Ranibizumab 0.5mg and 2.0mg to Treat Diabetic Macular Edema in Patients With Poor Response to Bevacizumab (REEF)

March 23, 2016 updated by: California Retina Consultants

Open Label, Phase I/II, Residual Edema Evaluation With 0.5mg and 2.0mg Ranibizumab Formulations (REEF)

This is an open-label, Phase I/II study of intravitreally administered ranibizumab either 0.5-mg and/or 2.0-mg in subjects with clinical, angiographic, and ocular coherence tomography (OCT) evidence of diabetic retinopathy with associated diabetic macular edema following bevacizumab therapy. Thirty patients will be enrolled in this study.

Consented, enrolled subjects will receive multiple open-label intravitreal injections of 0.5 mg ranibizumab administered every 30 days (±7 days) for 3 injections during the mandatory treatment phase (Day 0, Month 1, and Month 2).

Subjects with complete resolution of diabetic macular edema after 3 intravitreal injections of 0.5 mg ranibizumab will be treated as necessary with 0.5 mg ranibizumab to treat recurrent macular edema for an additional 9 months (12 months from Day 0). The intent is to administer additional ranibizumab treatment if there is evidence of disease activity documented on OCT (e.g., intra-retinal fluid, subretinal fluid and/or cystic changes).

Subjects with residual diabetic macular edema following 3 intravitreal injections of 0.5 mg ranibizumab will be receive 3 intravitreal injections of 2.0 mg ranibizumab administered every 30 days (±7 days) for 3 injections at the Month 3, Month 4, and Month 5 study visits.

Beginning at the Month 6 study visit, subjects with complete resolution of diabetic macular edema following 3 intravitreal injections of 2.0 mg ranibizumab will treated as necessary with 2.0 mg ranibizumab injections only to treat recurrent macular edema for an additional 6 months (12 months from Day 0).

Subjects with residual diabetic macular edema following 3 consecutive intravitreal injections of 2.0 mg ranibizumab will be treated as necessary with 2.0 mg ranibizumab to treat persistent or recurrent macular edema for an additional 6 months (12 months from Day 0). Focal photocoagulation or intravitreal triamcinolone may be administered at the physician's discretion as an adjunct to ranibizumab injections beginning at Month 6 through Month 12 of the study.

All subjects will make monthly visits for 12 months for evaluation of safety and efficacy. All subjects will have their first injection of ranibizumab on Day 0 and undergo a safety visit one week (±2 days) after the first injection. At subsequent visits, the subject will have a safety evaluation at the monthly scheduled follow-up visit prior to any intravitreal injection. Subjects will be contacted by the site personnel 1-2 days after each injection to elicit reports of decreased vision or pain or unusual new ocular symptoms in the study eye.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
43

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Bakersfield, California, United States, 93309
        • California Retina Consultants
      • Oxnard, California, United States, 93030
        • California Retina Consultants
      • Santa Barbara, California, United States, 93103
        • California Retina Consultants
      • Santa Maria, California, United States, 93454
        • California Retina Consultants
    • Hawaii
      • Honolulu, Hawaii, United States, 69815
        • Retina Institute of Hawai'i

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Ability to provide written informed consent and comply with study assessments for the full duration of the study
  • Age > 18 years
  • Diagnosis of diabetes mellitus (type 1 or 2)Any one of the following will be considered to be sufficient evidence that diabetes is present:Current regular use of insulin for treatment of diabetes or current regular use of oral anti-hyperglycemia agent for the treatment of diabetes
  • Clinical evidence of retinal thickening due to macular edema involving the center of the macula, associated with diabetic retinopathy.
  • Previous history of two consecutive intravitreal bevacizumab injections for the treatment of diabetic macular edema with documented incomplete resolution of central subfield thickening by OCT (consecutive injections administered < 7 weeks apart and within the past 12 months).
  • Central diabetic macular edema present on clinical examination and OCT testing with central 1mm subfield thickness greater than 300 microns as measured on SD-OCT.
  • Visual acuity score greater than or equal to 19 letters (20/400) and less than or equal to 73 letters (20/40) by the ETDRS visual acuity protocol.
  • Media clarity, pupillary dilation and patient cooperation sufficient to allow OCT testing and retinal photography

Exclusion Criteria:

  • Pregnancy (positive pregnancy test) or known to be pregnant; also pre-menopausal women not using adequate contraception.
  • Participation in another ocular investigation or trial simultaneously
  • Blood pressure > 180/110 (systolic above 180 OR diastolic above 110)
  • Any condition that, in the opinion of the investigator, would preclude participation in the study (e.g. chronic alcoholism, drug abuse)
  • Evidence of vitreoretinal interface abnormality after ocular exam or OCT that may be contributing to the macular edema
  • An eye that, in the investigator's opinion, has no chance of improving in visual acuity following resolution of macular edema (e.g. presence of subretinal fibrosis or geographic atrophy)
  • Presence of another ocular condition that may affect the visual acuity or macular edema during the course of the study (e.g. AMD, uveitis, Irvine-Gas)
  • Evidence of neovascularization of the iris or retina
  • Evidence of central atrophy or fibrosis in the study eye
  • Presence of substantial cataract, one that might decrease the vision by 3 or more lines of vision at sometime during the study.
  • History of vitreous surgery in the study eye
  • History of cataract surgery within 6 months of enrollment.
  • History of YAG capsulotomy within 2 months of enrollment.
  • Visual acuity <20/400 in the fellow eye
  • Uncontrolled glaucoma (pressure >30) despite treatment with glaucoma medications.
  • History of cerebral vascular accident or myocardial infarction within 3 months prior to Day 0.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 0.5mg and 2.0mgRanibizumab
Three consecutive intravitreal ranibizumab 0.5mg injections followed by three consecutive intravitreal ranibizumab 2.0mg injections if specific criteria is met.
Drug: Ranibizumab
0.05ml of 0.5mg or 2.0mg ranibizumab injected intravitreally
Other Names:
  • Lucentis

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall Mean Change in Visual Acuity Scores at Month 6 Compared to Baseline
Time Frame: baseline and 6 months
To determine the mean change in the best-corrected visual acuity on an ETDRS visual acuity chart at a starting distance of 4 meters from baseline to 6 months.
baseline and 6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mean Change in 1-mm Central Subfield (CST) Thickness as Measured by OCT at Month 6 Compared to Baseline
Time Frame: baseline and 6 months
To determine the mean change in central 1-mm subfield thickness as measured by spectral-domain OCT from baseline to 6 months .
baseline and 6 months
Qualitative Assessment of Diabetic Macular Edema (DME)
Time Frame: Baeline and 6 months
To compare the percentage of subjects with compete or partial/no resolution of diabetic macular edema in response to the ranibizumab 0.5 and 2.0 mg doses.
Baeline and 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
California Retina Consultants

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Genentech, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Dante Pieramici, MD, California Retina Consultants

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 7, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 9, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 10, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 22, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 23, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • FVF4978s

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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