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

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ClinicalTrials.gov Identifier: NCT03780972
Recruitment Status : Recruiting
First Posted : December 19, 2018
Last Update Posted : November 13, 2019
Sponsor:
Information provided by (Responsible Party):
ONL Therapeutics

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.


Condition or disease Intervention/treatment Phase
Rhegmatogenous Retinal Detachment - Macula Off Drug: ONL1204 Procedure: Intravitreal Injection Procedure: Collection of ocular fluids Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 21, 2019
Estimated Primary Completion Date : August 1, 2020
Estimated Study Completion Date : December 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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)
Drug: ONL1204
Administration of ONL1204 - inhibitor of Fas(CD95) signaling by intravitreal injection

Procedure: Intravitreal Injection
Injection of study drug into the eye

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

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

Procedure: Intravitreal Injection
Injection of study drug into the eye

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

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

Procedure: Intravitreal Injection
Injection of study drug into the eye

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

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

Procedure: Intravitreal Injection
Injection of study drug into the eye

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




Primary Outcome Measures :
  1. Vital sign-systolic and diastolic blood pressure [ Time Frame: 24 weeks ]
    Systolic and diastolic blood pressure in mmHg

  2. Vital sign-heart rate [ Time Frame: 24 weeks ]
    Heart rate in beats per minute

  3. Best corrected visual acuity [ Time Frame: 24 weeks ]
    ETDRS chart (number of letters read)

  4. Intraocular pressure [ Time Frame: 24 weeks ]
    Intraocular pressure in mmHg

  5. Slit lamp biomicroscopy [ Time Frame: 24 weeks ]
    Slit lamp biomicroscopy (using US FDA clinical grading scale 0-4; 0=normal, 4=very severe changes)

  6. Complete blood count [ Time Frame: 24 weeks ]
    White blood cells with differential, hemoglobin, hematocrit and platelet count


Other Outcome Measures:
  1. Exploratory outcome-ONL1204 concentration [ Time Frame: 24 weeks ]
    Measurement of ONL1204 in plasma and vitreous fluid (ng/ml) after drug administration

  2. Exploratory outcome-Analysis of cytokine panel concentration before and after drug administration [ Time Frame: 24 weeks ]
    A panel of cytokines will be measured by a single multiplex assay (in ng/ml) in the vitreous and aqueous samples before and after drug administration (monocyte chemoattractant protein-1 (MCP1), interferon gamma-induced protein 10 (IP10), fractalkine, macrophage inflammatory protein-1a (MIP1a), MIP1b, interleukins (IL2, IL1b, IL18, IL6, IL8, IL1ra, IL12p40, IL10, IL5), vesicular endothelial growth factor A (VEGFA), granulocyte colony stimulating factor (G-CSF), platelet derived growth factor-AB (PDGF-AB), tumor necrosis factor alpha (TNFa), intracellular adhesion molecule 1(ICAM1)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03780972


Contacts
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Contact: Jana van de Goor, Ph.D. 650-303-0094 jvandegoor@onltherapeutics.com
Contact: David Zacks, M.D./Ph.D. 734-936-0871 dnzacks@onltherapeutics.com

Locations
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Australia, New South Wales
Save Sight Institute, Sydney Eye Hospital Recruiting
Sydney, New South Wales, Australia, 2000
Contact: Matthew Simunovic, M.D.    +61 2 9382 7300      
Contact: Maria Williams    +61 2 9382 7300      
Sponsors and Collaborators
ONL Therapeutics
Investigators
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Principal Investigator: Matthew Simunovic, M.D. Save Sight Institute, Sydney Eye Hospital, Australia

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Responsible Party: ONL Therapeutics
ClinicalTrials.gov Identifier: NCT03780972     History of Changes
Other Study ID Numbers: ONL1204-RRD-001
First Posted: December 19, 2018    Key Record Dates
Last Update Posted: November 13, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Retinal Detachment
Dissociative Disorders
Mental Disorders
Retinal Diseases
Eye Diseases