The Ranibizumab for Edema of the mAcula in Diabetes-2 (READ-2) Study

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00407381
• Collaborator: Juvenile Diabetes Research Foundation (Other), Genentech, Inc. (Industry)
• Enrollment: 126
• Locations: 20
• Arms: 3
• Duration (Months): 56
• Patients Per Site: 6.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study is being done to see if the investigational drug Ranibizumab (RBZ) given by injection into the eye, is safe and effective to use in people with diabetic macular edema (DME). The investigators want to compare RBZ to laser treatment which is the current standard way to treat DME.

RBZ blocks a growth factor that is thought to be involved in the formation of abnormal blood vessels that cause loss of vision in patients with DME.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Macular Edema	Drug: Ranibizumab; Procedure: Laser photocoagulation	Phase 2

Detailed Description

The READ-2 Study is a phase 2 randomized, multi-center clinical trial to be conducted under an investigator-initiated investigational new drug (IND). The study aims to enroll 126 patients, who will be randomized into 3 different groups. The primary objectives of the READ-2 Study are: (a) to obtain data on the bioactivity and dose interval effects of intravitreal ranibizumab (RBZ) alone, as well as in combination with laser photocoagulation, on retinal thickness and visual acuity in subjects with DME; and (b) to obtain additional safety and bioactivity data to aid in the design of a phase 3 clinical trial to evaluate ranibizumab as a therapeutic option for patients with DME The study consists of a 2-week screening period (Days -14 to 0), a 6-month treatment period with a primary time endpoint, and a 18-month follow-up and treatment period with secondary time endpoints. Consented subjects will enter the 14-day screening period to determine eligibility. Serum chemistry and hematology testing, urinalysis, pregnancy testing, and macular thickness measurements based on optical coherence tomography (OCT) will be performed. Screening will also include VA, ophthalmic examination and fluorescein angiography (FA) entry criteria.

Patients who have ETDRS visual acuity of 20/40 or worse, but better than or equal to 20/320 due to foveal thickening from macular edema secondary to diabetes (type 1 or 2) and who meet eligibility criteria will be eligible to enroll in the study. Baseline foveal thickness by OCT must be at least 250, which is often associated with VA of 20/40 or worse and which provides sufficient thickening so that a treatment effect is easily detectable (Nguyen et al. 2004). Approximately 126 patients with DME will be enrolled in this study from all clinical sites in the study. Every effort will be made to recruit and enroll eligible patients from men and women of all ethnic and social backgrounds. Patients who meet entry criteria will be able to enroll in the study until the quota of patients has been achieved.

Study Design

• Study Type: Interventional
• Actual Enrollment: 126 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Ranibizumab for Edema of the Macula in Diabetes: a Phase 2 Study ( The Read-2 Study)
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Aug 1, 2010
• Actual Study Completion Date: Aug 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ranibizumab Ranibizumab (RBZ) intravitreal injection alone	Drug: Ranibizumab; Ranibizumab for intravitreal injection. .05ml dosing at 30 day intervals and pro re nata (PRN) with dosing criteria.; Other Names: Lucentis
Active Comparator: Laser Laser photocoagulation	Procedure: Laser photocoagulation; Laser photocoagulation in either focal or grid pattern as determined by investigator.
Experimental: Laser with Ranibizumab Laser following intravitreal injection of RBZ	Drug: Ranibizumab; Ranibizumab for intravitreal injection. .05ml dosing at 30 day intervals and pro re nata (PRN) with dosing criteria.; Other Names: Lucentis ; Procedure: Laser photocoagulation; Laser photocoagulation in either focal or grid pattern as determined by investigator.

Outcome Measures

Primary Outcome Measures

1. Mean Change in Best Corrected Visual Acuity (BCVA) at Month 6 [6 months]

   Mean change of best corrected visual acuity letters (BCVA) at month 6

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion:

• Signed informed consent and authorization of use and disclosure of protected health information

• Age greater than 18 years

• Diagnosis of diabetes mellitus (type 1 or type 2) and serum HbA1c greater than 5.5% within 12 months of randomization

• Retinal thickening secondary to diabetes mellitus (diabetic macular edema) involving the center of the fovea.

• Diagnosis must be confirmed by OCT images

• Foveal thickness of greater than 250, as assessed by OCT

• Best corrected visual acuity score in the study eye of 20/40 to 20/320 inclusive (Snellen equivalents using the ETDRS protocol at a distance of 4 meters). Only one eye will be treated in the study. If both eyes are eligible, the investigator will select the eye to be enrolled. Visual acuity in the non-study eye must be greater than 20/800.

• In the opinion of the investigator, decreased vision in the study eye is due to foveal thickening from DME and not from other obvious causes.

• In the opinion of the investigator, laser photocoagulation can be withheld for at least 30 days after the patient has enrolled in the study

Exclusion Criteria:

• Panretinal photocoagulation or macular photocoagulation within 3 months of study entry in the study eye

• Use of intraocular or periocular injection of steroids in the study eye (e.g., triamcinolone) within 3 months of study entry

• Previous participation in a study and receipt of anti-angiogenic drugs (pegaptanib sodium, ranibizumab, anecortave acetate, protein kinase C inhibitor, etc.) within 2 months of study entry

• Eyes in which the investigators do not feel appropriate to do any additional laser photocoagulation

• Proliferative diabetic retinopathy in the study eye, with the exceptions of inactive, fibrotic proliferative diabetic retinopathy that has regressed following pan-retinal laser photocoagulation or tufts of neovascularization elsewhere (NVE) less than one disc area with no vitreous hemorrhage

• Vitreomacular traction or epiretinal membrane in the study eye evident biomicroscopically or by OCT

• Structural damage to the center of the macula in the study eye 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), macular ischemia, or organized hard exudate plaque

• Ocular disorders in the study eye that may confound interpretation of study results, including retinal vascular occlusion, retinal detachment, macular hole, or choroidal neovascularization of any cause (e.g., age related macular degeneration (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 first 6-month study period

• Eyes which are likely to need cataract surgery and intraocular lens implantation within the first 6 months of the study

• Cataract surgery in the study eye within 3 months of study entry; Yttrium-Aluminum-Garnet (YAG) laser capsulotomy within 2 months of study entry; or any other intraocular surgery within 3 months preceding Day 0.

• History of vitreoretinal surgery in the study eye within 3 months of study entry

• Uncontrolled glaucoma (defined as intraocular pressure greater than 30 mm Hg despite treatment with anti-glaucoma medications)

• Uncontrolled diabetes mellitus, as evidenced by glycosylated hemoglobin (HbA1c) value greater than 12%

• Premenopausal women not using adequate contraception

• Any women who are pregnant

• International normalized ratio (INR) greater than or equal to 3.0 (e.g. due to current treatment with warfarin). The use of aspirin or other anticoagulants is not an exclusion

• History of gastrointestinal bleeding within 2 months of study enrollment

• History of major gastrointestinal, cardiothoracic, gynecological, genitourinary, or orthopedic surgeries within 2 months of study enrollment

• History of cerebral vascular accident, myocardial infarction, transient ischemic attacks within 6 months of study enrollment

• Any patients who are on renal dialysis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Retinal Consultants of Arizona	Phoenix	Arizona	United States	85014
2	Retina-Vitreous Associates Medical Group	Beverly Hills	California	United States	90211
3	University of Southern California	Los Angeles	California	United States	90033
4	East Bay Retina Consultants	Oakland	California	United States	94609
5	Retina Institute of California	Pasadena	California	United States	91105
6	University of California, San Francisco	San Francisco	California	United States	94143
7	Yale Eye Center	New Haven	Connecticut	United States	06511
8	Emory University	Atlanta	Georgia	United States	30322
9	Illinois Retina Associates Rush University	Chicago	Illinois	United States	60435
10	University of Chicago	Chicago	Illinois	United States	60637
11	Midwest Eye Institute	Indianapolis	Indiana	United States	46280
12	Wilmer Eye Institute at Johns Hopkins University School of Medicine	Baltimore	Maryland	United States	21287
13	Ophthalmic Consultants of Boston	Boston	Massachusetts	United States	02114
14	New England Retina Consultants, PC	West Springfield	Massachusetts	United States	01089
15	Retinal Consultants of Nevada	Las Vegas	Nevada	United States	89109
16	University of New Mexico	Albuquerque	New Mexico	United States	87131
17	Duke Eye Center	Durham	North Carolina	United States	27710
18	Eye Care Specialists, PC	Kingston	Pennsylvania	United States	18704
19	Southern New England Retina Associates	Providence	Rhode Island	United States	02903
20	Black Hills Regional Eye Institute	Rapid City	South Dakota	United States	57701

Sponsors and Collaborators

• Johns Hopkins University
• Juvenile Diabetes Research Foundation
• Genentech, Inc.

Investigators

• Principal Investigator: Diana Do, MD, Truhlsen Eye Institute, University of Nebraska Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT00407381
• Other Study ID Numbers: NA_00005254
• First Posted: Dec 5, 2006
• Last Update Posted: Mar 31, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by Johns Hopkins University: DME
• Additional relevant MeSH terms: Macular Edema; Edema; Ranibizumab

Study Results

Participant Flow

Arm/Group Title	Ranibizumab Only	Laser Only	Laser With Ranibizumab (RBZ)
Arm/Group Description	Ranibizumab (RBZ) intravitreal injection alone Ranibizumab: Ranibizumab for intravitreal injection. .05ml dosing at 30 day intervals and pro re nata (PRN) with dosing criteria.	Laser photocoagulation Laser photocoagulation: Laser photocoagulation in either focal or grid pattern as determined by investigator.	Laser following intravitreal injection of RBZ Ranibizumab: Ranibizumab for intravitreal injection. .05ml dosing at 30 day intervals and PRN with dosing criteria. Laser photocoagulation: Laser photocoagulation in either focal or grid pattern as determined by investigator.
Period Title: Overall Study
STARTED	42	42	42
COMPLETED	39	38	40
NOT COMPLETED	3	4	2

Baseline Characteristics

Arm/Group Title	Ranibizumab Only	Laser Only	Laser With RBZ	Total
Arm/Group Description	RBZ intravitreal injection alone Ranibizumab: Ranibizumab for intravitreal injection. .05ml dosing at 30 day intervals and PRN with dosing criteria.	Laser photocoagulation Laser photocoagulation: Laser photocoagulation in either focal or grid pattern as determined by investigator.	Laser following intravitreal injection of RBZ Ranibizumab: Ranibizumab for intravitreal injection. .05ml dosing at 30 day intervals and PRN with dosing criteria. Laser photocoagulation: Laser photocoagulation in either focal or grid pattern as determined by investigator.	Total of all reporting groups
Overall Participants	42	42	42	126
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	62	62	62	62
Sex: Female, Male (Count of Participants)
Female	29 69%	23 54.8%	22 52.4%	74 58.7%
Male	13 31%	19 45.2%	20 47.6%	52 41.3%

Outcome Measures

1. Primary Outcome

Title	Mean Change in Best Corrected Visual Acuity (BCVA) at Month 6
Description	Mean change of best corrected visual acuity letters (BCVA) at month 6
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Mean change in BCVA at month 6

Arm/Group Title	RBZ Alone	Laser Alone	Laser With RBZ
Arm/Group Description	RBZ intravitreal injection alone Ranibizumab: Ranibizumab for intravitreal injection. .05ml dosing at 30 day intervals and PRN with dosing criteria.	Laser photocoagulation Laser photocoagulation: Laser photocoagulation in either focal or grid pattern as determined by investigator.	Laser following intravitreal injection of RBZ Ranibizumab: Ranibizumab for intravitreal injection. .05ml dosing at 30 day intervals and PRN with dosing criteria. Laser photocoagulation: Laser photocoagulation in either focal or grid pattern as determined by investigator.
Measure Participants	42	42	42
Mean (Standard Deviation) [Mean letter change in BCVA]	7.24 (5.54)	-0.43 (4.56)	3.8 (5.2)

Adverse Events

Time Frame	6 Months
Arm/Group Title	Ranibizumab Only		Laser Only		Laser With Ranibizumab
Arm/Group Description	RBZ intravitreal injection alone Ranibizumab: Ranibizumab for intravitreal injection. .05ml dosing at 30 day intervals and PRN with dosing criteria.		Laser photocoagulation Laser photocoagulation: Laser photocoagulation in either focal or grid pattern as determined by investigator.		Laser following intravitreal injection of RBZ Ranibizumab: Ranibizumab for intravitreal injection. .05ml dosing at 30 day intervals and PRN with dosing criteria. Laser photocoagulation: Laser photocoagulation in either focal or grid pattern as determined by investigator.
All Cause Mortality
	Ranibizumab Only		Laser Only		Laser With Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Ranibizumab Only		Laser Only		Laser With Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/42 (0%)		1/42 (2.4%)
Vascular disorders
Cerebrovascular Event	0/42 (0%)	0	0/42 (0%)	0	1/42 (2.4%)	1
Other (Not Including Serious) Adverse Events
	Ranibizumab Only		Laser Only		Laser With Ranibizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/42 (2.4%)		4/42 (9.5%)		3/42 (7.1%)
Eye disorders
Vitreous Hemorrhages	1/42 (2.4%)	1	4/42 (9.5%)	4	3/42 (7.1%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.