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

Diabetic Macular Edema Clinical Trial

— REEF  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01292798
• Other study ID #: FVF4978s
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: February 7, 2011
• Last updated: December 10, 2013
• Start date: March 2011
• Est. completion date: April 2013

Study information

• Verified date: December 2013
• Source: California Retina Consultants
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetic Macular Edema
• Edema
• Macular Edema

Intervention

Drug:
• Ranibizumab
0.05ml of 0.5mg or 2.0mg ranibizumab injected intravitreally

Locations

Country	Name	City	State
United States	California Retina Consultants	Bakersfield	California
United States	Retina Institute of Hawai'i	Honolulu	Hawaii
United States	California Retina Consultants	Oxnard	California
United States	California Retina Consultants	Santa Barbara	California
United States	California Retina Consultants	Santa Maria	California

Sponsors (2)

Lead Sponsor	Collaborator
California Retina Consultants	Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Visual Acuity Scores at Month 12 Compared to Baseline	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.	12 months	No
Secondary	Change in Central Retinal Thickness as Measured by OCT at Month 12 Compared to Baseline	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.	12 months	No
Secondary	Qualitative Assessment of Diabetic Macular Edema	To compare the percentage of subjects with complete resolution of diabetic macular edema between each subgroup, a) Partial-responders and b) Non-responders.	12 months	No
Secondary	Number of participants with ocular and systemic adverse events as a measure of safety and tolerability.	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.	12 months	Yes
Secondary	Participant Scores on Work Productivity and Activity Impairment Questionnaire	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.	Baseline, Month 3 and Month 12	No