A Phase 2/3 Double-masked, Randomized, 2-stage, Multicenter Study of the Efficacy and Safety of OCS-01 Eye Drops in Subjects With Diabetic Macular Edema

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oculis Operations S.a.r.l.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Ocular Physiological Phenomena [G14]

Trial duration

20 Sep 2022 → 29 Jul 2024

Decision date (initial)

2023-09-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Oculis Operations Sarl, Switzerland

External identifiers

EU CT number

2023-507208-30-00

EudraCT number

2021-005173-95

ClinicalTrials.gov

NCT05066997

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Efficacy

Stage 1:
To select a dosing regimen for OCS-01 in subjects with diabetic macular edema (DME).
Stage 2:
To evaluate the efficacy and safety of OCS-01 as compared to Vehicle at Week 52 in subjects with DME.

Conditions and MedDRA coding

Diabetic Macular Edema (DME)

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Federal Institute For Drugs And Medical Devices, European Medicines Agency, Swedish Medical Products Agency

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Stage 1- 1) Have a signed informed consent form before any study-specific procedures are performed
2. Stage 2- 2) Be a male or female adult subject age 18 to 85 years.
3. 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).
4. 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).
5. 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).
6. 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]).
7. 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
8. 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
9. 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
10. 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)
11. 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)
12. 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)
13. 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
14. 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.
15. Stage 2- 1) Have a signed informed consent form before any study-specific procedures are performed
16. 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).
17. 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 35

1. 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.
2. History of glaucoma and/or steroid induced elevated IOP in either eye.
3. Cup to disc ratio more than 0.5 in either eye.
4. Subjects who plan to continue using contact lenses as a main source of vision correction during the study in the study eye.
5. Subjects who plan to use cosmetic contact lenses in the study eye during the study.
6. History of major intraocular ocular surgery within 3 months including cataract surgery in the study eye.
7. Panretinal photocoagulation in the study eye; OR grid laser within 1000 microns of the foveal center in the study eye.
8. 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.
9. 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.
10. Any prior or concomitant systemic anti-VEGF treatment within 6 months before Day 1.
11. Significant medical conditions that in the opinion of the Investigator may affect the subject compliance with study visits.
12. 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.
13. Female participants must not be pregnant or breastfeeding.
14. WOCBP who are not able to comply with adequate birth control throughout the study period.
15. History of chronic renal failure that requires dialysis or kidney transplant.
16. 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.
17. Have a known history of significant macular ischemia which would prevent gain in visual acuity in the study eye.
18. 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.
19. Have active or suspected periocular or ocular infection in the study eye (eg, keratitis, scleritis, or conjunctivitis). Mild noninfectious blepharitis is accepted.
20. Have a history of noninfectious uveitis in the study eye.
21. History of herpetic ocular disease in the study eye.
22. Hazy ocular media in the study eye, as assessed by the Investigator, that may affect fundus examination and OCT measurements.
23. Intraocular pressure (IOP) more than 21 mm Hg at Screening in the study eye (glaucoma suspects).
24. Stage 2- 2) Decrease in BCVA because of causes other than DME.
25. Stage 2- 3) Known history of significant macular ischemia which would prevent gain in visual acuity in the study eye.
26. 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.
27. Stage 2- 5) Active or suspected periocular or ocular infection in the study eye. Mild noninfectious blepharitis is accepted.
28. Stage 2- 6) History of noninfectious uveitis in the study eye.
29. 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).
30. Stage 2- 8) Subjects who plan to continue using contact lenses (including cosmetic contact lenses) during the study in the study eye.
31. Stage 2- 9) Subjects with high-risk proliferative diabetic retinopathy (PDR) as per CRC assessment at screening (Visit 1) only.
32. 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.
33. 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.
34. Stage 2- 12) Any prior or concomitant systemic anti-VEGF treatment within 6 months prior to Day 1.
35. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Stage 1: The primary efficacy endpoint for Stage 1 of this study 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.
2. Stage 2: The primary efficacy endpoint for Stage 2 in this study is the mean change in BCVA ETDRS letter score at Visit 12 (Week 52) compared with baseline.

Secondary endpoints 10

1. Stage 1: The proportion of subjects with a 3 line or greater gain in BCVA assessedwith ETDRS scale at Visit 5 (Week 6) compared with baseline.
2. Stage 1: • Area under the curve (AUC) of BCVA ETDRS letter changes across postbaseline visits up toWeek 6 and Week 12 compared with baseline.
3. Stage 1: • Mean change in BCVA ETDRS letters score at Visit 7 (Week 12)compared with baseline and Visit 5 (Week 6).
4. Stage 1: • The proportion of subjects with a 3 line or greater gain in BCVA assessed with ETDRS scale at Visit 7 (Week 12) compared with baseline and Visit 5 (Week 6).
5. Stage 1: • Mean change in CST as measured by SD-OCT at Visit 5 (Week 6) and Visit 7 (Week 12) compared with baseline, and at Visit 7 (Week 12) compared with Visit 5 (Week 6).
6. Stage 1: • The proportion of subjects with a 1-line or greater and a 2-line or greater gain in BCVA assessed with the ETDRS scale at each postbaseline visit.
7. Stage 1: • Mean change in CST as measured by SD--OCT compared with baseline at each postbaseline visit.
8. Stage 2: The proportion of subjects with a 3-line or greater gain in BCVA assessed with the ETDRS scale at Visit 9 (Week 52) compared with baseline. Please refer to Clinical Study Protocol for Other Secondary Efficacy Endpoints (section 7.1.5) for both Stages.
9. Other secondary efficacy endpoints: • AUC of BCVA ETDRS letter changes across postbaseline visits up to Visit 12 (Week 52). • Mean change in CST as measured by SD-OCT at Visit 12 (Week 52) compared with baseline. • Mean change in CST as measured by SD-OCT at each postbaseline visit compared with baseline.
10. Other secondary efficacy endpoints: • Mean change in BCVA ETDRS letters score at each postbaseline visit compared with baseline. • The proportion of subjects with a 3 line or greater gain in BCVA assessed with ETDRS scale at each postbaseline visit.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oculis Operations S.a.r.l.

Sponsor organisation

Oculis Operations S.a.r.l.

Address

Building D, Epfl Innovation Park Epfl Innovation Park

City

Lausanne

Postcode

1015

Country

Switzerland

Scientific contact point

Organisation

Oculis Operations S.a.r.l.

Contact name

Bastian Dehmel

Public contact point

Organisation

Oculis Operations S.a.r.l.

Contact name

Bastian Dehmel

Third parties 7

Locations

2 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

2 submissions — initial application plus substantial / non-substantial modifications