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

This study has been completed.
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
California Retina Consultants
ClinicalTrials.gov Identifier:
NCT01292798
First received: February 7, 2011
Last updated: December 10, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Diabetic Macular Edema
Drug: Ranibizumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open Label, Phase I/II, Residual Edema Evaluation With 0.5mg and 2.0mg Ranibizumab Formulations (REEF)

Resource links provided by NLM:


Further study details as provided by California Retina Consultants:

Primary Outcome Measures:
  • Change in Visual Acuity Scores at Month 12 Compared to Baseline [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To determine the mean change from baseline in best-corrected visual acuity in each subgroup, a) Partial-responders and b) Non-responders, on ETDRS visual acuity chart at a starting distance of 4 meters at 12 months.


Secondary Outcome Measures:
  • Change in Central Retinal Thickness as Measured by OCT at Month 12 Compared to Baseline [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To determine the mean change from baseline in center point thickness, central 1mm subfield thickness and total macular volume as measured by spectral-domain OCT.

  • Qualitative Assessment of Diabetic Macular Edema [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    To compare the percentage of subjects with complete resolution of diabetic macular edema between each subgroup, a) Partial-responders and b) Non-responders.

  • Number of participants with ocular and systemic adverse events as a measure of safety and tolerability. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    The safety of ranibizumab will be assessed through the collection and analysis of adverse events (AEs), baseline medical conditions, and complete ocular examination. All safety assessments, including the occurrence of AEs, intensity, relationship to study drug, and treatment or action taken to resolve the event, will be performed by an investigating physician.

  • Participant Scores on Work Productivity and Activity Impairment Questionnaire [ Time Frame: Baseline, Month 3 and Month 12 ] [ Designated as safety issue: No ]
    Each participant will be asked to complete a short questionnaire in order to assess the effect of diabetes eye related problems on a participant's ability to work and perform regular daily activities.


Enrollment: 40
Study Start Date: March 2011
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Lucentis

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01292798

Locations
United States, California
California Retina Consultants
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
United States, Hawaii
Retina Institute of Hawai'i
Honolulu, Hawaii, United States, 69815
Sponsors and Collaborators
California Retina Consultants
Genentech, Inc.
Investigators
Principal Investigator: Dante Pieramici, MD California Retina Consultants
  More Information

No publications provided

Responsible Party: California Retina Consultants
ClinicalTrials.gov Identifier: NCT01292798     History of Changes
Other Study ID Numbers: FVF4978s
Study First Received: February 7, 2011
Last Updated: December 10, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by California Retina Consultants:
Diabetes
Macula
Edema
Retina

Additional relevant MeSH terms:
Edema
Macular Edema
Eye Diseases
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on October 21, 2014