Efficacy and Safety of Ranibizumab 0.5 mg Administered as Two Alternative Dosing Regimens in Chinese Patients With nAMD (Age Related Macular Degeneration) (DRAGON)

A 24-month, Randomized, Double-masked, Controlled, Multicenter Study Evaluating the Efficacy and Safety of Ranibizumab 0.5 mg Administered as Two Alternative Dosing Regimens in Chinese Patients With Neovascular Age Related Macular Degeneration (AMD)

The study evaluated the efficacy and safety of two different dosing regimens of ranibizumab (either monthly injections or injections as-needed based on the stability of a patient's vision) in Chinese patients with wet age-related macular degeneration (AMD) . This study was to provide long-term safety data in the treatment of Chinese patients with wet AMD.

Study Overview

• Status: Completed
• Conditions: Neovascular Age-related Macular Degeneration
• Intervention / Treatment: Drug: Ranibizumab

• Study Type: Interventional
• Enrollment (Actual): 332
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100044
    • Novartis Investigative Site
  • Beijing, China, 100176
    • Novartis Investigative Site
  • Chongqing, China, 400038
    • Novartis Investigative Site
  • Shanghai, China, 200031
    • Novartis Investigative Site
  • Shanghai, China, 200080
    • Novartis Investigative Site
  • Shanghai, China, 200092
    • Novartis Investigative Site
  • Beijing
    • Beijing, Beijing, China, 100730
      • Novartis Investigative Site
    • Beijing, Beijing, China, 100191
      • Novartis Investigative Site
  • Chongqing
    • Chongqing City, Chongqing, China, 400042
      • Novartis Investigative Site
  • Gansu
    • Lanzhou, Gansu, China, 730030
      • Novartis Investigative Site
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • Novartis Investigative Site
  • Hubei
    • Wuhan, Hubei, China, 430060
      • Novartis Investigative Site
    • Wuhan, Hubei, China, 430070
      • Novartis Investigative Site
  • Hunan
    • Changsha City, Hunan, China, 410011
      • Novartis Investigative Site
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Novartis Investigative Site
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Novartis Investigative Site
  • Liaoning
    • Shenyang, Liaoning, China, 110011
      • Novartis Investigative Site
  • Shandong
    • Qingdao, Shandong, China, 2666000
      • Novartis Investigative Site
  • Shanxi
    • Taiyuan, Shanxi, China, 030002
      • Novartis Investigative Site
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Novartis Investigative Site
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Novartis Investigative Site
    • Tianjin, Tianjin, China, 300070
      • Novartis Investigative Site
  • Zhejiang
    • Wenzhou, Zhejiang, China, 325027
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion criteria:

• Patients with visual impairment due to neovascular AMD
• A qualifying vision score at study entry Key Exclusion criteria
• Active infection or inflammation either eye at study entry
• Uncontrolled glaucoma in either eye
• Any disorder in the study eye which may affect vision
• Use of any systemic anti-vascular endothelial growth factor (VEGF)-drugs within 3 months prior to study entry
• Previous treatment of the study eye for wet AMD
• Any surgery in the study eye 3 months prior to or planned with 6 month after study entry

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ranibizumab 0.5 mg monthly; Monthly intravitreal injections of ranibizumab 0.5 mg in the core treatment period and PRN intravitreal injections of the same dose guided by best-corrected visual acuity (BCVA) stabilization in the extension treatment period	Drug: Ranibizumab; Intravitreal injections of 0.5 mg Ranibizumab
EXPERIMENTAL: Ranibizumab 0.5 mg pro re nata (PRN); PRN intravitreal injections of ranibizumab 0.5 mg guided by best-corrected visual acuity (BCVA) stabilization in the 23 month treatment period	Drug: Ranibizumab; Intravitreal injections of 0.5 mg Ranibizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Change in Visual Acuity (Letters) From Month 3 to Month 4 Through Month 12	Visual acuity (VA) was assessed at every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like VA testing charts at a testing distance of 4 meters. This outcome measure describes the difference between the VA averaged across all visits from Month 4 through 12 and the Month 3 Level of Visual Acuity (Letters) of the Study Eye. The treatment regimen up to Month 3 is the same in both treatment groups.	Month 3 to month 4 through Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Visual Acuity Change (Letters) From Month 3 to Month 4 Through Month 24	Visual acuity (VA) was assessed at every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters. This outcome measure describes the difference between the average level of VA over all monthly post-baseline assessments from Month 4 to Month 24 and the Month 3 Level of VA. The treatment regimen up to Month 3 is the same in both treatment groups.	Month 3 to month 4 through Month 24
Average Visual Acuity Change From Baseline to Month 1 Through Month 12 and Month 1 Through Month 24	Visual acuity (VA) was assessed at every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters. This outcome measure describes the difference between VA averaged across all visits from Month 1 through Month 12 (24) and the baseline VA level	Baseline to Month 24
Change From Baseline in Visual Acuity (Letters) of the Study Eye Over Time	Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters. This outcome measure describes the change in visual acuity at each visit compared to baseline	Baseline to 24 months
Number of Patients With a BCVA Improvement of ≥5, ≥10, ≥15, and ≥30 Letters From Baseline to Month 24	Visual acuity (VA) was at every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters. This outcome measure describes for each post-baseline month whether or not a patient improved by equal or more than 5, 10, 15,or 30 letters of VA as compared to baseline.	Baseline to Month 24
Number of Patients With a BCVA Loss of 15 Letters in the Study Eye Over Time	Visual acuity (VA) was assessed at every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters. This outcome measure describes for each post-baseline month whether or not a patient lost less than 15 letters of VA as compared with baseline.	Baseline to Month 24
Number of Patients With a Best Corrected Visual Acuity (BCVA) of More of 73 Letters or More	Visual acuity (VA) was assessed at every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters. This outcome measure describes for Month 12 and Month 24 whether a patient had a VA score of 73 or more letters	Month 12 and 24
Change From Baseline in Central Sub-Field Thickness (CSFT) of the Study Eye Over Time to Month 12 and Month 24	Optical coherence tomography(OCT) was used to assess CSFT (Central Sub-Field Thickness) representing the average retinal thickness of the circular area within 1 mm diameter around the foveal center. The Ns in the rows is the number of patients with a value for both baseline and the specific post-baseline visit	Baseline to Month 24
Duration of Ranibizumab Treatment Free Interval in the Study Eye up to Month 24	This outcome measure describes duration of treatment-free intervals. Treatment-free interval is defined as the number of visits (whether attended or not) where ranibizumab was not administered. n= the number of patients who had at least one ranibizumab treatment interruption	up to month 24
Duration of Ranibizumab Treatment Free Interval in the Study Eye Prior to Month 12	This outcome measure describes duration of treatment-free intervals prior to month 12. Treatment-free interval is defined as the number of visits (whether attended or not) where ranibizumab was not administered. n= the number of patients who had at least one ranibizumab treatment interruption Treatment-free interval is analyzed in the Ranibizumab 0.5 mg PRN group only. It is not analyzed in the Ranibizumab 0.5 mg monthly group because, by protocol design, these participants receive treatment monthly. Therefore, the analysis does not apply to this group.	prior to month 12
Duration of Active Treatment Phase Prior to Month 12		Prior to month 12
Duration of Active Treatment Phase up to Month 24		up to month 24

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 22, 2013
• Primary Completion (ACTUAL): November 23, 2015
• Study Completion (ACTUAL): November 23, 2015

Study Registration Dates

• First Submitted: January 22, 2013
• First Submitted That Met QC Criteria: January 22, 2013
• First Posted (ESTIMATE): January 24, 2013

Study Record Updates

• Last Update Posted (ACTUAL): September 4, 2019
• Last Update Submitted That Met QC Criteria: August 21, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: AMD; Macular degeneration,; age-related macular degeneration (ARMD),; vision loss,; macula damage,; retina damage,; dry macular degeneration,; wet macular degeneration,
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Wet Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: CRFB002A2413