to baseline
  4. IVT anti-VEGF treatment in the study eye within 6 months or port delivery system (PDS) with ranibizumab in the study eye at any time prior to baseline (Day 1)
  5. (There are additional exclusion criteria)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: OTX-TKI Q52W (single dose)
OTX-TKI 0.45 mg via intravitreal (IVT) administration at Day 1 and sham procedure at Week 24
Drug: Single intravitreal injection of axitinib hydrogel implant followed by a mock (sham) injection procedure at Week 24
OTX-TKI 0.45 mg is a dried polyethylene glycol (PEG)-based hydrogel containing dispersed drug particles of the small molecule axitinib, a tyrosine kinase inhibitor (TKI).
Experimental: OTX-TKI Q24W (2 doses)
OTX-TKI 0.45 mg via IVT administration at Day 1 and Week 24
Drug: Intravitreal injection of axitinib hydrogel implant followed by a second intravitreal injection of the axitinib implant at Week 24
OTX-TKI 0.45 mg is a dried polyethylene glycol (PEG)-based hydrogel containing dispersed drug particles of the small molecule axitinib, a tyrosine kinase inhibitor (TKI).
Sham Comparator: Sham Q24W (control)
Sham procedure at Day 1 and Week 24
Other: Sham/mock procedure of intravitreal injection followed by a second sham/mock procedure at Week 24
sham/mock intravitreal injection procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
DRSS 2-step change status at Week 52 from baseline in the study eye (≥ 2 step improvement, ≥ 2-step worsening, < 2-step change in either direction)
Time Frame: 52 weeks
The Diabetic Retinopathy Severity Scale (DRSS) measures the severity of the diabetic retinopathy in patients by grading retinal images obtained by color fundus photography. Severity is determined by the presence of specific signs.
52 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ocular Therapeutix, Inc.

Investigators

  • Principal Investigator: Allen Hu, MD, Cumberland Valley Retina Consultants

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 17, 2025

Primary Completion (Estimated)

March 1, 2027

Study Completion (Estimated)

March 1, 2027

Study Registration Dates

First Submitted

November 14, 2025

First Submitted That Met QC Criteria

November 14, 2025

First Posted (Actual)

November 19, 2025

Study Record Updates

Last Update Posted (Actual)

March 16, 2026

Last Update Submitted That Met QC Criteria

March 12, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OTX-TKI-2025-NPDR-302

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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