Rhegmatogenous Retinal Detachment - Macula OffPhase 1NCT03780972
A Study to Evaluate the Safety and Tolerability of ONL1204 in Patients With Macula-off, Rhegmatogenous Retinal Detachment
A Phase 1 study testing ONL1204, Intravitreal Injection and Collection of ocular fluids in people with Rhegmatogenous Retinal Detachment - Macula Off, run by ONL Therapeutics at 4 sites in Australia.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Rhegmatogenous Retinal Detachment - Macula Off
- What is being tested?
- ONL1204, Intravitreal Injection and Collection of ocular fluids
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 4 sitesAustralia
- Study dates
- 21 Oct 2019to 24 Aug 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females, ≥ 18 to 80 years old
- Able to give informed consent and comply with all study visits and procedures
- Patients who:
- 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)
- For whom standard retinal reattachment surgery by means of a pars plana vitrectomy (with or without scleral buckle) and gas tamponade is indicated, and
- In the opinion of the investigator, can safely undergo all study procedures.
- Best corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity of 20/100 to hand motion in the study eye
- Best corrected ETDRS visual acuity in the fellow eye of 20/60 or better
Who cannot join
- Presence of giant retinal tear defined as greater than 3 clock hours or other type of complex retinal detachment in the study eye
- Presence of vitreous hemorrhage in the study eye
- Presence of ocular or periocular infection or intraocular inflammation in either eye
- Intraocular Pressure > 22 mmHg in the study eye
- 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
- Any other ocular pathology in the study eye requiring treatment with topical ophthalmic drops or intravitreal injection
Show all 13Show fewer
- 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)
- Participation in other clinical trials or use of any other investigational drugs or devices within 3 months prior to study participation
- 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)
- 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
- History of uncontrolled hypertension
- History of stroke, transient ischemic attack, or major cardiac surgery within 3 months prior to study, or current treatment for systemic infection
- 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
Trial locations and contacts
4 sites in 1 country.
Australia4 sites
Royal Adelaide
Melbourne, Victoria, 3002
Queensland Eye Institute
Melbourne, Victoria, 4101
Center for Eye Rearch Australia
Melbourne, Victoria, VIC 3002
Save Sight Institute, Sydney Eye Hospital
Sydney, New South Wales, 2000
About this study
Official 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
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.
- Being tested
- ONL1204, Intravitreal Injection, Collection of ocular fluids
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ONL1204Drug
Administration of ONL1204 - inhibitor of Fas(CD95) signaling by intravitreal injection
Intravitreal InjectionProcedure or surgery
Injection of study drug into the eye
Collection of ocular fluidsProcedure or surgery
vitreous and aqueous fluid collection by a tap and during vitrectomy
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 Dose A | Active comparator | Intravitreal injection of 50 μl of ONL1204 liquid formulation to deliver dose 1 Receives: Drug: ONL1204; Procedure: Intravitreal Injection; Procedure: Collection of ocular fluids |
| Cohort 2 Dose B | Active comparator | Intravitreal injection of 100 μl of ONL1204 liquid formulation to deliver dose 2 Receives: Drug: ONL1204; Procedure: Intravitreal Injection; Procedure: Collection of ocular fluids |
| Cohort 3 Dose C | Active comparator | Intravitreal injection of 50 μl of ONL1204 liquid formulation to deliver dose 3 Receives: Drug: ONL1204; Procedure: Intravitreal Injection; Procedure: Collection of ocular fluids |
| Cohort 4 Dose D | Active comparator | Intravitreal injection of 100 μl of ONL1204 liquid formulation to deliver dose 4 Receives: Drug: ONL1204; Procedure: Intravitreal Injection; Procedure: Collection of ocular fluids |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Event (AE) Reporting
AEs restricted to treatment-emergent AEs (TEAEs) only. Ocular and non-ocular AEs reported separately.
See AE Reporting Table for descriptive ocular and non-ocular AE findings.
Measured: 24 weeks
BCVA (LogMAR) at Final Study Visit
BCVA was performed in the study eye using ETDRS methodology and letters read were converted to a logMAR value using the following equation: logMAR = -0.02 × ETDRS + 1.7.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2018
- Study start21 Oct 2019
- Primary completion24 Aug 2021
- Study completion24 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Rhegmatogenous Retinal Detachment - Macula OffStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- ONL Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Matthew Simunovic, M.D., Principal investigator, Save Sight Institute, Sydney Eye Hospital, Australia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03780972
- Sponsor's protocol ID
- ONL1204-RRD-001
- Status last verified
- Sep 2024
- First submitted
- 14 Dec 2018
- Last updated
- 24 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT03780972
- Acronym / sponsor ID
- ONL1204-RRD-001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- ONL TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 21 Oct 2019 (actual)
- Primary completion
- 24 Aug 2021 (actual)
- Study completion
- 24 Aug 2022 (actual)
- First posted
- 19 Dec 2018 (actual)
- Results
- Posted 24 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 Dose A | Active comparator | Drug: ONL1204, Procedure: Intravitreal Injection, Procedure: Collection of ocular fluidsIntravitreal injection of 50 μl of ONL1204 liquid formulation to deliver dose 1 |
| Cohort 2 Dose B | Active comparator | Drug: ONL1204, Procedure: Intravitreal Injection, Procedure: Collection of ocular fluidsIntravitreal injection of 100 μl of ONL1204 liquid formulation to deliver dose 2 |
| Cohort 3 Dose C | Active comparator | Drug: ONL1204, Procedure: Intravitreal Injection, Procedure: Collection of ocular fluidsIntravitreal injection of 50 μl of ONL1204 liquid formulation to deliver dose 3 |
| Cohort 4 Dose D | Active comparator | Drug: ONL1204, Procedure: Intravitreal Injection, Procedure: Collection of ocular fluidsIntravitreal injection of 100 μl of ONL1204 liquid formulation to deliver dose 4 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Males and females, ≥ 18 to 80 years old
- Able to give informed consent and comply with all study visits and procedures
- Patients who:
- Best corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity of 20/100 to hand motion in the study eye
- Best corrected ETDRS visual acuity in the fellow eye of 20/60 or better
Key exclusion criteria (13 listed)
- Presence of giant retinal tear defined as greater than 3 clock hours or other type of complex retinal detachment in the study eye
- Presence of vitreous hemorrhage in the study eye
- Presence of ocular or periocular infection or intraocular inflammation in either eye
- Intraocular Pressure > 22 mmHg in the study eye
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ONL1204Administration of ONL1204 - inhibitor of Fas(CD95) signaling by intravitreal injection | Drug | Cohort 1 Dose A, Cohort 2 Dose B, Cohort 3 Dose C, Cohort 4 Dose D |
| Intravitreal InjectionInjection of study drug into the eye | Procedure or surgery | Cohort 1 Dose A, Cohort 2 Dose B, Cohort 3 Dose C, Cohort 4 Dose D |
| Collection of ocular fluidsvitreous and aqueous fluid collection by a tap and during vitrectomy | Procedure or surgery | Cohort 1 Dose A, Cohort 2 Dose B, Cohort 3 Dose C, Cohort 4 Dose D |
Primary outcome
Adverse Event (AE) Reporting
Time frame: 24 weeks
AEs restricted to treatment-emergent AEs (TEAEs) only. Ocular and non-ocular AEs reported separately. See AE Reporting Table for descriptive ocular and non-ocular AE findings.
BCVA (LogMAR) at Final Study Visit
Time frame: 24 weeks
BCVA was performed in the study eye using ETDRS methodology and letters read were converted to a logMAR value using the following equation: logMAR = -0.02 × ETDRS + 1.7.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthew Simunovic, M.D. principal investigator
Save Sight Institute, Sydney Eye Hospital, Australia
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ONL1204, Intravitreal Injection and Collection of ocular fluids in people with Rhegmatogenous Retinal Detachment - Macula Off, run by ONL Therapeutics at 4 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Event (AE) Reporting (time frame: 24 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2024.