Ranibizumab for Edema of the Macula in Diabetes: Protocol 3 With High Dose - the READ 3 Study

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01077401
• Collaborator: Juvenile Diabetes Research Foundation (Other)
• Enrollment: 152
• Locations: 13
• Arms: 2
• Duration (Months): 36.9
• Patients Per Site: 11.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the safety, tolerability, bioactivity, and dose response of two different dosages (0.5 mg and 2.0 mg) of ranibizumab (RBZ) in patients with diabetic macular edema (DME).

Condition or Disease	Intervention/Treatment	Phase
Diabetic Macular Edema	Drug: Ranibizumab; Drug: ranibizumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 152 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Ranibizumab for Edema of the Macula in Diabetes: Protocol 3 With High Dose - the READ 3 Study
• Study Start Date: Feb 1, 2010
• Actual Primary Completion Date: Mar 1, 2012
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ranibizumab 0.5mg Intravitreal injections of ranibizumab 0.5mg dose for six monthly treatments then additional treatments with ranibizumab 0.5mg dose if the subject meets re-treatment criteria.	Drug: Ranibizumab; Intravitreal injections of ranibizumab 0.5mg dose for six monthly treatments then additional treatments with ranibizumab 0.5mg dose if the subject meets re-treatment criteria.; Other Names: lucentis
Experimental: Ranibizumab 2.0 mg Intravitreal injections of ranibizumab 2.0 mg dose for six monthly treatments then additional treatments with ranibizumab 2.0 mg dose if the subject meets re-treatment criteria.	Drug: ranibizumab; Intravitreal injections of ranibizumab 2.0 mg dose for six monthly treatments then additional treatments with ranibizumab 2.0 mg dose if the subject meets re-treatment criteria.; Other Names: lucentis high-dose

Outcome Measures

Primary Outcome Measures

1. Deaths Due to Myocardial Infarction [6 Months]

Secondary Outcome Measures

1. Mean Change in Best Corrected Visual Acuity From Baseline to Month 6 [baseline 6 Months]

   Mean change in best corrected visual acuity (BCVA) (ETDRS) at 4 meters in the study eye over time through month 6.

2. Mean Change in Retinal Thickness at Month 6 [baseline to6 Months]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

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

• Age ≥18 years

• Diagnosis of diabetes mellitus (type 1 or type 2)

• Serum HbA1c ≥ 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 fluorescein angiography and OCT images

• Foveal thickness of ≥ 250 μm,

• 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). The non-study eye must be ≥ 20 letters (approximate Snellen equivalent 20/400).

• 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 of decreased vision If a female of childbearing potential, a negative pregnancy test and commitment to the use of at least two forms of effective contraception (birth control) for the duration of the study are necessary.

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, bevacizumab, anecortave acetate, protein kinase C inhibitor, etc.) within 2 months of study entry

• Proliferative diabetic retinopathy in the study eye, with the exceptions of

• Inactive, fibrotic proliferative diabetic retinopathy that has regressed following panretinal 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 optical coherence tomography (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

• Cataract surgery in the study eye within 3 months of study entry; Yttrium-Aluminum- Garnet (YAG) laser capsulotomy within 1 month 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 ≥30 mm Hg despite treatment with anti-glaucoma medications)

• Blood pressure exceeding 180/100 (sitting) during the screening period

• Uncontrolled diabetes mellitus, as evidenced by glycosylated hemoglobin (HbA1c) value

13%

• Renal failure requiring dialysis or renal transplant

• Premenopausal women unwilling to commit to adequate contraception

• History of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use an investigational drug, might affect interpretation of the results of the study, or render the subject at high risk from treatment complications

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

• History of cerebral vascular accident, myocardial infarction, transient ischemic attacks within 3 months of study enrollment.

• Have a history of hypersensitivity to ranibizumab or any of its components

• Have the presence of active malignancy, including lymphoproliferative disorders. Subjects with a history of fully resolved basal or squamous cell skin cancer may be enrolled.

Other

• Inability to comply with study or follow-up procedures

• Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated.

• Participation in another simultaneous medical investigation or trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Retina Vitreous Associates	Beverly Hills	California	United States	90211
2	University of California San Diego	LaJolla	California	United States	92037
3	Doheny Eye Institute	Los Angeles	California	United States	90033
4	East Bay Retina Institute	Oakland	California	United States	94609
5	Retina Macula Institute	Torrance	California	United States	90503
6	Retina Group of Florida	Fort Lauderdale	Florida	United States	33334
7	Retina Institute of Hawaii	Honolulu	Hawaii	United States	96815
8	Illinois Retina Associates	Joliet	Illinois	United States	60435
9	University of Kansas	Prairie Village	Kansas	United States	66208
10	Johns Hopkins University Wilmer Eye Institute	Baltimore	Maryland	United States	21287
11	Eye Care Specialists	Kingston	Pennsylvania	United States	18704
12	Black Hills Eye Institute	Rapid City	South Dakota	United States	57701
13	Texas Retina Associates	Arlington	Texas	United States	76012

Sponsors and Collaborators

• Johns Hopkins University
• Juvenile Diabetes Research Foundation

Investigators

• Principal Investigator: Diana V 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: NCT01077401
• Other Study ID Numbers: NA_00034586
• First Posted: Mar 1, 2010
• Last Update Posted: Apr 28, 2017
• Last Verified: Mar 1, 2017

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

Study Results

Participant Flow

Arm/Group Title	Ranibizumab 0.5mg	Ranibizumab 2.0 mg
Arm/Group Description	Intravitreal injections of ranibizumab 0.5mg dose for six monthly treatments then additional treatments with ranibizumab 0.5mg dose if the subject meets re-treatment criteria. Ranibizumab: Intravitreal injections of ranibizumab 0.5mg dose for six monthly treatments then additional treatments with ranibizumab 0.5mg dose if the subject meets re-treatment criteria.	Intravitreal injections of ranibizumab 2.0 mg dose for six monthly treatments then additional treatments with ranibizumab 2.0 mg dose if the subject meets re-treatment criteria. ranibizumab: Intravitreal injections of ranibizumab 2.0 mg dose for six monthly treatments then additional treatments with ranibizumab 2.0 mg dose if the subject meets re-treatment criteria.
Period Title: Overall Study
STARTED	77	75
COMPLETED	59	54
NOT COMPLETED	18	21

Baseline Characteristics

Arm/Group Title	Ranibizumab 0.5mg	Ranibizumab 2.0 mg	Total
Arm/Group Description	Intravitreal injections of ranibizumab 0.5mg dose for six monthly treatments then additional treatments with ranibizumab 0.5mg dose if the subject meets re-treatment criteria. Ranibizumab: Intravitreal injections of ranibizumab 0.5mg dose for six monthly treatments then additional treatments with ranibizumab 0.5mg dose if the subject meets re-treatment criteria.	Intravitreal injections of ranibizumab 2.0 mg dose for six monthly treatments then additional treatments with ranibizumab 2.0 mg dose if the subject meets re-treatment criteria. ranibizumab: Intravitreal injections of ranibizumab 2.0 mg dose for six monthly treatments then additional treatments with ranibizumab 2.0 mg dose if the subject meets re-treatment criteria.	Total of all reporting groups
Overall Participants	77	75	152
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	64.8	63.5	64.1
Sex: Female, Male (Count of Participants)
Female	30 39%	37 49.3%	67 44.1%
Male	47 61%	38 50.7%	85 55.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	4 5.2%	5 6.7%	9 5.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	6 7.8%	13 17.3%	19 12.5%
White	45 58.4%	39 52%	84 55.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	22 28.6%	18 24%	40 26.3%
Region of Enrollment (participants) [Number]
United States	77 100%	75 100%	152 100%

Outcome Measures

1. Primary Outcome

Title	Deaths Due to Myocardial Infarction
Time Frame	6 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ranibizumab 0.5mg	Ranibizumab 2.0 mg
Arm/Group Description	Intravitreal injections of ranibizumab 0.5mg dose for six monthly treatments then additional treatments with ranibizumab 0.5mg dose if the subject meets re-treatment criteria. Ranibizumab: Intravitreal injections of ranibizumab 0.5mg dose for six monthly treatments then additional treatments with ranibizumab 0.5mg dose if the subject meets re-treatment criteria.	Intravitreal injections of ranibizumab 2.0 mg dose for six monthly treatments then additional treatments with ranibizumab 2.0 mg dose if the subject meets re-treatment criteria. ranibizumab: Intravitreal injections of ranibizumab 2.0 mg dose for six monthly treatments then additional treatments with ranibizumab 2.0 mg dose if the subject meets re-treatment criteria.
Measure Participants	77	75
Number [participants]	1 1.3%	3 4%

2. Secondary Outcome

Title	Mean Change in Best Corrected Visual Acuity From Baseline to Month 6
Description	Mean change in best corrected visual acuity (BCVA) (ETDRS) at 4 meters in the study eye over time through month 6.
Time Frame	baseline 6 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ranibizumab 0.5mg	Ranibizumab 2.0 mg
Arm/Group Description	Intravitreal injections of ranibizumab 0.5mg dose for six monthly treatments then additional treatments with ranibizumab 0.5mg dose if the subject meets re-treatment criteria. Ranibizumab: Intravitreal injections of ranibizumab 0.5mg dose for six monthly treatments then additional treatments with ranibizumab 0.5mg dose if the subject meets re-treatment criteria.	Intravitreal injections of ranibizumab 2.0 mg dose for six monthly treatments then additional treatments with ranibizumab 2.0 mg dose if the subject meets re-treatment criteria. ranibizumab: Intravitreal injections of ranibizumab 2.0 mg dose for six monthly treatments then additional treatments with ranibizumab 2.0 mg dose if the subject meets re-treatment criteria.
Measure Participants	77	75
Mean (Standard Deviation) [letters]	9.34 (10.34)	7.04 (8.33)

3. Secondary Outcome

Title	Mean Change in Retinal Thickness at Month 6
Time Frame	baseline to6 Months

Outcome Measure Data

Analysis Population Description

Data was not collected for 4 participants in the Ranibizumab 0.5mg group for this outcome measure.

Arm/Group Title	Ranibizumab 0.5mg	Ranibizumab 2.0 mg
Arm/Group Description	Intravitreal injections of ranibizumab 0.5mg dose for six monthly treatments then additional treatments with ranibizumab 0.5mg dose if the subject meets re-treatment criteria. Ranibizumab: Intravitreal injections of ranibizumab 0.5mg dose for six monthly treatments then additional treatments with ranibizumab 0.5mg dose if the subject meets re-treatment criteria.	Intravitreal injections of ranibizumab 2.0 mg dose for six monthly treatments then additional treatments with ranibizumab 2.0 mg dose if the subject meets re-treatment criteria. ranibizumab: Intravitreal injections of ranibizumab 2.0 mg dose for six monthly treatments then additional treatments with ranibizumab 2.0 mg dose if the subject meets re-treatment criteria.
Measure Participants	73	75
Mean (Standard Deviation) [µm]	168.57 (145.67)	159.69 (124.50)

Adverse Events

Time Frame	6 months
Arm/Group Title	Ranibizumab 0.5mg		Ranibizumab 2.0 mg
Arm/Group Description	Intravitreal injections of ranibizumab 0.5mg dose for six monthly treatments then additional treatments with ranibizumab 0.5mg dose if the subject meets re-treatment criteria. Ranibizumab: Intravitreal injections of ranibizumab 0.5mg dose for six monthly treatments then additional treatments with ranibizumab 0.5mg dose if the subject meets re-treatment criteria.		Intravitreal injections of ranibizumab 2.0 mg dose for six monthly treatments then additional treatments with ranibizumab 2.0 mg dose if the subject meets re-treatment criteria. ranibizumab: Intravitreal injections of ranibizumab 2.0 mg dose for six monthly treatments then additional treatments with ranibizumab 2.0 mg dose if the subject meets re-treatment criteria.
All Cause Mortality
	Ranibizumab 0.5mg		Ranibizumab 2.0 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ranibizumab 0.5mg		Ranibizumab 2.0 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/77 (1.3%)		3/75 (4%)
Cardiac disorders
Deaths from Myocardial Infarction within 6 months of starting study	1/77 (1.3%)	1	3/75 (4%)	3
Other (Not Including Serious) Adverse Events
	Ranibizumab 0.5mg		Ranibizumab 2.0 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/77 (1.3%)		0/75 (0%)
Eye disorders
Loss of 30 or more letters	1/77 (1.3%)	1	0/75 (0%)	0

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.