Ranibizumab for Recalcitrant Wet Age-related Macular Degeneration in Eyes Previously Switched From Bevacizumab and/or Ranibizumab to Aflibercept. (RESCUE)

The purpose of the study is to determine the effectiveness of Ranibizumab 0.5 mg or 1.0 mg in subjects who were previously treated with Bevacizumab and subsequently switched to Aflibercept. These subjects have demonstrated a sub-optimal therapeutic response to the previous therapies; therefore, the study aims to see if Ranibizumab may have a greater treatment effect.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Mountain View, California, United States, 94040
      • Northern California Retina Vitreous Associates

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

Inclusion Criteria:

• Ability to provide written informed consent and comply with study assessments for the full duration of the study
• Age greater than or equal to 50 years
• Best-corrected ETDRS VA between 20/25 to 20/320
• Total area of subretinal hemorrhage and/or fibrosis comprising less than 50% of lesion
• Any neovascular lesion type of ARMD having previously received at least 3 doses 1.25 mg of bevacizumab and/or ranibizumab (minimum 3 monthly injections) followed by 3 monthly doses of aflibercept 2.0 mg (with last injection being within 8 weeks) with evidence of recalcitrant ARMD, defined by at least one of the following: persistent subretinal fluid with or without intraretinal cystic edema on SD-OCT and/or leakage on fluorescein angiography

Exclusion Criteria:

• Pregnancy (positive pregnancy test) or lactation or pre-menopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD, or contraceptive hormone implant or patch
• 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
• History of prior vitrectomy surgery
• Previous treatment with photodynamic therapy, radiation, or any other intravitreal drug delivery, such as dexamethasone or triamcinolone
• Subretinal hemorrhage involving the central fovea > 1 disc area, subfoveal atrophy
• CNVM secondary to causes other than ARMD
• Previous retinal pigment epithelial tear

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ranibizumab 1 mg; Subjects will receive Ranibizumab 0.5 mg for 3 doses and then be separated into 2 arms based on initial response. In this Arm (Arm 1), patients will receive 1 mg of Ranibizumab monthly for the remainder of the study, if persistent or worse subretinal fluid with or without intraretinal cysts on SD-OCT is present.	Drug: Ranibizumab; Ranibizumab is formulated as a sterile solution and will be used in the case of an intervention.
Active Comparator: Ranibizumab 0.5 mg; Subjects will receive Ranibizumab 0.5 mg for 3 doses and then be separated into 2 arms based on initial response. In this Arm (Arm 2), patients will receive 0.5 mg of Ranibizumab monthly for the remainder of the study, if complete resolution of subretinal fluid on SD-OCT is present.	Drug: Ranibizumab; Ranibizumab is formulated as a sterile solution and will be used in the case of an intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean change in vision	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean change in BCVA	3 months, 9 months, and 12 months
Mean change in SD-OCT central foveal thickness	3 months, 6 months, 9 months, and 12 months
Percentage of recalcitrant patients that respond by either OCT or VA to Ranibizumab after not having a complete response to previous therapy	12 months
Percentage of patients that need to be escalated to 1 mg therapy	12 months

Collaborators and Investigators

• Sponsor: Northern California Retina Vitreous Associates
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Mark R Wieland, MD, Northern California Retina Vitreous Associates

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2013
• Primary Completion (Actual): July 1, 2018
• Study Completion (Actual): July 1, 2018

Study Registration Dates

• First Submitted: October 24, 2013
• First Submitted That Met QC Criteria: October 24, 2013
• First Posted (Estimate): October 30, 2013

Study Record Updates

• Last Update Posted (Actual): February 5, 2019
• Last Update Submitted That Met QC Criteria: February 1, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: ML28904