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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03780972




Registration number
NCT03780972
Ethics application status
Date submitted
14/12/2018
Date registered
19/12/2018
Date last updated
13/11/2019

Titles & IDs
Public title
A Study to Evaluate the Safety and Tolerability of ONL1204 in Patients With Macula-off, Rhegmatogenous Retinal Detachment
Scientific title
A Phase 1 Open-Label, Dose Escalation Study to Assess the Safety and Tolerability of Intravitreal ONL1204 in Patients With Macula-off, Rhegmatogenous Retinal Detachment
Secondary ID [1] 0 0
ONL1204-RRD-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rhegmatogenous Retinal Detachment - Macula Off 0 0
Condition category
Condition code
Eye 0 0 0 0
Diseases / disorders of the eye
Mental Health 0 0 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ONL1204
Treatment: Surgery - Intravitreal Injection
Treatment: Surgery - Collection of ocular fluids

Active Comparator: Cohort 1, 25 µg ONL1204 - Intravitreal injection of 50 µl of ONL1204 liquid formulation to deliver 25 µg of ONL1204 (0.5 mg/ml ONL1204 formulation)

Active Comparator: Cohort 2, 50 µg ONL1204 - Intravitreal injection of 100 µl of ONL1204 liquid formulation to deliver 50 µg of ONL1204 (0.5 mg/ml ONL1204 formulation)

Active Comparator: Cohort 3, 100 µg ONL1204 - Intravitreal injection of 50 µl of ONL1204 liquid formulation to deliver 100 µg of ONL1204 (2.0 mg/ml ONL1204 formulation)

Active Comparator: Cohort 4, 200 µg ONL1204 - Intravitreal injection of 100 µl of ONL1204 liquid formulation to deliver 200 µg of ONL1204 (2.0 mg/ml ONL1204 formulation)


Treatment: Drugs: ONL1204
Administration of ONL1204 - inhibitor of Fas(CD95) signaling by intravitreal injection

Treatment: Surgery: Intravitreal Injection
Injection of study drug into the eye

Treatment: Surgery: Collection of ocular fluids
vitreous and aqueous fluid collection by a tap and during vitrectomy

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Vital sign-systolic and diastolic blood pressure - Systolic and diastolic blood pressure in mmHg
Timepoint [1] 0 0
24 weeks
Primary outcome [2] 0 0
Vital sign-heart rate - Heart rate in beats per minute
Timepoint [2] 0 0
24 weeks
Primary outcome [3] 0 0
Best corrected visual acuity - ETDRS chart (number of letters read)
Timepoint [3] 0 0
24 weeks
Primary outcome [4] 0 0
Intraocular pressure - Intraocular pressure in mmHg
Timepoint [4] 0 0
24 weeks
Primary outcome [5] 0 0
Slit lamp biomicroscopy - Slit lamp biomicroscopy (using US FDA clinical grading scale 0-4; 0=normal, 4=very severe changes)
Timepoint [5] 0 0
24 weeks
Primary outcome [6] 0 0
Complete blood count - White blood cells with differential, hemoglobin, hematocrit and platelet count
Timepoint [6] 0 0
24 weeks

Eligibility
Key inclusion criteria
1. Males and females, = 18 to 80 years old

2. Able to give informed consent and comply with all study visits and procedures

3. Patients who:

1. Present between 1 week (7 days) and 4 weeks (28 days) of a macula-off RRD (based
on patient-reported history of loss of central vision)

2. For whom standard retinal reattachment surgery by means of a pars plana
vitrectomy (with or without scleral buckle) and gas tamponade is indicated, and

3. In the opinion of the investigator, can safely undergo all study procedures.

4. Best corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity of
20/100 to hand motion in the study eye

5. Best corrected ETDRS visual acuity in the fellow eye of 20/60 or better
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Presence of giant retinal tear defined as greater than 3 clock hours or other type of
complex retinal detachment in the study eye

2. Presence of vitreous hemorrhage in the study eye

3. Presence of ocular or periocular infection or intraocular inflammation in either eye

4. Intraocular Pressure > 22 mmHg in the study eye

5. Any other significant ocular disease in the study eye including media opacity that, in
the opinion of the investigator, would preclude a visual acuity of at least 20/25
following successful vitrectomy or limit adequate visibility of the retina

6. Any other ocular pathology in the study eye requiring treatment with topical
ophthalmic drops or intravitreal injection

7. History of previous ocular surgery in the study eye other than uncomplicated cataract
surgery with posterior chamber intraocular lens and intact posterior capsule (which
must have occurred at least 6 months prior to the baseline visit)

8. Participation in other clinical trials or use of any other investigational drugs or
devices within 3 months prior to study participation

9. Females who are pregnant or lactating and women of childbearing potential who are not
using adequate contraceptive precautions (e.g., intrauterine device, oral
contraceptives, barrier method, or other contraception deemed adequate by the
investigator)

10. Known retinopathy, known hepatic disease (or history of significant chronic liver
disease), or known renal disease. Patients with diabetes and no known retinopathy may
be enrolled

11. History of uncontrolled hypertension

12. History of stroke, transient ischemic attack, or major cardiac surgery within 3 months
prior to study, or current treatment for systemic infection

13. Any ocular or systemic condition that in the opinion of the investigator could
compromise the safety of the patient, or may interfere with the safety and
tolerability assessments or study procedures of the trial

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Save Sight Institute, Sydney Eye Hospital - Sydney
Recruitment postcode(s) [1] 0 0
2000 - Sydney

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
ONL Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the safety and tolerability of ONL1204 in
participants with Macula-off, Rhegmatogenous Retinal Detachment (RRD). RRD is an acute and
serious vision threatening condition in which a tear in the retina, typically resulting from
a vitreous detachment, allows liquid to accumulate under the retina, detaching the
photoreceptor (PR) layer of the retina from the retinal pigment epithelium (RPE). As the RPE
is the principal source of nutritional support for the PR layer, the photoreceptors begin a
cascade of inflammation and cell death. Photoreceptor cell death is the primary mechanism of
vision loss after retinal detachment.

ONL1204 is a first-in-class inhibitor of Fragment Apoptosis Stimulator receptor
(Fas)-mediated cell death. ONL1204 has demonstrated protection of multiple retinal cell types
in numerous preclinical models of acute ocular injury. This will be a first-in-human (FIH)
study to evaluate safety and tolerability of a single-dose of ONL1204 in participants with
macula-off RRD. The standard of care for surgical repair of macula-off RRD is reattachment
surgery within 7 days of the macula detaching. Participants in this study will receive a
single intravitreal injection upon diagnosis and enrollment in the study, followed by
standard of care surgery. The surgery includes vitrectomy, a procedure that removes the bulk
of drug remaining in the vitreous.
Trial website
https://clinicaltrials.gov/show/NCT03780972
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Matthew Simunovic, M.D.
Address 0 0
Save Sight Institute, Sydney Eye Hospital, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Jana van de Goor, Ph.D.
Address 0 0
Country 0 0
Phone 0 0
650-303-0094
Fax 0 0
Email 0 0
jvandegoor@onltherapeutics.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03780972