Clinical trial NCT01948830: Randomized Study for Efficacy and Safety of Ranibizumab 0.5mg in Treat-extend and Monthly Regimens in Patients With nAMD
Official title: A 12-month, Phase 3b, Randomized, Visual Acuity Assessor-masked, Multicenter Study Assessing the Efficacy and Safety of Ranibizumab 0.5mg in Treat and Extend Regimen Compared to Monthly Regimen, in Patients With Neovascular Age-related Macular Degeneration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Age-related Macular Degeneration
Choroidal Neovascularization
Keywords: Ranibizumab, Lucentis, choroidal neovascularization, age-related macular degeneration, treat and extend regimen
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2013-09-24
Enrollment: 650
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: This study was designed to evaluate the efficacy and safety of two different regimens of 0.5 mg ranibizumab given as intravitreal injection in patients with neovascular age-related macular degeneration

Detailed description: This was a 12-month, phase IIIb, randomized, Visual Acuity assessor-masked, multi-center, interventional study assessing the efficacy and safety of the TER vs monthly regimens of 0.5 mg ranibizumab intravitreal (IVT) injections in patients with newly diagnosed nAMD. Patients will be randomized 1:1 into one of two treatment arms, Treat and Extend or monthly regimens.

There will be 3 periods in this study: Screening period (up to 14days), treatment period (11 months), follow-up period (1 month). At randomization visit patients will be randomized into one of the 2 treatment groups Group I ranibizumab 0.5 mg based on monthly treatment or Group II ranibizumab 0.5 mg based on TER (randomization ratio of 1:1) and will receive the first dose of Investigational treatment. Patients in Group I the following visits will perform on monthly intervals. For patients in Group II the investigator will evaluate disease activity (i.e., signs of exudation) based on SD-OCT, and in case of absence of disease activity every next visit will be 2 weeks), with a maximum of a 12-week interval.

Eligibility criteria: Key Inclusion Criteria:

* Male or female patients, ≥50 years of age with signed informed consent before study procedures
* Visual impairment predominantly due to nAMD.
* Active CNV secondary to AMD confirmed by presence of active leakage from CNV seen by fluorescein angiography (FA) and/or color fundus photography
* Presence of intra- or subretinal fluid/hemorrhage seen by SD-OCT
* BCVA score must be ≤ 78 and ≥ 23 letters at 4 meters starting distance using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity charts (approximate Snellen equivalent of 20/32 and 20/320)

Key Exclusion Criteria:

* Any type of advanced, severe or unstable disease, including any medical condition (controlled or uncontrolled) that could be expected to progress, recur, or change to such an extent that it may bias the assessment of the clinical status of the patient to a significant degree or put the patient at special risk.
* Stroke or myocardial infarction within 3 months prior to Screening.
* Any active periocular or ocular infection or inflammation in both eyes.
* Ocular disorders in the study eye at the time of enrollment that may confound interpretation of study results and compromise visual acuity.
* Presence of amblyopia or amaurosis in the fellow eye.
* History of treatment with any anti-angiogenic drugs (including any anti- vascular endothelial growth factor (anti-VEGF) agents) e.g., bevacizumab \[Avastin®\], aflibercept \[Eylea®\]) or vPDT in the study eye.
* History of intravitreal treatment with corticosteroids within 6 months and history of intra-ocular surgery within 3 months in the study eye prior to the Screening.
* Pregnant or nursing (lactating) women. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment.

Primary outcomes:
measure: Change in Best Corrected Visual Acuity (BCVA) From Baseline to Month 12
timeFrame: Baseline to month 12
Secondary outcomes:
measure: Number of Visits Scheduled
timeFrame: From Month1 to Month 11
measure: Change in BCVA From Baseline to Month 12
timeFrame: Baseline to Month 12
measure: Average BCVA Change From Baseline to Month 12
timeFrame: Baseline and every month for 12 months
measure: Mean Change in Visual Acuity BCVA (Letters) From Baseline to Month 12
timeFrame: Baseline and every month for 12 months
measure: Number of Patients With a BCVA Improvement of ≥1, ≥5, ≥10, ≥15, and ≥30 Letters From Baseline to Month 12
timeFrame: Baseline and every month for 12 months
measure: Number of Patients With Best Corrected Visual Acuity (BCVA) Loss <5, <10, and <15 Letters by Visit
timeFrame: Baseline and every month for 12 months
measure: Number of Patients With a BCVA Value of ≥ 73 Letters (Approximate 20/40 Snellen Chart Equivalent) at Month 12
timeFrame: Baseline and every month for 12 months
measure: The Mean Number of Treatment Frequency
timeFrame: Month 12
measure: The Average Number of Days Between Injections
timeFrame: Month 12
measure: Percentage of Participants With Fluid Free Macula Over Time up to Month 12
timeFrame: Month 12
measure: Change in Central Subfield Retinal Thickness (CSFT) Over Time
timeFrame: Month 12
measure: Percentage of Patients With Choroidal Neovascularization (CNV) Leakage Assessed by Fluorescein Angiography (FA) in the Study Eye at
timeFrame: Month 12
measure: Change From Baseline in Composite Score of the National Eye Institute-Visual Function Questionnaire-25 (NEI-VFQ-25)
timeFrame: Baseline, Month 12
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: Novartis Investigative Site
city: Ottignies
country: Belgium
facility: Novartis Investigative Site
city: Zottegem
country: Belgium
facility: Novartis Investigative Site
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Zagreb
country: Croatia
facility: Novartis Investigative Site
city: Glostrup
country: Denmark
facility: Novartis Investigative Site
city: Roskilde
country: Denmark
facility: Novartis Investigative Site
city: Cairo
country: Egypt
facility: Novartis Investigative Site
state: Abbassia
city: Cairo
country: Egypt
facility: Novartis Investigative Site
city: Ahaus
country: Germany
facility: Novartis Investigative Site
city: Augsburg
country: Germany
facility: Novartis Investigative Site
city: Chemnitz
country: Germany
facility: Novartis Investigative Site
city: Darmstadt
country: Germany
facility: Novartis Investigative Site
city: Göttingen
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Karlsruhe
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Ludwigshafen
country: Germany
facility: Novartis Investigative Site
city: Magdeburg
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Siegburg
country: Germany
facility: Novartis Investigative Site
city: Stuttgart
country: Germany
facility: Novartis Investigative Site
city: Sulzbach
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Pécs
country: Hungary
facility: Novartis Investigative Site
city: Szeged
country: Hungary
facility: Novartis Investigative Site
city: Zalaegerszeg
country: Hungary
facility: Novartis Investigative Site
city: Bangalore
country: India
facility: Novartis Investigative Site
state: Karnataka
city: Chennai
country: India
facility: Novartis Investigative Site
state: Tamil Nadu
city: Vanchiyoor
country: India
facility: Novartis Investigative Site
state: Thiruvanantapuram
city: Haifa
country: Israel
facility: Novartis Investigative Site
city: Jerusalem
country: Israel
facility: Novartis Investigative Site
city: Petach Tikva
country: Israel
facility: Novartis Investigative Site
city: Rehovot
country: Israel
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Padova
country: Italy
facility: Novartis Investigative Site
state: PD
city: Pisa
country: Italy
facility: Novartis Investigative Site
state: PI
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Sassari
country: Italy
facility: Novartis Investigative Site
state: SS
city: Udine
country: Italy
facility: Novartis Investigative Site
state: UD
city: Seongnam
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gyeonggi
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Busan
country: Korea, Republic of
facility: Novartis Investigative Site
city: Coimbra
country: Portugal
facility: Novartis Investigative Site
city: Coimbra
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Porto
country: Portugal
facility: Novartis Investigative Site
city: Vila Franca de Xira
country: Portugal
facility: Novartis Investigative Site
city: Kazan
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Novosibirsk
country: Russian Federation
facility: Novartis Investigative Site
city: Samara
country: Russian Federation
facility: Novartis Investigative Site
city: Banska Bystrica
country: Slovakia
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Nove Zamky
country: Slovakia
facility: Novartis Investigative Site
city: Poprad
country: Slovakia
facility: Novartis Investigative Site
city: Zilina
country: Slovakia
facility: Novartis Investigative Site
city: Ljubljana
country: Slovenia
facility: Novartis Investigative Site
city: Oviedo
country: Spain
facility: Novartis Investigative Site
state: Asturias
city: Valladolid
country: Spain
facility: Novartis Investigative Site
state: Castilla y Leon
city: Sant Cugat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Zaragoza
country: Spain
facility: Novartis Investigative Site
city: Bern
country: Switzerland
facility: Novartis Investigative Site
city: Bern
country: Switzerland
facility: Novartis Investigative Site
city: Lausanne
country: Switzerland
facility: Novartis Investigative Site
city: Zuerich
country: Switzerland
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Uxbridge
country: United Kingdom
facility: Novartis Investigative Site
state: London
city: Frimley
country: United Kingdom
facility: Novartis Investigative Site
state: Surrey
city: Belfast
country: United Kingdom
facility: Novartis Investigative Site
city: Bristol
country: United Kingdom
facility: Novartis Investigative Site
city: Guildford, Surrey
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
city: Sunderland
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Pawloff M, Bogunovic H, Gruber A, Michl M, Riedl S, Schmidt-Erfurth U. SYSTEMATIC CORRELATION OF CENTRAL SUBFIELD THICKNESS WITH RETINAL FLUID VOLUMES QUANTIFIED BY DEEP LEARNING IN THE MAJOR EXUDATIVE MACULAR DISEASES. Retina. 2022 May 1;42(5):831-841. doi: 10.1097/IAE.0000000000003385.
citation: Li E, Donati S, Lindsley KB, Krzystolik MG, Virgili G. Treatment regimens for administration of anti-vascular endothelial growth factor agents for neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2020 May 5;5(5):CD012208. doi: 10.1002/14651858.CD012208.pub2.
citation: Waldstein SM, Coulibaly L, Riedl S, Sadeghipour A, Gerendas BS, Schmidt-Erfurth UM. Effect of posterior vitreous detachment on treat-and-extend versus monthly ranibizumab for neovascular age-related macular degeneration. Br J Ophthalmol. 2020 Jul;104(7):899-903. doi: 10.1136/bjophthalmol-2019-314661. Epub 2019 Sep 28.