Efficacy and Safety Evaluation of OCS-01 (Dexamethasone) Eye Drops in Diabetic Macular Edema: A Phase 2/3 Double-Masked, Randomized, Multicenter Study
- Trial ID
- 2023-507208-30-00
- Protocol
- DX219
- Sponsor
- Oculis Operations S.a.r.l.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** and **safety** of OCS-01 eye drops in subjects with **Diabetic Macular Edema (DME)**. This is conducted in two stages: Stage 1 aims to select an optimal dosing regimen for OCS-01, while Stage 2 focuses on comparing the efficacy and safety of OCS-01 against a vehicle at Week 52. The clinical relevance of this study lies in its potential to provide a new therapeutic option for managing DME, a condition that can lead to significant visual impairment in diabetic patients. No secondary objectives are specified for this study.
Participants
The clinical trial involves a total of **155 participants** diagnosed with **Diabetic Macular Edema (DME)**. The study population comprises both male and female adults aged between 18 to 85 years. Participants were selected based on specific criteria, including a documented diagnosis of type 1 or type 2 diabetes mellitus. The trial includes individuals who are either treatment-naïve or have previously received anti-VEGF and corticosteroid intravitreal treatments, with specified washout periods required for those with prior treatments. Participants are required to have a Best Corrected Visual Acuity (BCVA) within a defined range in the study eye. The trial population includes individuals from a vulnerable population, and race and ethnicity data are collected according to National Institutes of Health criteria. Lifestyle factors such as diet and physical activity are not specified in the available data.
Plans and Procedures
The clinical trial is designed as a **randomized**, double-masked, two-stage, multicenter study to evaluate the efficacy and safety of OCS-01 eye drops in subjects with **Diabetic Macular Edema (DME)**. The trial is structured into two stages, with Stage 1 focusing on selecting a dosing regimen and Stage 2 assessing the efficacy and safety of the treatment compared to a vehicle at Week 52. The study is expected to last until January 2026, with participant recruitment having commenced in October 2021. The trial involves a maximum treatment period of 52 weeks, during which participants will be administered eye drops containing **dexamethasone**.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, visual acuity, and diabetes status. The inclusion criteria require participants to have a documented diagnosis of type 1 or type 2 diabetes mellitus, with specific visual acuity scores in the study and non-study eyes. Follow-up visits will occur at various intervals to monitor the primary and secondary endpoints, including changes in Best Corrected Visual Acuity (BCVA) and central subfield thickness (CST) as measured by spectral domain optical coherence tomography (SD-OCT). The end-of-study visit will conclude the participant's involvement, assessing the long-term efficacy and safety of the treatment.
Participant involvement is expected to last up to 52 weeks, with conditions for early termination including non-compliance with the study protocol, adverse events, or withdrawal of consent. The trial's primary endpoints focus on the mean change in BCVA ETDRS letter score at specific visits, while secondary endpoints include the proportion of subjects with significant gains in BCVA and changes in CST. The study is not categorized as low intervention, reflecting its comprehensive approach to evaluating the investigational product's impact on DME.
Treatment
The clinical trial involves the use of **OCS-01**, an investigational medication formulated as **eye drops, suspension** for **ocular use**. The active substance in OCS-01 is **dexamethasone**, a chemical compound known for its anti-inflammatory properties. The pharmaceutical form of OCS-01 is specifically designed for ocular administration, ensuring targeted delivery to the eye. The maximum daily dose of OCS-01 is 2.7 mg, with a total maximum dose of 548.1 mg over the course of the study. The treatment period extends up to 52 weeks, with the dosing schedule determined based on the study's stage 1 findings. Participant compliance with the dosing regimen will be monitored throughout the trial to ensure adherence to the protocol.
In addition to the experimental treatment, a **placebo** is utilized as a comparator in the study. The placebo is also formulated as eye drops, suspension, and is administered via the same ocular route as OCS-01. This allows for a direct comparison of the efficacy and safety of OCS-01 against a non-active treatment. The placebo is designed to be indistinguishable from the investigational product in appearance and administration, ensuring the double-masked nature of the trial is maintained. Compliance with the placebo administration will be monitored similarly to the experimental treatment to maintain the integrity of the study results.
Efficacy
The efficacy of OCS-01 eye drops in subjects with **Diabetic Macular Edema** (DME) will be assessed through a two-stage, double-masked, randomized, multicenter clinical trial. The primary efficacy endpoint for Stage 1 is the mean change in Best Corrected Visual Acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letters score at Visit 5 (Week 6) compared with baseline. For Stage 2, the primary efficacy endpoint is the mean change in BCVA ETDRS letter score at Visit 12 (Week 52) compared with baseline.
Secondary efficacy endpoints include the proportion of subjects with a 3-line or greater gain in BCVA assessed with the ETDRS scale at specified visits, and the area under the curve (AUC) of BCVA ETDRS letter changes across postbaseline visits. Additionally, mean changes in central subfield thickness (CST) as measured by Spectral Domain Optical Coherence Tomography (SD-OCT) will be evaluated at various timepoints, including Visit 5 (Week 6), Visit 7 (Week 12), and Visit 12 (Week 52) compared with baseline. The assessments will be conducted using validated scales and imaging techniques to ensure accuracy and reliability of the data collected throughout the trial.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Stage 1- 1) Have a signed informed consent form before any study-specific procedures are performed
- Stage 2- 2) Be a male or female adult subject age 18 to 85 years.
- Stage 2- 3) DME with presence of intraretinal and/or subretinal fluid in the study eye, with CST of ≥310 µm by SD-OCT at screening (Visit 1) (to be confirmed by CRC); CST is not part of the eligibility reconfirmation on Day 1 (Visit 2).
- Stage 2- 4) BCVA ETDRS letters score >35 letters (>20/200 Snellen equivalent) in the non-study eye at screening (ie, as per definition of monocular blindness).
- Stage 2- 5) BCVA ETDRS letters score ≤65 (Snellen 20/50) and ≥24 (Snellen 20/320) in the study eye at screening and baseline (Visit 1 and Visit 2).
- Stage 2- 6) Documented diagnosis of Type 1 or Type 2 diabetes mellitus and an HbA1c of ≤ 10.0% prior to Visit 1 (Screening) (Historic values of HbA1c taken up to 2 months before the screening visit will be permissible otherwise the study site will collect a sample for analysis at screening [Visit 1]).
- Stage 2- 7) Anti-VEGF and corticosteroid IVT treatment-naïve (ie, have not received previous treatment with any anti-VEGF and corticosteroid IVT) in the study eye, OR treated with anti-VEGF agents IVT and/or corticosteroids IVT in the study eye in the past and for whom the following washout periods before Day 1 apply: a. Anti-VEGF agents IVT: 3 months b. Periocular or IVT corticosteroids: i. Triamcinolone: 4 months ii. Biodegradable slow-release steroid IVT implant (eg, Ozurdex): 6 months iii. Nonbiodegradable slow-release steroid implant (eg, Iluvien, Retisert, Yutiq): 3 years
- Stage 1- 2) Be a male or female adult subject age 18 to 85 years. Race and ethnicity information will be collected based on National Institutes of Health criteria
- Stage 1- 3) Have DME with presence of intraretinal and/or subretinal fluid in the study eye, with central subfield thickness (CST) of ≥310μm (may be adjusted based on gender specific requirements) by Spectral domain optical coherence tomography (SD-OCT) at screening (V1) (as assessed by an independent reading center); CST is not part of the eligibility reconfirmation on Day 1
- Stage 1- 4) Participants require Best Corrected Visual Acuity (BCVA) ETDRS letter score >34 letters (>20/200 Snellen equivalent) in the non–study eye at screening (as per definition of monocular blindness)
- Stage 1- 5) Have an BCVA ETDRS letter score ≤ 65 (Snellen 20/50) and ≥ 24 (Snellen 20/320) in the study eye at screening and baseline (Visit 1 and Visit 2)
- Stage 1- 6) Have a documented diagnosis of type 1 or type 2 diabetes mellitus and a glycosylated hemoglobin A1c (HbA1c) of ≤ 12.0% (≤108 mmol/mol) at Visit 1 (Screening)
- Stage 1- 7) Participants who have been treated with any antivascular endothelial growth factor (VEGF) agents intravitreally (IVT) and/or corticosteroids periocular or IVT in the study eye in the past and for whom the following washout periods before Day 1 would apply: a. Anti-VEGF agents IVT: 3 months b. Periocular or IVT corticosteroids: i. Triamcinolone: 4 months; ii. Biodegradable slow-release steroid IVT implant (eg, Ozurdex): 6 Months; iii. Nonbiodegradable slow-release steroid implant (eg, Iluvien, Retisert, Yutiq): 3 years Clarification: For inclusion criteria 7 and 8, each subject must meet one criterion or the other
- Stage 1- 8)Participants who are anti-VEGF and corticosteroid IVT treatment-naïve (ie, have not received previous treatment with any anti-VEGF and corticosteroid IVT) in the study eye.
- Stage 2- 1) Have a signed informed consent form before any study-specific procedures are performed
- Stage 1- 9) Have a negative urine pregnancy test at Visit 1, if women of childbearing potential (WOCBP) those who have experienced menarche and who are not surgically sterilized [bilateral tubal ligation, hysterectomy or bilateral oophorectomy] or postmenopausal [12 months after last menses]) and must use adequate birth control throughout the study period (refer to Appendix 2 of the protocol).
- Stage 2- 8) Negative urine pregnancy test at Visit 1, if WOCBP (those who have experienced menarche and who are not surgically sterilized [bilateral tubal ligation, hysterectomy or bilateral oophorectomy] or postmenopausal [12 months after last menses]) and must use adequate birth control throughout the study period (refer to Section 18.2 Appendix 2 of the protocol).
Exclusion Criteria
- Have macular edema considered to be because of a cause other than Diabetic macular edema (DME). Note: an eye should not be considered eligible if: (1) the macular edema is considered to be related to ocular surgery such as cataract extraction;(2) clinical exam and/or OCT suggest that vitreoretinal interface abnormalities disease (eg, a taut posterior hyaloid or epiretinal membrane) is the primary cause of the macular edema, or (3) the macular edema is considered to be related to another condition such as age-related macular degeneration, uveitis, retinal vein occlusion, or drug toxicity. If the DME consists of circumscribed, focal leakage that the evaluating Investigator believes should be treated with laser and no other treatments, the eye is not eligible to be a study eye.
- History of glaucoma and/or steroid induced elevated IOP in either eye.
- Cup to disc ratio more than 0.5 in either eye.
- Subjects who plan to continue using contact lenses as a main source of vision correction during the study in the study eye.
- Subjects who plan to use cosmetic contact lenses in the study eye during the study.
- History of major intraocular ocular surgery within 3 months including cataract surgery in the study eye.
- Panretinal photocoagulation in the study eye; OR grid laser within 1000 microns of the foveal center in the study eye.
- Participants who are currently enrolled in or have participated in any other clinical study involving a study drug or device, or in any other type of medical research, within 30 days before screening and up to completion of the current study.
- Systemic corticosteroids (prednisone or methylprednisolone) either oral or injectable are not allowed in the study. The use of acute inhaled corticosteroids is permissible during the study for up to 14 days.
- Any prior or concomitant systemic anti-VEGF treatment within 6 months before Day 1.
- Significant medical conditions that in the opinion of the Investigator may affect the subject compliance with study visits.
- Have a decrease in Best Corrected Visual Acuity (BCVA) because of causes other than DME (eg, foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, previous vitreoretinal surgery, central serous retinopathy, nonretinal condition, substantial cataract, macular ischemia) that, in the Investigator's opinion, is likely to be decreasing BCVA by 3 lines or more (ie, cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal) in the study eye.
- Female participants must not be pregnant or breastfeeding.
- WOCBP who are not able to comply with adequate birth control throughout the study period.
- History of chronic renal failure that requires dialysis or kidney transplant.
- Stage 2- 1) Macular edema considered to be because of a cause other than DME. Examples included the macular edema is considered to be related to ocular surgery, clinical exam and/or OCT suggest that vitreoretinal interface abnormalities disease, acute macular degeneration (AMD), retinal vein occlusion (RVO), uveitis.
- Have a known history of significant macular ischemia which would prevent gain in visual acuity in the study eye.
- Have any other ocular disease that may cause substantial reduction in BCVA, including, retinal detachment, epiretinal membrane, vitreous hemorrhage or fibrosis involving the macula in the study eye, ocular inflammation (uveitis), other retinal inflammatory or infectious diseases.
- Have active or suspected periocular or ocular infection in the study eye (eg, keratitis, scleritis, or conjunctivitis). Mild noninfectious blepharitis is accepted.
- Have a history of noninfectious uveitis in the study eye.
- History of herpetic ocular disease in the study eye.
- Hazy ocular media in the study eye, as assessed by the Investigator, that may affect fundus examination and OCT measurements.
- Intraocular pressure (IOP) more than 21 mm Hg at Screening in the study eye (glaucoma suspects).
- Stage 2- 2) Decrease in BCVA because of causes other than DME.
- Stage 2- 3) Known history of significant macular ischemia which would prevent gain in visual acuity in the study eye.
- Stage 2- 4) Any other ocular disease in the study eye that may cause substantial reduction in BCVA, including retinal detachment, vitreomacular traction, epiretinal membrane, vitreous hemorrhage or fibrosis involving the macula, ocular inflammation (uveitis), other retinal inflammatory or infectious diseases.
- Stage 2- 5) Active or suspected periocular or ocular infection in the study eye. Mild noninfectious blepharitis is accepted.
- Stage 2- 6) History of noninfectious uveitis in the study eye.
- Stage 2- 7) Uncontrolled ocular hypertension or glaucoma in either eye, defined as IOP >22 mmHg while on more than 1 IOP-lowering medication at screening (Visit 1).
- Stage 2- 8) Subjects who plan to continue using contact lenses (including cosmetic contact lenses) during the study in the study eye.
- Stage 2- 9) Subjects with high-risk proliferative diabetic retinopathy (PDR) as per CRC assessment at screening (Visit 1) only.
- Stage 2- 10) Currently enrolled in or have participated in any other clinical study involving a study drug or device, or in any other type of medical research, within 30 days before screening and up to completion of the current study.
- Stage 2- 11) Use of systemic corticosteroids (ie, oral, IM, IV, intranasal) within 1 month prior to screening (Visit 1) and no systemic corticosteroids anticipated throughout the study.
- Stage 2- 12) Any prior or concomitant systemic anti-VEGF treatment within 6 months prior to Day 1.
- Stage 2- 13) Any other medical condition that in the opinion of the investigator may affect BCVA, may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject’s participation in the study.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Hungary | Not Recruiting | 05 Oct 2021 | 25 |
 Spain | Not Recruiting | 05 Oct 2021 | 24 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Eye drops, suspension, ocular use | Placebo | N/A | — | — | — | N/A |