Canadian Treat and Extend Analysis Trial With Ranibizumab (CAN-TREAT)

This is an observational study to will evaluate and compare two Ranibizumab treatment regimens (Standard of care) in patients with neovascular (wet) age-related macular degeneration (wAMD) aiming to achieve and to maintain a maximum visual function benefit. The results will be used to generate further recommendations on the timing of treatment administration for patients with neovascular (wet) age-related macular degeneration (wAMD). In this context, the study will use the anatomical imaging (for example, optical coherence tomography [OCT]) to evaluate wAMD disease activity impacted by the recurrence of disease instability and for decision making in the treatment decision algorithm.

Study Overview

• Status: Completed
• Conditions: wetAMD
• Intervention / Treatment: Other: 0.5 mg Ranibizumab intravitreal injections

• Study Type: Observational
• Enrollment (Actual): 505

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2H0C8
      • Novartis Investigative Site
    • Edmonton, Alberta, Canada, T5H 0X5
      • Novartis Investigative Site
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 4B7
      • Novartis Investigative Site
  • Newfoundland and Labrador
    • St Johns, Newfoundland and Labrador, Canada, A1A 4A5
      • Novartis Investigative Site
    • St Johns, Newfoundland and Labrador, Canada, A1B 1S1
      • Novartis Investigative Site
  • Ontario
    • Brampton, Ontario, Canada, L6Y 0P6
      • Novartis Investigative Site
    • Hamilton, Ontario, Canada, L8G 5E4
      • Novartis Investigative Site
    • London, Ontario, Canada, N6A 4G5
      • Novartis Investigative Site
    • Missisauga, Ontario, Canada, L5L 1W8
      • Novartis Investigative Site
    • Ottawa, Ontario, Canada, K1H 8L6
      • Novartis Investigative Site
    • Timmins, Ontario, Canada, P4N 0A2
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M4N 3M5
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M5T 2S8
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M5C 2T2
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M3C 0G9
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M5V 1H6
      • Novartis Investigative Site
  • Quebec
    • Boisbriand, Quebec, Canada, J7H 1S6
      • Novartis Investigative Site
    • Drummondville, Quebec, Canada, J2C 2C4
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H3Z 1P4
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H4P 2S4
      • Novartis Investigative Site
    • Sherbrooke, Quebec, Canada, J1J 2B8
      • Novartis Investigative Site
    • Sherbrooke, Quebec, Canada, J1J 2E8
      • Novartis Investigative Site
    • Ste-Foy, Quebec, Canada, G1V 1T6
      • Novartis Investigative Site
    • Thetford Mines, Quebec, Canada, G6G 2V2
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 50 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The study population will consist of male and female Canadian patients diagnosed with visual impairment due to wAMD and for whom Ranibizumab has been prescribed as their standard of care by the treating physician. Eligibility for Ranibizumab will be determined by the study physician according to the current prescribing information. A total of 580 patients will be enrolled from approximately 20 to 25 centers.

Description

Inclusion Criteria:

• Infomed consent,
• Male and Female, 50 years of age or older
• Diagnosis of treatment-naive CNV secondary to age-related macular degeneration(AMD) in the study eye,
• BCVA score between 78 and 19 letters inclusive,

Exclusion Criteria:

• Patients with structural foveal damage in the study eye,
• Patients with confounding severe oculare diseases,
• Patients with suspicion of ( Polypoidal Choroidal Vasculapathy PCV) in the study eye,
• Patients with active or suspected or periocular infections in either eye or active intraocular inflammation in either eye,
• Patients who had previous subfoveal laser photocoagulation in the study eye or history of vitrectomy surgery in the study eye,
• Patients who had any prior treatment in the study eye, e.g., with Visudyne*, Avastin*, prior Ranibizumab treatment, Ozurdex*, external radiation therapy, transpupillary thermotherapy (TTT), or any intravitreal injection,
• Patients with a known sensitivity to Ranibizumab or any component of its formulation,
• Patients who have used any investigational agent in the last 30 days,
• Concurrent participation in a clinical trial or within 30 days prior to enrollment,
• Patients having received systemic treatment with any other anti-vascular endothelial growth factor (VEGF) therapy ≤ 60 days prior to enrollment
• Patients with physical or mental disabilities that prevent accurate vision testing,
• Patients physically unable to tolerate intravenous fluorescein angiography,
• Pregnant or breastfeeding female patients,
• Any patient with recent history of new onset cardiac disease or thromboembolic central nervous system (CNS) event (within 12 months of Baseline Visit),
• Patients with any other condition which, in the opinion of the Investigator, would require treatment that would significantly impact the treatment assessments during this study.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Arm 1 (Monthly); 0.5 mg intravitreal injections of Ranibizumab monthly for the duration of the study.	Other: 0.5 mg Ranibizumab intravitreal injections; All eligible patients will initially be treated in a fixed loading phase, consisting of one intravitreal injection of Ranibizumab 0.5 mg per month for 3 consecutive months (Day 1, Month 1, and Month 2). After the loading phase, patients will be treated according to the treatment arm to which they have been assigned, either a continued once monthly dosing regimen, or an extended schedule of Ranibizumab intravitreal injections as described below. The planned duration of total treatment is 24 months.
Arm 2 (Treat and Extend); Three consecutive months of 0.5 mg Ranibizumab intravitreal injections (Day 1, Month 1, and Month 2). Monthly injections will continue until evidence of disease stability is observed. Specifically, monthly treatment will continue until visual acuity is deemed stable as indicated by a gain in visual acuity of ≤ 3 ETDRS letters from the prior month, no clinical evidence of lesion growth, fluid or blood, and no intraretinal or subretinal fluid on OCT. When this is achieved, the intervals between each subsequent injection will be extended by 2 weeks (intervals of 6 weeks, 8 weeks, 10 weeks, to a maximum of 12 weeks) until clinical or diagnostic evidence of disease instability is observed based on OCT findings and/or BCVA ETDRS.	Other: 0.5 mg Ranibizumab intravitreal injections; All eligible patients will initially be treated in a fixed loading phase, consisting of one intravitreal injection of Ranibizumab 0.5 mg per month for 3 consecutive months (Day 1, Month 1, and Month 2). After the loading phase, patients will be treated according to the treatment arm to which they have been assigned, either a continued once monthly dosing regimen, or an extended schedule of Ranibizumab intravitreal injections as described below. The planned duration of total treatment is 24 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Visual Acuity	Visual Acuity (VA) will be assessed using best correction determined from protocol refraction during screening and every 3 months throughout the study; in the monthly regimen and during screening and at every visit thereafter throughout the study in the treat and extend regimen. VA measurements (number of letters correctly identified) will be performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like VA testing charts at an initial testing distance of 4 meters. This outcome measure will describe the difference in the VA mean changes between the two regimens from Baseline to Month 12.	Baseline to Month 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with a gain of equal or more than 5, 10, and 15 letters between the 2 treatment arms.	Baseline to Month 12
Proportion of patients with a gain of equal or more than 5, 10, and 15 letters between the 2 treatment arms.	Baseline to Month 24
Proportion of patients with a loss of less than 5, 10, and 15 letters between the 2 treatment arms from baseline to Month 12 and from baseline to Month 24.	baseline to Month 12
Proportion of patients with a loss of less than 5, 10, and 15 letters between the 2 treatment arms.	baseline to Month 24
Mean change in BCVA ETDRS between the 2 treatment arms at Month 12 compared to Month 3.	Month 12 and Month 3
Mean change in BCVA ETDRS between the 2 treatment arms.	Baseline to Month 24
Number of injections performed in each treatment arms.	Baseline to Month 24
Number of injections performed in each treatment arms.	Month 12 to Month 24

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Kertes PJ, Galic IJ, Greve M, Williams G, Baker J, Lahaie M, Sheidow T. Efficacy of a Treat-and-Extend Regimen With Ranibizumab in Patients With Neovascular Age-Related Macular Disease: A Randomized Clinical Trial. JAMA Ophthalmol. 2020 Mar 1;138(3):244-250. doi: 10.1001/jamaophthalmol.2019.5540.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 8, 2013
• Primary Completion (ACTUAL): July 31, 2019
• Study Completion (ACTUAL): July 31, 2019

Study Registration Dates

• First Submitted: February 18, 2014
• First Submitted That Met QC Criteria: April 2, 2014
• First Posted (ESTIMATE): April 4, 2014

Study Record Updates

• Last Update Posted (ACTUAL): June 5, 2020
• Last Update Submitted That Met QC Criteria: June 3, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Ranibizumab; Lucentis; Age related macular degeneration; wetAMD; Treat and Extend
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: CRFB002ACA06