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

• ClinicalTrials.gov Identifier: NCT01775124
• Recruitment Status: Completed
• First Posted: January 24, 2013
• Results First Posted: February 12, 2018
• Last Update Posted: September 4, 2019
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Neovascular Age-related Macular Degeneration	Drug: Ranibizumab	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 332 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: February 22, 2013
• Actual Primary Completion Date: November 23, 2015
• Actual Study Completion Date: November 23, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Average Change in Visual Acuity (Letters) From Month 3 to Month 4 Through Month 12 [ Time Frame: 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.

Secondary Outcome Measures :

1. Average Visual Acuity Change (Letters) From Month 3 to Month 4 Through Month 24 [ Time Frame: 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.
2. Average Visual Acuity Change From Baseline to Month 1 Through Month 12 and Month 1 Through Month 24 [ Time Frame: Baseline to 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
3. Change From Baseline in Visual Acuity (Letters) of the Study Eye Over Time [ Time Frame: Baseline to 24 months ]
   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
4. Number of Patients With a BCVA Improvement of ≥5, ≥10, ≥15, and ≥30 Letters From Baseline to Month 24 [ Time Frame: 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.
5. Number of Patients With a BCVA Loss of 15 Letters in the Study Eye Over Time [ Time Frame: Baseline to 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 for each post-baseline month whether or not a patient lost less than 15 letters of VA as compared with baseline.
6. Number of Patients With a Best Corrected Visual Acuity (BCVA) of More of 73 Letters or More [ Time Frame: Month 12 and 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 for Month 12 and Month 24 whether a patient had a VA score of 73 or more letters
7. Change From Baseline in Central Sub-Field Thickness (CSFT) of the Study Eye Over Time to Month 12 and Month 24 [ Time Frame: Baseline to 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
8. Duration of Ranibizumab Treatment Free Interval in the Study Eye up to Month 24 [ Time Frame: 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
9. Duration of Ranibizumab Treatment Free Interval in the Study Eye Prior to Month 12 [ Time Frame: 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.
10. Duration of Active Treatment Phase Prior to Month 12 [ Time Frame: Prior to month 12 ]
11. Duration of Active Treatment Phase up to Month 24 [ Time Frame: up to month 24 ]

Eligibility Criteria

• Ages Eligible for Study: 50 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

China, Beijing

Novartis Investigative Site

Beijing, Beijing, China, 100191

Novartis Investigative Site

Beijing, Beijing, China, 100730

China, Chongqing

Novartis Investigative Site

Chongqing City, Chongqing, China, 400042

China, Gansu

Novartis Investigative Site

Lanzhou, Gansu, China, 730030

China, Heilongjiang

Novartis Investigative Site

Harbin, Heilongjiang, China, 150001

China, Hubei

Novartis Investigative Site

Wuhan, Hubei, China, 430060

Novartis Investigative Site

Wuhan, Hubei, China, 430070

China, Hunan

Novartis Investigative Site

Changsha City, Hunan, China, 410011

China, Jiangsu

Novartis Investigative Site

Nanjing, Jiangsu, China, 210029

China, Jiangxi

Novartis Investigative Site

Nanchang, Jiangxi, China, 330006

China, Liaoning

Novartis Investigative Site

Shenyang, Liaoning, China, 110011

China, Shandong

Novartis Investigative Site

Qingdao, Shandong, China, 2666000

China, Shanxi

Novartis Investigative Site

Taiyuan, Shanxi, China, 030002

China, Sichuan

Novartis Investigative Site

Chengdu, Sichuan, China, 610041

China, Tianjin

Novartis Investigative Site

Tianjin, Tianjin, China, 300020

Novartis Investigative Site

Tianjin, Tianjin, China, 300070

China, Zhejiang

Novartis Investigative Site

Wenzhou, Zhejiang, China, 325027

China

Novartis Investigative Site

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

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01775124
• Other Study ID Numbers: CRFB002A2413
• First Posted: January 24, 2013
• Results First Posted: February 12, 2018
• Last Update Posted: September 4, 2019
• Last Verified: August 2019

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Macular degeneration,; age-related macular degeneration (ARMD),; vision loss,; macula damage,; retina damage,; dry macular degeneration,; wet macular degeneration,; AMD

Additional relevant MeSH terms:

Macular Degeneration; Wet Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases; Ranibizumab; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antineoplastic Agents