Clinical Trials Register

Summary
EudraCT Number:	2021-005173-95
Sponsor's Protocol Code Number:	DX219
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-07-01
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2021-005173-95

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.4.1

Sponsor's protocol code number

DX219

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT05066997

A.5.4

Other Identifiers

Name:

IND

Number:

131596

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Oculis SA
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Oculis SA
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Oculis SA
B.5.2	Functional name of contact point	Bastian Dehmel
B.5.3	Address:
B.5.3.1	Street Address	EPFL Innovation Park Building D
B.5.3.2	Town/ city	Lausanne
B.5.3.3	Post code	1015
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+4121711 3970
B.5.6	E-mail	info@oculis.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Dexamethasone ophthalmic suspension 1.5% (15 mg/mL)
D.3.2	Product code	OCS-01
D.3.4	Pharmaceutical form	Eye drops, suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Ocular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Dexamethasone
D.3.9.2	Current sponsor code	OCS-01
D.3.9.4	EV Substance Code	SUB07017MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/V) percent weight/volume
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Eye drops, suspension
D.8.4	Route of administration of the placebo	Ocular use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Diabetic Macular Edema (DME)

E.1.1.1

Medical condition in easily understood language

Diabetic Macular Edema (DME)

E.1.1.2

Therapeutic area

Body processes [G] - Ocular Physiological Phenomena [G14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10057934
E.1.2	Term	Diabetic macular edema
E.1.2	System Organ Class	100000004853

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Stage 1:
To evaluate the safety and efficacy of OCS-01 versus Vehicle alone in subjects with diabetic macular edema (DME).
These subjects will not be included in Stage 2 evaluations.

Stage 2:
To confirm the efficacy and safety of OCS-01 in subjects with DME.

E.2.2

Secondary objectives of the trial

Not Applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion Criteria for Stage 1
1) Have a signed informed consent form before any study-specific procedures are performed.
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.
3) Have DME with presence of intraretinal and/or subretinal fluid in the study eye, with central subfield thickness (CST) of ≥310 μm (may be adjusted based on gender specific requirements) by Spectral domain optical coherence tomography (SD-OCT) at screening (Visit 1) (as assessed by an independent reading center); CST is not part of the eligibility reconfirmation on Day 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 (ie, as per definition of monocular blindness).
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).
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).

Clarification: For inclusion criteria 7 and 8, each subject must meet one criterion or the other.
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.
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.
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 5 of the protocol).

Inclusion Criteria for Stage 2
1) Have a signed informed consent form before any study-specific procedures are performed.
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.
3) Have DME with presence of intraretinal and/or subretinal fluid in the study eye, with CST of ≥310 μm (may be adjusted based on gender specific requirements) by SD-OCT at screening (Visit 1) (as assessed by an independent reading center); CST is not part of the eligibility reconfirmation on Day 1.
4) Participants require BCVA ETDRS letters score >34 letters (>20/200 Snellen equivalent) in the non–study eye at screening (ie, as per definition of monocular blindness).
5) Have a 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) Have a documented diagnosis of type 1 or type 2 diabetes mellitus and a HbA1c of ≤ 12.0% (≤108 mmol/mol) at Visit 1 (Screening).
Clarification: For inclusion criteria 7 and 8, each subject must meet one criterion or the other.
7) Participants who have been treated with any anti- VEGF agents 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.
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.
9) Have a 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 Appendix 5 of the protocol).

E.4

Principal exclusion criteria

Exclusion Criteria Stage 1

OCULAR
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) 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).
3) Have a known history of significant macular ischemia which would prevent gain in visual acuity in the study eye.
4) 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.
5) Have active or suspected periocular or ocular infection in the study eye (eg, keratitis, scleritis, or conjunctivitis). Mild noninfectious blepharitis is accepted.
6) Have a history of noninfectious uveitis in the study eye.
7) History of herpetic ocular disease in the study eye.
8) Hazy ocular media in the study eye, as assessed by the Investigator, that may affect fundus examination and OCT measurements.
9) Intraocular pressure (IOP) more than 21 mm Hg at Screening in the study eye (glaucoma suspects).
10) History of glaucoma and/or steroid induced elevated IOP in either eye.
11) Cup to disc ratio more than 0.5 in either eye.
12) Subjects who plan to continue using contact lenses as a main source of vision correction during the study in the study eye.
13) Subjects who plan to use cosmetic contact lenses in the study eye during the study.
14) History of major intraocular ocular surgery within 3 months including cataract surgery in the study eye.
15) Panretinal photocoagulation. Grid laser within 1000 microns of the foveal center.

SYSTEMIC
16) Participants who are currently enrolled in or have participated in any other clinical study involving an investigational product (IP) or device, or in any other type of medical research, within 30 days before screening and up to completion of the current study.
17) 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.
18) Any prior or concomitant systemic anti-VEGF treatment within 6 months before Day 1.
19) Significant medical conditions that in the opinion of the Investigator may affect the subject compliance with study visits.
20) Female participants must not be pregnant or breastfeeding.
21) WOCBP who are not able to comply with adequate birth control throughout the study period.
22) History of chronic renal failure that requires dialysis or kidney transplant.

Exclusion Criteria Stage 2
For Stage 2 Exclusion criteria, please refer to Clinical Study Protocol.

E.5 End points

E.5.1

Primary end point(s)

Stage 1
The primary efficacy endpoint for Stage 1 of this study is the mean change from baseline BCVA ETDRS letters score to Week 12 (Visit 7). The primary efficacy analysis for Stage 1 will be conducted in the ITT with intercurrent events handled as detailed for Stage 2 below.

Stage 2
The primary efficacy endpoint for Stage 2 in this study is the mean change from baseline BCVA ETDRS letters score to Week 52. The primary efficacy analyses will be conducted in the ITT with intercurrent events handled in the following manners:
1) Discontinuation of study drug and nonoptimal compliance will be ignored (that is, measured values will be used regardless of compliance or discontinuation of study drug) [treatment policy strategy].
2) Withdrawal because of AEs or lack of efficacy [assumed to be missing not at random (MNAR)]: missing data after withdrawal will be imputed employing multiple imputations using Vehicle treatment group-based regression methodology, regardless of randomized treatment group is used to impute missing data [hypothetical strategy].
3) Missing data without withdrawal or withdrawal because of reasons other than lack of efficacy or AEs [assumed to be missing at random (MAR)]: missing data will be imputed employing multiple imputations using randomized treatment-based Markov Chain Monte Carlo methodology to impute nonmonotone missing and using regression methodology to impute monotone missing [hypothetical strategy].

E.5.1.1

Timepoint(s) of evaluation of this end point

Stage 1: Visit 7
Stage 2: Week 52

E.5.2

Secondary end point(s)

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.

E.5.2.1

Timepoint(s) of evaluation of this end point

At week 52

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

United States

Spain

Hungary

Slovakia

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

241

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

241

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

184

F.4.2.2

In the whole clinical trial

482

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-09-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-08-09

P. End of Trial
P.	End of Trial Status	Ongoing

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