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IschemiaPhase 1RAVE2NCT01225146

Study of 2.0 mg Ranibizumab in Subjects With Ischemic Central Retinal Vein Occlusion (RAVE2)

A Phase 1 study testing ranibizumab in people with Ischemia and Retinal Vein Occlusion, run by David M. Brown, M.D. at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The RAVE 2 trial is a phase I, open label, 12-month trial of intravitreal ranibizumab 2.0 mg in patients with ischemic CRVO who have been either previously treated with ranibizumab or treatment naïve. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
What is being tested?
ranibizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteUnited States
Study dates
Oct 2010to Aug 2012
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 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Subjects will be eligible if the following criteria are met:
  • Ability to provide written informed consent and comply with study assessments for the full duration of the study
  • Age > 18 years
  • For patients previously treated with ITV ranibizumab (Cohort 1):
  • 6 or more intravitreal injections of ranibizumab with presence of persistent edema after a minimum of 6 ranibizumab injections followed in RAVE 1.
  • For treatment naïve (Cohort 2):
Show all 13Show fewer
  • Ischemic CRVO within 3 months of enrollment as per the following inclusion criteria
  • Three of the following clinical tests must be present to demonstrate ischemic CRVO:
  • VA 20/200 or worse
  • RAPD 0.9 LU or worse
  • Loss of 1-2e isopter on Goldmann Visual field (Kwon et al. 2001)
  • ERG demonstrating b wave amplitude less than 60% of A wave
  • Capillary nonperfusion greater than 50 DA

Who cannot join

  • Subjects who meet any of the following criteria will be excluded from this study:
  • IOP over 30 mm Hg
  • Any previous retinal laser photocoagulation to the study eye in treatment naive
  • Any previous intravitreal injection in study eye (triamcinolone or other) in treatment naive
  • Any previous vitrectomy in study eye (posterior or anterior associated with vitreous loss in cataract surgery)
  • Intracapsular cataract extraction (posterior capsule needs to be present)
Show all 37Show fewer
  • Previous history of retinal detachment in study eye
  • Any previous radiation treatments to head/ neck
  • Inability to assess iris neovascularization (corneal opacity precluding gonioscopy)
  • Significant cardiovascular disease or cancer that would prevent follow-up visits or completion of the 12 month study
  • Significant diabetic retinopathy in the fellow eye (diabetic macular edema, proliferative diabetic retinopathy, or high-risk non-proliferative diabetic retinopathy)
  • Pregnancy (positive pregnancy test)
  • Participation in another simultaneous medical investigator or trial
  • Ocular disorders in the study eye that may confound interpretation of study results, including retinal detachment, macular hole, or choroidal neovascularization of any cause (e.g., DME AMD, ocular histoplasmosis, or pathologic myopia)
  • Concurrent disease in the study eye that could compromise visual acuity or require medical or surgical intervention during the study period
  • Aphakia or absence of the posterior capsule in the study eye
  • Previous violation of the posterior capsule is also excluded unless it occurred as a result of YAG laser posterior capsulotomy in association with prior, posterior chamber intraocular lens implantation
  • History of idiopathic or autoimmune uveitis in either eye
  • Structural damage to the center of the macula in the study eye preexisting to CRVO likely to preclude improvement in visual acuity following the resolution of macular edema, including atrophy of the retinal pigment epithelium, subretinal fibrosis, laser scar(s)
  • Vitreomacular traction or epiretinal membrane in the study eye evident biomicroscopically or by OCT
  • Ocular inflammation (including trace or above) in the study eye
  • Infectious blepharitis, keratitis, scleritis, or conjunctivitis (in either eye) or current treatment for serious systemic infection
  • Spherical equivalent of the refractive error in the study eye of more than -8 diopters myopia (For patients who have had refractive or cataract surgery in the study eye, pre-operative spherical equivalent refractive error of more than -8 diopters myopia is not allowed)
  • Systemic Conditions
  • Uncontrolled Blood pressure exceeding diastolic pressure of 100 mm Hg (sitting) during the screening period
  • Uncontrolled diabetes mellitus
  • Renal failure requiring dialysis or renal transplant
  • Pregnancy (positive pregnancy test) or lactation
  • Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD, or contraceptive hormone implant or patch.
  • Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated
  • Participation in another simultaneous medical investigation or trial
  • History of other disease, metabolic dysfunction, physical examination finding, or other findings giving reasonable suspicion of a disease or condition that contraindicates the use an investigational drug, might affect interpretation of the results of the study, or render the subject at high risk from treatment complications
  • Other
  • History of allergy to fluorescein, not amenable to treatment
  • Inability to obtain fundus photographs or fluorescein angiograms of sufficient quality to be analyzed and graded by the central reading center
  • Inability to comply with study or follow up procedures
  • History of allergy to humanized antibodies or any component of the ranibizumab formulation

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Retina Consultants of Houston

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase I Open Label Study of the Safety, Tolerability and Efficacy of 2.0 mg Ranibizumab in Subjects With Ischemic Central Retinal Vein Occlusion (RAVE2)

The RAVE 2 trial is a phase I, open label, 12-month trial of intravitreal ranibizumab 2.0 mg in patients with ischemic CRVO who have been either previously treated with ranibizumab or treatment naïve.

Read the detailed description

The most devastating complication of ischemic CRVO is the development of anterior segment neovascularization and the resulting morbidity from neovascular glaucoma. This complication appears to be directly correlated with intraocular VEGF levels. Currently there is no proven treatment to decrease the formation of rubeosis. Current management of the disease consists of pan-retinal photocoagulation once significant anterior segment neovascularization becomes manifest. This treatment destroys peripheral retina (with peripheral retinal field) and presumably works by eventually lowering ocular VEGF levels which causes secondary regression of rubeosis.

As ranibizumab blocks VEGF, this treatment when delivered intraocularly may prevent neo-vascular glaucoma while preserving peripheral visual fields in this patient population.

A higher dose of ranibizumab may allow for both a longer duration of treatment effect and potentially more efficacy leading to better outcomes for patients that are somewhat treatment resistant and need continual therapy. Nonclinical and early clinical data indicate that higher doses of ranibizumab up to and including 2.0 mg are safe and tolerated by patients.

Being tested
ranibizumab
Keywords
Ischemic, Central, Retinal, Vein, Occlusion, Ranibizumab, Lucentis, CRVO, ISCRVO
Medical subject headings
Ischemia, Retinal Vein Occlusion, Pathologic Processes, Retinal Diseases, Eye Diseases, Bites and Stings

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ranibizumabDrug

    Also called Lucentis

    Ranibizumab is formulated as a sterile solution aseptically filled in a sterile 3-mL stoppered glass vial. Each vial contains 0.5 mL of 40 mg/mL (2.0-mg dose level) ranibizumab aqueous solution.

Study groups in NCT01225146
Study groupRoleWhat they receive
Treatment Experienced (Cohort 1Active comparatorPreviously treated with 6 or more intravitreal ranibizumab with persistent edema followed in RAVE 1 (FVF3348s). Cohort 1 patients will receive 1 dose of ranibizumab 2.0 mg, followed by PRN based on pre-defined retreatment criteria
Receives: Drug: ranibizumab
Treatment Naive (Cohort 2)Active comparatorTreatment naïve. Cohort 2 patients will receive 6 doses of ranibizumab 2.0 mg, followed by PRN based on pre-defined re-treatment criteria.
Receives: Drug: ranibizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean Change in logMAR

    Mean change from baseline in ETDRS NCVA.

    Measured: 12 months.

Secondary outcomes (5)

  1. Incidence and Severity of Adverse Events (Ocular and Non-ocular).

    Incidence and severity of adverse events (ocular and non-ocular) from baseline through 12 months will be evaluated.

    Measured: 12 months

  2. Neovascularization Development

    Percent of patients that develop neovascularization of the iris, optic nerve and/or elsewhere.

    Measured: 12 months

  3. Mean Change in Central Foveal Volume

    Mean change in Central Foveal Volume on High Resolution OCT

    Measured: 12 months

  4. Changes, by Disc Areas, of Capillary Non-perfusion in the Periphery

    Changes, by disc areas, of capillary non-perfusion in the periphery (evaluated by wide-field fluorescein angiography) at 3, 6, 9 and 12 months from baseline.

    Measured: 12 months

  5. Goldman Visual Field Changes

    Goldman Visual Field changes at 6 and 12 months from baseline

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Oct 2010 (estimated)
  2. Study startOct 2010
  3. Primary completionAug 2012
  4. Study completionAug 2012

Why it stopped: The collaborator, Genentech, stopped supplying the study drug to the site.

Resources

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
Parallel groups
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01225146
Sponsor's protocol ID
FVF4820s
Acronym
RAVE2
Status last verified
May 2017
First submitted
14 Oct 2010
Last updated
14 Aug 2017
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Wykoff CC, Brown DM, Croft DE, Major JC Jr, Wong TP. Progressive retinal nonperfusion in ischemic central retinal vein occlusion. Retina. 2015 Jan;35(1):43-7. doi: 10.1097/IAE.0000000000000277.

    PubMed 25102193

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ranibizumab in people with Ischemia and Retinal Vein Occlusion, run by David M. Brown, M.D. at 1 site in United States.

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 13 inclusion and 37 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: stopped early, as of the sponsor's last update on 14 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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 14 Aug 2017). 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?

Mean Change in logMAR (time frame: 12 months.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01225146, which also lists 1 linked publication.

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 14 Aug 2017.

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