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Macular EdemaPhase 4NCT01277302

A Study Evaluating Dosing Regimens for Treatment With Intravitreal Ranibizumab Injections in Subjects With Macular Edema Following Retinal Vein Occlusion

A Phase 4 study testing Ranibizumab in people with Macular Edema, run by Genentech, Inc. at 42 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This was a Phase IV multicenter, randomized, open-label study, with masking of the vision examiner, of the efficacy and safety of intravitreal ranibizumab 0.5 mg in subjects with macular edema following Branch Retinal Vein Occlusion (BRVO) or Central Retinal Vein Occlusion (CRVO). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Macular Edema
What is being tested?
Ranibizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
202 participants
Where
42 sitesUnited States
Study dates
Feb 2011to Oct 2012
Phase
Phase 4
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
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • For sexually active women of childbearing potential, use of an appropriate form of contraception (or abstinence) for the duration of the study.
  • Ocular Inclusion Criteria (Study Eye)
  • Foveal center-involved macular edema secondary to branch retinal vein occlusion (BRVO) (including hemi-retinal retinal vein occlusion [HRVO]) or central retinal vein occlusion (CRVO).
  • Best corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study (ETDRS) charts of 20/40 to 20/320 (Snellen equivalent) in the study eye.
  • Mean central subfield thickness > 300 µm on 2 spectral-domain optical coherence tomography measurements (screening and Day 0 [first day of treatment]).

Who cannot join

  • History of cerebral vascular accident or myocardial infarction within 3 months prior to Day 0.
  • History of any systemic anti-vascular endothelial growth factor (VEGF) or pro-VEGF treatment within 6 months prior to Day 0.
  • History of allergy to fluorescein.
  • History of allergy to ranibizumab injection or related molecule.
  • Relevant systemic disease that may be associated with increased systemic VEGF levels. History of successfully treated malignancies is not an exclusion criterion.
  • Uncontrolled blood pressure.
Show all 38Show fewer
  • Pregnancy or lactation.
  • Daily use of oral corticosteroids to treat a chronic condition.
  • Required treatment with injectable corticosteroids to treat a musculoskeletal condition.
  • Participation in an investigational trial within 30 days prior to Day 0 that involved treatment with any drug or device that has not received regulatory approval at the time of study entry.
  • Ocular Exclusion Criteria (Study Eye)
  • Prior episode of retinal vein occlusion (RVO).
  • Brisk afferent pupillary defect.
  • History of any previous intravitreal anti-VEGF therapy for RVO in the study eye.
  • History of previous therapeutic treatment for RVO, other than anti-VEGF therapy, within 4 months prior to the screening visit, including any intraocular corticosteroids.
  • History of previous surgical treatment for RVO, including radial optic neurotomy or sheathotomy.
  • History or presence of age-related macular degeneration (AMD) (dry form graded as Age-Related Eye Disease Study [AREDS] Stage 2 or higher or wet form).
  • History of laser photocoagulation for macular edema within 4 months prior to Day 0.
  • History of panretinal scatter photocoagulation or sector laser photocoagulation within 4 months prior to Day 0 or anticipated within the next 4 months following Day 0.
  • History of pars plana vitrectomy.
  • History of intraocular surgery within 2 months prior to Day 0 or anticipated within the next 7 months following Day 0.
  • History of yttrium-aluminum-garnet (YAG) capsulotomy performed within 2 months prior to Day 0.
  • Previous filtration surgery in the study eye.
  • History of herpetic ocular infection.
  • History of ocular toxoplasmosis.
  • History of rhegmatogenous retinal detachment.
  • History of idiopathic central serous chorioretinopathy.
  • Evidence upon examination of vitreoretinal interface disease either on clinical examination or spectral-domain optical coherence tomography (SD-OCT), thought to be contributing to macular edema.
  • Presence of an ocular condition that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the study.
  • Visually significant hemorrhage obscuring the fovea and felt to be a major contributor to reduced visual acuity. The subject should be followed and when the hemorrhage in the fovea clears to the point that it is no longer a major contributor to reduced visual acuity, the subject may be screened for the study.
  • Presence of a substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more.
  • Intra-ocular pressure (IOP) ≥ 30 mmHg. If a subject's IOP is ≥ 30 mmHg, that subject will be referred for glaucoma treatment and may be re-screened after 1 month.
  • Evidence upon examination of pseudoexfoliation.
  • Aphakia.
  • Evidence upon examination of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis.
  • Evidence upon examination of any diabetic retinopathy, defined as eyes of diabetic patients with more than one microaneurysm outside the area of the vein occlusion (inclusive of both eyes).
  • Other relevant ocular disease that may be associated with increased intraocular VEGF levels.
  • Improvement of ≥ 10 letters on best-corrected visual acuity ETDRS score between screening and Day 0.

Trial locations and contacts

42 sites in 1 country.

42 sites in 1 country

United States42 sites

  • Study site

    Abilene, Texas, 79606

  • Study site

    Altamonte Springs, Florida, 32701

  • Study site

    Augusta, Georgia, 30909

  • Study site

    Austin, Texas, 78705

  • Study site

    Baltimore, Maryland, 21287

  • Study site

    Beverly Hills, California, 90211

  • Study site

    Boston, Massachusetts, 02114

  • Study site

    Boynton Beach, Florida, 33426

  • Study site

    Camp Hill, Pennsylvania, 17011

  • Study site

    Charlotte, North Carolina, 28210

  • Study site

    Chicago, Illinois, 60637

  • Study site

    Chico, California, 95973

  • Study site

    Colorado Springs, Colorado, 80909

  • Study site

    Edina, Minnesota, 55435

  • Study site

    Golden, Colorado, 80401

  • Study site

    Hagerstown, Maryland, 21740

  • Study site

    Houston, Texas, 77030

  • Study site

    Jackson, Michigan, 49201

  • Study site

    Ladson, South Carolina, 29456

  • Study site

    Lakeland, Florida, 33805

  • Study site

    Las Vegas, Nevada, 89144

  • Study site

    Mountain View, California, 94040

  • Study site

    Nashville, Tennessee, 37203

  • Study site

    New London, Connecticut, 06320

  • Study site

    Northfield, New Jersey, 08225

  • Study site

    Oakland, California, 94609

  • Study site

    Philadelphia, Pennsylvania, 19107

  • Study site

    Phoenix, Arizona, 85020

  • Study site

    Pittsburgh, Pennsylvania, 15212

  • Study site

    Pittsburgh, Pennsylvania, 15213

  • Study site

    Rapid City, South Dakota, 57701

  • Study site

    Rochester, New York, 14620

  • Study site

    San Antonio, Texas, 78240

  • Study site

    San Francisco, California, 94107

  • Study site

    Santa Ana, California, 92705

  • Study site

    Santa Barbara, California, 93103

  • Study site

    Teaneck, New Jersey, 07666

  • Study site

    The Woodlands, Texas, 77384

  • Study site

    Torrance, California, 90503

  • Study site

    Tucson, Arizona, 85704

  • Study site

    West Columbia, South Carolina, 29169

  • Study site

    Worcester, Massachusetts, 01605

Other trials in United States

About this study

Official title: A Multicenter Randomized Study Evaluating Dosing Regimens for Treatment With Intravitreal Ranibizumab Injections in Subjects With Macular Edema Following Retinal Vein Occlusion

This was a Phase IV multicenter, randomized, open-label study, with masking of the vision examiner, of the efficacy and safety of intravitreal ranibizumab 0.5 mg in subjects with macular edema following Branch Retinal Vein Occlusion (BRVO) or Central Retinal Vein Occlusion (CRVO).

Read the detailed description

This study consisted of 2 study periods, a 7-month fixed treatment period, followed by an 8-month alternate dose regimen period. Subjects could receive up to a maximum of 15 monthly injections of ranibizumab 0.5 mg during the study, 7 injections (Day 0 and at 6 monthly visits) in the fixed treatment period and a maximum of 8 injections in the alternate dose regimen period. During the fixed treatment period, subjects received 7 monthly intravitreal ranibizumab 0.5 mg injections. During the alternate dose regimen period, from Month 7 through Month 14, subjects were evaluated monthly to determine whether they achieved the study-specific visual acuity and spectral-domain optical coherence tomography (VA-OCT) stability criteria. Subjects continued to receive monthly ranibizumab 0.5 mg monthly injections until the VA-OCT stability criteria were first met. Upon meeting the VA-OCT stability criteria for the first time during the alternate dose regimen period, subjects were randomly assigned in a 1:1 ratio to one of 2 dose regimens, the PRN (pro re nata, "as-needed") or the Monthly regimen.

PRN randomized subjects: Subjects received no injection at the randomization visit and at future monthly visits where the VA-OCT stability criteria were met and received a ranibizumab 0.5 mg injection at future monthly visits if the VA-OCT stability criteria were not met.

Monthly randomized subjects: Subjects continued to receive ranibizumab 0.5 mg injections at each monthly visit.

Monthly non-randomized subjects: Subjects who did not meet the VA-OCT stability criteria at any month from Month 7 through Month 14 were not randomized and received 8 monthly intravitreal ranibizumab 0.5 mg injections.

Conditions
Macular Edema
Being tested
Ranibizumab
Medical subject headings
Macular Edema

What participants receive

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

  • RanibizumabDrug

    Also called Lucentis

    Liquid ranibizumab (10 mg/ml) was supplied in a sterile solution in single-use vials.

Study groups in NCT01277302
Study groupRoleWhat they receive
Ranibizumab 0.5 mg monthly - randomized subjectsExperimentalSubjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific visual acuity and spectral-domain optical coherence tomography (VA-OCT) stability criteria were met and randomization occurred to the monthly arm. At subsequent monthly visits after randomization, injections were given whether the VA-OCT stability criteria were met or not met. Subjects were to receive 15 ranibizumab 0.5 mg injections.
Receives: Drug: Ranibizumab
Ranibizumab 0.5 mg PRN - randomized subjectsExperimentalSubjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections until the first month where the study-specific VA-OCT stability criteria were met and randomization occurred to the PRN arm. No injection was given at the randomization visit. At subsequent monthly visits after randomization, injections were given if the VA-OCT stability criteria were not met and no injections were given if the VA-OCT stability criteria were met. Subjects could receive between 7 and a maximum of 14 ranibizumab 0.5 mg injections.
Receives: Drug: Ranibizumab
Ranibizumab 0.5 mg monthly - non-randomized subjectsExperimentalSubjects received at least 7 monthly intravitreal ranibizumab 0.5 mg injections and then never met the study-specific VA-OCT stability criteria from month 7 to month 14. Subjects were to receive 15 ranibizumab 0.5 mg injections.
Receives: Drug: Ranibizumab

What is being measured

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

  1. Trend of Change From Baseline in the Best Corrected Visual Acuity (BCVA) Scores From Month 7 to Month 15

    BCVA was measured in the study eye using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. An increase in the BCVA score indicates an improvement of vision. A positive change score indicates improvement. The reported data are the observed changes from Baseline in BCVA at Months 7 and 15. For the statistical analysis, the interaction term of treatment by time in a longitudinal model was used to assess whether there was a difference in the trend of change from Baseline in the visual acuity scores from Month 7 to Month 15 between the 2 randomized treatment groups, Monthly and PRN.

    Measured: Baseline to Month 15

Secondary outcomes (8)

  1. Visual Acuity Change From Previous Month During the Alternate Dose Regimen Period in Subjects Who Met the VA-OCT Stability Criteria at the Previous Month

    BCVA was measured in the study eye using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. An increase in the BCVA score indicates an improvement of vision. A positive change score indicates improvement. This outcome measure is not relevant for subjects in the non-randomized group because they never met the VA-OCT stability criteria.

    Measured: Month 7 through Month 15

  2. Percentage of Participants Who Gained ≥ 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline

    BCVA was measured in the study eye using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. An increase in the BCVA score indicates an improvement of vision.

    Measured: Month 7 to Month 15

  3. Percentage of Participants With a Visual Acuity (VA) Snellen Equivalent of 20/40 or Better

    VA was measured in the study eye using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart starting at a test distance of 4 meters. An increase in the number of lines read correctly by the patient in the ETDRS chart indicates an improvement of vision. The Snellen equivalent of 20/40 or better is 69 or more letters correctly read in the EDTRS chart.

    Measured: Month 7 to Month 15

  4. Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score

    BCVA was measured in the study eye using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. An increase in the BCVA score indicates an improvement of vision. A positive change score indicates improvement.

    Measured: Month 1 to Month 15

  5. Percentage of Participants Who Lost < 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline

    BCVA was measured in the study eye using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient. An increase in the BCVA score indicates an improvement of vision.

    Measured: Month 7 to Month 15

  6. Percentage of Participants With a Central Foveal Thickness of ≤ 300 µm

    Central foveal thickness was assessed monthly in the study eye using spectral-domain optical coherence tomography. Central foveal thickness was computed using the automated Cirrus Review software (DOCTR CZM Cirrus OCT Grader Reading Manual, Version 1.02). All participants in the Monthly and PRN groups had a baseline central foveal thickness > 300 µm at baseline.

    Measured: Month 7 to Month 15

  7. Mean Change From Baseline in Central Foveal Thickness

    Central foveal thickness was assessed monthly in the study eye using spectral-domain optical coherence tomography. Central foveal thickness was computed using the automated Cirrus Review software (DOCTR CZM Cirrus OCT Grader Reading Manual, Version 1.02). All participants in the Monthly and PRN groups had a baseline central foveal thickness > 300 µm at baseline. A decrease in foveal thickness suggests a reduction in macular edema. A negative change score indicates improvement.

    Measured: Month 1 to Month 15

  8. Percentage of Participants With Intraretinal Edema

    The presence of intraretinal edema was defined as the presence of subretinal fluid, cystoid spaces, or central retinal thickness ≥ 300 µm as evaluated in spectral-domain optical coherence tomography images by the Digital Angiography Reading Center, the central reading center. At baseline, all participants in the Monthly and PRN groups had presence of edema.

    Measured: Month 7 to Month 15

Timeline

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

  1. First posted14 Jan 2011 (estimated)
  2. Study startFeb 2011
  3. Primary completionOct 2012
  4. Study completionOct 2012

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 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
202 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01277302
Sponsor's protocol ID
FVF4967g
Other IDs
ML01296
Status last verified
Mar 2014
First submitted
13 Jan 2011
Last updated
23 Apr 2014

Publications

  • Yiu G, Huang D, Wang Y, Wang Z, Yang M, Haskova Z. Predictors of As-Needed Ranibizumab Injection Frequency in Patients With Macular Edema Following Retinal Vein Occlusion. Am J Ophthalmol. 2023 May;249:74-81. doi: 10.1016/j.ajo.2023.01.004. Epub 2023 Jan 14.

    PubMed 36646240

  • Lloyd Clark W, Liu M, Kitchens J, Wang PW, Haskova Z. Baseline characteristics associated with early visual acuity gains after ranibizumab treatment for retinal vein occlusion. BMC Ophthalmol. 2019 Jan 8;19(1):11. doi: 10.1186/s12886-018-1012-y.

    PubMed 30621653

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Ranibizumab in people with Macular Edema, run by Genentech, Inc. at 42 sites 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 5 inclusion and 38 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 23 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 42 sites 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 23 Apr 2014). 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?

Trend of Change From Baseline in the Best Corrected Visual Acuity (BCVA) Scores From Month 7 to Month 15 (time frame: Baseline to Month 15). 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 NCT01277302, which also lists 2 linked publications.

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 23 Apr 2014.

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