Safety and Tolerability of Ranibizumab in Mono/Bilateral Wet Age Related Macular Degeneration (w-AMD) Patients in Eyes With BCVA<2/10 and/or 2nd Affected Eye (TWEYES)

A 12 Months, Prospective, Multicenter, Open-label, Single Arm Interventional Study Assessing the Safety and Tolerability of 0.5 mg Ranibizumab in Mono/Bilateral Wet AMD Patients in Eyes With (Best-Corrected Distance Visual Acuity) BCVA Below 2/10 and/or Second Affected Eye

The purpose of this study is to evaluate the safety and efficacy of ranibizumab in patients affected by wet age related macular degeneration (wAMD).

Study Overview

• Status: Completed
• Conditions: Wet Age Related Macular Degeneration
• Intervention / Treatment: Drug: ranibizumab

• Study Type: Interventional
• Enrollment (Actual): 1049
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Borgomanero, Italy, 28021
    • Novartis Investigative Site
  • Galliate, Italy, 28066
    • Novartis Investigative Site
  • Napoli, Italy, 80131
    • Novartis Investigative Site
  • Napoli, Italy, 80132
    • Novartis Investigative Site
  • Napoli, Italy, 80138
    • Novartis Investigative Site
  • Pozzuoli, Italy, 80078
    • Novartis Investigative Site
  • AL
    • Alessandria, AL, Italy, 15100
      • Novartis Investigative Site
    • Casale Monferrato, AL, Italy, 15033
      • Novartis Investigative Site
  • AN
    • Ancona, AN, Italy, 60126
      • Novartis Investigative Site
  • BA
    • Acquaviva delle Fonti, BA, Italy, 70021
      • Novartis Investigative Site
    • Putignano, BA, Italy, 70017
      • Novartis Investigative Site
    • Terlizzi, BA, Italy, 70038
      • Novartis Investigative Site
  • BG
    • Bergamo, BG, Italy, 24127
      • Novartis Investigative Site
  • BL
    • Belluno, BL, Italy, 32100
      • Novartis Investigative Site
  • BO
    • Bologna, BO, Italy, 40138
      • Novartis Investigative Site
  • BS
    • Brescia, BS, Italy, 25123
      • Novartis Investigative Site
    • Desenzano del Garda, BS, Italy, 25015
      • Novartis Investigative Site
  • BZ
    • Bolzano, BZ, Italy, 39100
      • Novartis Investigative Site
  • CA
    • Cagliari, CA, Italy, 09124
      • Novartis Investigative Site
  • CB
    • Larino, CB, Italy
      • Novartis Investigative Site
  • CE
    • Caserta, CE, Italy, 81100
      • Novartis Investigative Site
  • CH
    • Chieti, CH, Italy, 66100
      • Novartis Investigative Site
  • CN
    • Ceva, CN, Italy, 12073
      • Novartis Investigative Site
    • Cuneo, CN, Italy, 12100
      • Novartis Investigative Site
  • CO
    • Como, CO, Italy, 22100
      • Novartis Investigative Site
    • San Feramo Della Battaglia, CO, Italy, 22020
      • Novartis Investigative Site
  • CT
    • Acireale, CT, Italy, 95024
      • Novartis Investigative Site
    • Catania, CT, Italy, 95124
      • Novartis Investigative Site
    • Catania, CT, Italy, 95123
      • Novartis Investigative Site
  • CZ
    • Catanzaro, CZ, Italy, 88100
      • Novartis Investigative Site
  • FC
    • Forlì, FC, Italy, 47100
      • Novartis Investigative Site
  • FE
    • Cona, FE, Italy, 44100
      • Novartis Investigative Site
  • FG
    • Foggia, FG, Italy, 71100
      • Novartis Investigative Site
    • San Giovanni Rotondo, FG, Italy, 71013
      • Novartis Investigative Site
  • GE
    • Genova, GE, Italy, 16132
      • Novartis Investigative Site
    • Genova, GE, Italy, 16153
      • Novartis Investigative Site
    • Rapallo, GE, Italy, 16035
      • Novartis Investigative Site
  • KR
    • Crotone, KR, Italy, 88074
      • Novartis Investigative Site
  • LE
    • Tricase, LE, Italy, 73039
      • Novartis Investigative Site
  • LT
    • Terracina, LT, Italy, 04019
      • Novartis Investigative Site
  • ME
    • Messina, ME, Italy, 98125
      • Novartis Investigative Site
    • Milazzo, ME, Italy, 98057
      • Novartis Investigative Site
  • MI
    • Cinisello Balsamo, MI, Italy, 20092
      • Novartis Investigative Site
    • Legnano, MI, Italy, 20025
      • Novartis Investigative Site
    • Milano, MI, Italy, 20132
      • Novartis Investigative Site
    • Milano, MI, Italy, 20122
      • Novartis Investigative Site
    • Milano, MI, Italy, 20123
      • Novartis Investigative Site
    • Milano, MI, Italy, 20100
      • Novartis Investigative Site
    • Milano, MI, Italy, 20142
      • Novartis Investigative Site
    • Rozzano, MI, Italy, 20089
      • Novartis Investigative Site
    • Vizzolo Predabissi, MI, Italy, 20070
      • Novartis Investigative Site
  • NU
    • Nuoro, NU, Italy, 08100
      • Novartis Investigative Site
  • PA
    • Palermo, PA, Italy, 90127
      • Novartis Investigative Site
    • Palermo, PA, Italy, 90146
      • Novartis Investigative Site
  • PC
    • Piacenza, PC, Italy, 29100
      • Novartis Investigative Site
  • PD
    • Camposampiero, PD, Italy, 35012
      • Novartis Investigative Site
    • Monselice, PD, Italy, 35043
      • Novartis Investigative Site
    • Padova, PD, Italy, 35128
      • Novartis Investigative Site
    • Padova, PD, Italy, 35100
      • Novartis Investigative Site
  • PE
    • Pescara, PE, Italy, 65124
      • Novartis Investigative Site
  • PG
    • Citta' di Castello, PG, Italy, 06012
      • Novartis Investigative Site
    • Foligno, PG, Italy, 06034
      • Novartis Investigative Site
    • Perugia, PG, Italy, 06100
      • Novartis Investigative Site
  • PN
    • Pordenone, PN, Italy, 33170
      • Novartis Investigative Site
  • PR
    • Parma, PR, Italy, 43100
      • Novartis Investigative Site
  • PV
    • Pavia, PV, Italy, 27100
      • Novartis Investigative Site
  • RC
    • Reggio Calabria, RC, Italy, 89124
      • Novartis Investigative Site
  • RE
    • Correggio, RE, Italy, 42015
      • Novartis Investigative Site
    • Reggio Emilia, RE, Italy, 42123
      • Novartis Investigative Site
  • RM
    • Civitavecchia, RM, Italy, 00053
      • Novartis Investigative Site
    • Roma, RM, Italy, 00168
      • Novartis Investigative Site
    • Roma, RM, Italy, 00161
      • Novartis Investigative Site
    • Roma, RM, Italy, 00133
      • Novartis Investigative Site
    • Roma, RM, Italy, 00184
      • Novartis Investigative Site
    • Roma, RM, Italy, 00189
      • Novartis Investigative Site
    • Roma, RM, Italy, 00186
      • Novartis Investigative Site
  • RN
    • Riccione, RN, Italy, 47838
      • Novartis Investigative Site
  • SA
    • Eboli, SA, Italy, 84025
      • Novartis Investigative Site
    • Salerno, SA, Italy, 84131
      • Novartis Investigative Site
  • SO
    • Sondrio, SO, Italy, 23100
      • Novartis Investigative Site
  • SP
    • Sarzana, SP, Italy, 19038
      • Novartis Investigative Site
  • SS
    • Sassari, SS, Italy, 07100
      • Novartis Investigative Site
  • SV
    • Savona, SV, Italy, 17100
      • Novartis Investigative Site
  • TA
    • Taranto, TA, Italy, 74100
      • Novartis Investigative Site
  • TE
    • Teramo, TE, Italy, 64100
      • Novartis Investigative Site
  • TO
    • Torino, TO, Italy, 10122
      • Novartis Investigative Site
    • Torino, TO, Italy, 10153
      • Novartis Investigative Site
    • Torino, TO, Italy, 10152
      • Novartis Investigative Site
  • TR
    • Terni, TR, Italy, 05100
      • Novartis Investigative Site
  • TS
    • Trieste, TS, Italy, 34129
      • Novartis Investigative Site
  • TV
    • Conegliano, TV, Italy, 31015
      • Novartis Investigative Site
    • Treviso, TV, Italy, 31100
      • Novartis Investigative Site
  • UD
    • Udine, UD, Italy, 33100
      • Novartis Investigative Site
  • VA
    • Busto Arsizio, VA, Italy, 21052
      • Novartis Investigative Site
    • Somma Lombardo, VA, Italy, 21019
      • Novartis Investigative Site
    • Varese, VA, Italy, 21100
      • Novartis Investigative Site
  • VI
    • Santorso, VI, Italy, 36014
      • Novartis Investigative Site
    • Vicenza, VI, Italy, 36100
      • Novartis Investigative Site
  • VR
    • Legnago, VR, Italy, 37045
      • Novartis Investigative Site
    • Negrar, VR, Italy, 37024
      • Novartis Investigative Site
    • Verona, VR, Italy, 37126
      • 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

Inclusion Criteria

Male or female patients aged 50 years or above Willing and capable to provide informed written consent Eye(s) eligible for ranibizumab treatment, with a BCVA below 2/10 due to wet AMD and/or Second eye eligible for ranibizumab treatment, with first eye treated (currently or previously) with ranibizumab, whichever BCVA. In bilateral wAMD patients, the second eye can be included only if the first eye has been treated at least 14 days before with ranibizumab

Exclusion Criteria:

Active intraocular inflammation (grade trace or above) in either eye Any ocular or periocular active infection (current or suspected), e.g. conjunctivitis, keratitis, scleritis, uveitis, endophtalmitis, in either eye Risk factors for retinal pigment epithelial tear (including pigment epithelial retinal detachment) Ocular disorders that may confound interpretation of results compromise visual acuity or require medical or surgical intervention during the study period including cataract, retinal vascular occlusion, retinal detachment or macular hole Uncontrolled glaucoma in either eye (IOP ≥ 30 mmHg on medication or according to investigator's judgment) History of vitrectomy in the study eye History of stroke or transient ischemic attack Systemic treatment with any VEGF inhibitor in the 90 days prior to study enrollment Ocular treatment of the study eye with any anti-angiogenic drugs within 1 month prior to study enrollment Any intraocular surgery in the study eye within 28 days prior to enrollment Women of childbearing potential UNLESS using effective contraception during treatment Pregnant or lactating women Simultaneous participation in a study that includes administration of any investigational drug Known hypersensitivity to ranibizumab or any component of the ranibizumab formulation Inability to comply with study procedures.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Ranibizumab; Administered as an Intravitreal injection

Drug: ranibizumab; All patients will receive ranibizumab 0.5 mg/0.05 ml according to approved label: treatment is given monthly until maximum VA is achieved (i.e. stable VA for three consecutive monthly assessments performed while on ranibizumab treatment). Thereafter according to approved label, patients should be monitored monthly for visual acuity and treatment is to be resumed when monitoring indicates loss of visual acuity due to disease activity. Monthly injections should then be administered until stable visual acuity is reached again for three consecutive monthly assessments (implying a minimum of two injections).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Systemic Drug-related Adverse Events	Monitoring and recording all adverse events, including serious adverse events.	Baseline to Month 12
Number of Eyes With Ocular Drug-related Adverse Events	Monitoring and recording all adverse events, including serious adverse events.	Baseline to Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Number of Ranibizumab Injections		Baseline to month 12
Time Interval Between Injections in Bilateral Disease	Mean number of days between two consecutive injections per eye	Baseline to month 12
Mean Number of Injections Per Patient	Number of injections per patient	Baseline to month 12

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2014
• Primary Completion (Actual): June 15, 2016
• Study Completion (Actual): June 15, 2016

Study Registration Dates

• First Submitted: November 12, 2013
• First Submitted That Met QC Criteria: November 12, 2013
• First Posted (Estimate): November 19, 2013

Study Record Updates

• Last Update Posted (Actual): July 19, 2019
• Last Update Submitted That Met QC Criteria: May 11, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: macular degeneration; ranibizumab; wet AMD; eye disease; mono-bilateral; poor visual acuity; retinal disease; Angiogenesis Inhibitors; Angiogenesis Modulating Agents
• 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: CRFB002AIT02; 2013-003333-15 (EudraCT Number)

Plan for Individual participant data (IPD)

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

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

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