Study of Efficacy of Ranibizumab in Different Regimens in Patients With Diabetic Macula Edema (DIVERSE)

A 12-months, Randomized, VA-assessor Blinded, Multicenter, Controlled Phase IV Trial to Investigate Noninferiority of Two Treatment Algorithms (Discretion of the Investigator vs. Pro re Nata) of 0.5 mg Ranibizumab in Patients With Visual Impairment Due to Diabetic Macula Edema

The purpose of this study was to demonstrate that the change of best corrected visual acuity (BCVA) was comparable in patients treated with ranibizumab at the discretion of the investigator vs. treatment according to a standard of care scheme (pro re nata, as needed).

Study Overview

• Status: Completed
• Conditions: Diabetic Retinopathy
• Intervention / Treatment: Drug: ranibizumab 0.5 mg

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Ahaus, Germany, 48683
    • Novartis Investigative Site
  • Bayreuth, Germany, 95444
    • Novartis Investigative Site
  • Berlin, Germany, 12203
    • Novartis Investigative Site
  • Berlin, Germany, 14169
    • Novartis Investigative Site
  • Bonn, Germany, 53127
    • Novartis Investigative Site
  • Dresden, Germany, 01067
    • Novartis Investigative Site
  • Duesseldorf, Germany, 40225
    • Novartis Investigative Site
  • Düsseldorf, Germany, 40212
    • Novartis Investigative Site
  • Freiburg I. Br, Germany, 79106
    • Novartis Investigative Site
  • Gottingen, Germany, 37075
    • Novartis Investigative Site
  • Greifswald, Germany, 17475
    • Novartis Investigative Site
  • Halle, Germany, 06114
    • Novartis Investigative Site
  • Hamburg, Germany, 20246
    • Novartis Investigative Site
  • Hösbach, Germany, 63768
    • Novartis Investigative Site
  • Kempten, Germany, 87435
    • Novartis Investigative Site
  • Koeln, Germany, 50924
    • Novartis Investigative Site
  • Koeln, Germany, 50935
    • Novartis Investigative Site
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
  • Ludwigshafen, Germany, 67063
    • Novartis Investigative Site
  • Lübeck, Germany, 23538
    • Novartis Investigative Site
  • Magdeburg, Germany, 39108
    • Novartis Investigative Site
  • Marburg, Germany, 35043
    • Novartis Investigative Site
  • Muenster, Germany, 48149
    • Novartis Investigative Site
  • Muenster, Germany, 48145
    • Novartis Investigative Site
  • München, Germany, 81675
    • Novartis Investigative Site
  • München, Germany, 80333
    • Novartis Investigative Site
  • Stuttgart, Germany, 70174
    • Novartis Investigative Site
  • Tübingen, Germany, 72076
    • Novartis Investigative Site
  • Ulm, Germany, 89075
    • Novartis Investigative Site
  • Wurzburg, Germany, 97080
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with Type 1 or Type 2 diabetes mellitus with glycosylated hemoglobin (HbA1c) ≤ 12.0%
• Patients with visual impairment due to DME in at least one eye
• BCVA ≥ 24 and ≤ 78 letters in the study eye

Exclusion Criteria:

• Active intraocular inflammation
• Any active infection in either eye at the
• Structural damage within 0.5 disc diameter of the center of the macula in the study eye
• Uncontrolled glaucoma in either eye at screening

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Discretion of the investigator (DI); ranibizumab 0.5 mg, after initial monthly treatment until maximum BCVA and no signs or no further change of disease activity, the investigator treated patients at their own discretion. There were no strict recommendations for retreatment or scheduling of upcoming visits.	Drug: ranibizumab 0.5 mg; intravitreal injection; Other Names: Lucentis
Active Comparator: Pro re nata (PRN); ranibizumab 0.5 mg, after initial monthly therapy until maximum BCVA and no signs or no further improvement of disease activity, patients were monitored every month and retreated if any signs of disease activity occurred	Drug: ranibizumab 0.5 mg; intravitreal injection; Other Names: Lucentis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Average Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye From Month 1 to Study Treatment Completion (Month 12)	BCVA was assessed as letters read using Early Treatment Diabetic Retinopathy Study (ETDRS) charts. The mean average change from baseline was defined as the difference between the average level of BCVA (ETDRS letters) over all post-baseline assessments from Month 1 to Month 12. A positive change represents an improvement in visual acuity	Baseline, Month 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Visits	Mean number of visits during the study	Baseline to Month 12
Number of Injections	mean number of injections in the study eye during the study	Baseline to Month 12
Number of Treatment Free Intervals	A treatment-free interval is the interval between the first NO treatment given when the reason for NO treatment given is one of the three stability criteria and the first subsequent YES treatment given after that.	Baseline to Month 12
Mean Change in Central Subfield Retinal Thickness (CSRT)	Evaluated by central reading center assessing OCT images	Baseline to Month 12
Mean Change of Foveal Center Point Thickness	Evaluated by central reading center assessing OCT images	Baseline to Month 12
Number of Participants With Change in Diabetic Retinopathy Study (DRS) Retinopathy Scale	Evaluated by central reading center scoring fundus photography	Baseline to Month 12

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2015
• Primary Completion (Actual): June 8, 2017
• Study Completion (Actual): June 8, 2017

Study Registration Dates

• First Submitted: January 12, 2015
• First Submitted That Met QC Criteria: February 11, 2015
• First Posted (Estimate): February 19, 2015

Study Record Updates

• Last Update Posted (Actual): January 4, 2019
• Last Update Submitted That Met QC Criteria: January 1, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Diabetic macular edema; Visual impairment
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Endocrine System Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Retinal Diseases; Diabetic Retinopathy; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: CRFB002DDE26; 2014-002854-37 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No