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CompletedNCT03780972Updated Sep 24, 2024Results posted

A Study to Evaluate the Safety and Tolerability of ONL1204 in Patients With Macula-off, Rhegmatogenous Retinal Detachment

A Phase 1 interventional study of ONL1204 and Intravitreal Injection in Rhegmatogenous Retinal Detachment - Macula Off, sponsored by ONL Therapeutics. Completed at 4 sites in Australia. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2024-09-24.

Sponsored by ONL Therapeutics · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
14
Allocation
Non-randomized
Ages
18 Years to 80 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Rhegmatogenous Retinal Detachment - Macula Off

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03

In context

Retinal Detachment

199 studies on the registry are indexed under Retinal Detachment; 29 are open to participants now.

This study's enrollment of 14 is below the median of 50 across 132 interventional studies indexed under Retinal Detachment.

Browse Retinal Detachment studies →

Lead sponsor

ONL Therapeutics is the lead sponsor of 5 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Males and females, ≥ 18 to 80 years old
  2. Able to give 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

Exclusion criteria

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 drugs or devices within 3 months prior to study participation
  9. Females who are pregnant or lactating and women of who are not using adequate 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, , 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
Terms in these criteria, in plain language(5)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

TIA (transient ischaemic attack)

A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.

Stroke symptoms need emergency care at once, even if they go away.

05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
14 participants (actual)

Study arms

  • Active comparator
    Cohort 1 Dose A

    Intravitreal injection of 50 μl of ONL1204 liquid formulation to deliver dose 1

    Drug: ONL1204 · Procedure: Intravitreal Injection · Procedure: Collection of ocular fluids

  • Active comparator
    Cohort 2 Dose B

    Intravitreal injection of 100 μl of ONL1204 liquid formulation to deliver dose 2

    Drug: ONL1204 · Procedure: Intravitreal Injection · Procedure: Collection of ocular fluids

  • Active comparator
    Cohort 3 Dose C

    Intravitreal injection of 50 μl of ONL1204 liquid formulation to deliver dose 3

    Drug: ONL1204 · Procedure: Intravitreal Injection · Procedure: Collection of ocular fluids

  • Active comparator
    Cohort 4 Dose D

    Intravitreal injection of 100 μl of ONL1204 liquid formulation to deliver dose 4

    Drug: ONL1204 · Procedure: Intravitreal Injection · Procedure: Collection of ocular fluids

Interventions

  • DrugONL1204

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

  • ProcedureIntravitreal Injection

    Injection of study drug into the eye

  • ProcedureCollection of ocular fluids

    vitreous and aqueous fluid collection by a tap and during vitrectomy

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 24 weeks

  2. 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.

    Time frame: 24 weeks

Other outcomes

  1. Exploratory Outcome-ONL1204 Concentration

    Measurement of ONL1204 in plasma (ng/ml) after drug administration. For all subjects, the concentration was \<LLOQ.

    Time frame: 24 weeks

07

Results

Posted Sep 24, 2024

Participant flow

Participant flow — Overall Study
MilestoneCohort 1 Dose ACohort 2 Dose BCohort 3 Dose CCohort 4 Dose D
Started4442
Completed4442
Not completed0000

Outcome measures

PrimaryAdverse 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.

Time frame:
24 weeks
Reported as:
Count of participants · Participants
Adverse Event (AE) Reporting
ParticipantsCohort 1 Dose ACohort 2 Dose BCohort 3 Dose CCohort 4 Dose D
Adverse Event (AE) Reporting3332
PrimaryBCVA (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.

Time frame:
24 weeks
Reported as:
Mean · logMAR
BCVA (LogMAR) at Final Study Visit
logMARCohort 1 Dose ACohort 2 Dose BCohort 3 Dose CCohort 4 Dose D
BCVA (LogMAR) at Final Study Visit0.52 (0.2 to 0.7)0.50 (0.2 to 0.8)0.77 (0.5 to 1.3)0.46 (0.2 to 0.7)
Other pre-specifiedExploratory Outcome-ONL1204 Concentration

Measurement of ONL1204 in plasma (ng/ml) after drug administration. For all subjects, the concentration was \<LLOQ.

Time frame:
24 weeks
Reported as:
Mean · ng/ml
Exploratory Outcome-ONL1204 Concentration
ng/mlCohort 1 Dose ACohort 2 Dose BCohort 3 Dose CCohort 4 Dose D
Exploratory Outcome-ONL1204 ConcentrationNA ± NANA ± NANA ± NANA ± NA

Adverse events

Collected over 6 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cohort 1 Dose A0/4 (0%)0/4 (0%)3/4 (75%)
Cohort 2 Dose B0/4 (0%)2/4 (50%)3/4 (75%)
Cohort 3 Dose C0/4 (0%)2/4 (50%)3/4 (75%)
Cohort 4 Dose D0/2 (0%)0/2 (0%)2/2 (100%)
Most frequent serious events
Most frequent serious events
EventCohort 1 Dose ACohort 2 Dose BCohort 3 Dose CCohort 4 Dose D
Retinal Re-DetachmentEye disorders0/42/42/40/2
Intraocular InflammationEye disorders0/40/41/40/2
Most frequent other events
Showing 10 of 27
Most frequent other events
EventCohort 1 Dose ACohort 2 Dose BCohort 3 Dose CCohort 4 Dose D
Cataract or Worsening of CataractEye disorders0/41/42/40/2
Elevated Intraocular PressureEye disorders1/41/40/41/2
Covid-19 PositiveGeneral disorders0/40/40/41/2
FallInjury, poisoning and procedural complications0/40/40/41/2
Anterior UveitisEye disorders0/42/40/40/2
Ocular InflammationEye disorders0/40/41/41/2
Gel Like Substance in Vitreous CavityEye disorders0/40/40/41/2
Ocular pain post intravitreal injection/injuryEye disorders1/40/40/40/2
Redness/Ocular HyperaemiaEye disorders1/40/40/40/2
Nerve Fiber Lesions/OCT AbnormalitiesEye disorders1/40/40/40/2

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Cohort 1 Dose ACohort 2 Dose BCohort 3 Dose CCohort 4 Dose DTotal
<=18 years00000
Between 18 and 65 years13307
>=65 years31127
Age, Continuous
Age, Continuous(years)Cohort 1 Dose ACohort 2 Dose BCohort 3 Dose CCohort 4 Dose DTotal
Mean67.5 (62 to 70)54.5 (43 to 68)58 (43 to 84)67.5 (65 to 70)61 (43 to 84)
Sex: Female, Male
Sex: Female, Male(Participants)Cohort 1 Dose ACohort 2 Dose BCohort 3 Dose CCohort 4 Dose DTotal
Female02013
Male424111
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Cohort 1 Dose ACohort 2 Dose BCohort 3 Dose CCohort 4 Dose DTotal
Hispanic or Latino00000
Not Hispanic or Latino444214
Unknown or Not Reported00000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Cohort 1 Dose ACohort 2 Dose BCohort 3 Dose CCohort 4 Dose DTotal
American Indian or Alaska Native00000
Asian10102
Native Hawaiian or Other Pacific Islander00000
Black or African American00101
White342211
More than one race00000
Unknown or Not Reported00000
Region of Enrollment
Region of Enrollment(Participants)Cohort 1 Dose ACohort 2 Dose BCohort 3 Dose CCohort 4 Dose DTotal
Australia444214
08

Study locations

4 sites
  • Save Sight Institute, Sydney Eye Hospital
    Sydney, New South Wales 2000, Australia
  • Royal Adelaide
    Melbourne, Victoria 3002, Australia
  • Queensland Eye Institute
    Melbourne, Victoria 4101, Australia
  • Center for Eye Rearch Australia
    Melbourne, Victoria VIC 3002, Australia
09

References and documents

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: No

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Oct 2019 to primary completion in Aug 2021, 22 months.

Results were first posted in Sep 2024, 3 years 1 month after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Dec 14, 2018
First posted
Dec 19, 2018
StartActual
Oct 21, 2019
Primary completionActual
Aug 24, 2021
CompletionActual
Aug 24, 2022
Results first posted
Sep 24, 2024
Last update
Sep 24, 2024
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Sep 24, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03780972
Lead sponsor
ONL Therapeutics
Responsible party
Sponsor
First posted
Dec 19, 2018
Start date
Oct 21, 2019
Primary completion
Aug 24, 2021
Completion
Aug 24, 2022
Results posted
Sep 24, 2024
Last update
Sep 24, 2024

Study contacts

Matthew Simunovic, M.D.
principal investigator · Save Sight Institute, Sydney Eye Hospital, Australia

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Sep 2024. You cannot join it, but the record below documents what was studied.

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