Randomized Study for Efficacy and Safety of Ranibizumab 0.5mg in Treat-extend and Monthly Regimens in Patients With nAMD

NCT ID: NCT01948830

Last Updated: 2017-04-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 650 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-17
• Study Completion Date: 2015-11-19

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.

Conditions

Age-related Macular Degeneration; Choroidal Neovascularization

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: SINGLE

Study Groups

Group I ranibizumab 0.5 mg monthly

Ranibizumab 0.5 mg/0.05 mL (Monthly regimen) up to month 11

Group Type: ACTIVE_COMPARATOR

Ranibizumab 0.5mg

Intervention Type: DRUG

0.5 mg ranibizumab (intravitreal injections) prefilled syringe)

Group II ranibizumab 0.5 mg TER

Ranibizumab 0.5 mg/0.05 mL (TER) treat and Extend regimen up to month 11

Group Type: ACTIVE_COMPARATOR

Ranibizumab 0.5mg

Intervention Type: DRUG

0.5 mg ranibizumab (intravitreal injections) prefilled syringe)

Interventions

Ranibizumab 0.5mg

0.5 mg ranibizumab (intravitreal injections) prefilled syringe)

Intervention Type: DRUG

Ranibizumab 0.5mg

0.5 mg ranibizumab (intravitreal injections) prefilled syringe)

Intervention Type: DRUG

Other Intervention Names

Lucentis; Lucentis

Eligibility Criteria

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)

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.

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Antwerp, , Belgium

Novartis Investigative Site

Ottignies, , Belgium

Novartis Investigative Site

Zottegem, , Belgium

Novartis Investigative Site

Santiago, , Chile

Novartis Investigative Site

Zagreb, Croatia, Croatia

Novartis Investigative Site

Glostrup Municipality, , Denmark

Novartis Investigative Site

Roskilde, , Denmark

Novartis Investigative Site

Cairo, Abbassia, Egypt

Novartis Investigative Site

Cairo, , Egypt

Novartis Investigative Site

Leipzig, Germany, Germany

Novartis Investigative Site

Ahaus, , Germany

Novartis Investigative Site

Augsburg, , Germany

Novartis Investigative Site

Chemnitz, , Germany

Novartis Investigative Site

Cologne, , Germany

Novartis Investigative Site

Darmstadt, , Germany

Novartis Investigative Site

Göttingen, , Germany

Novartis Investigative Site

Hanover, , Germany

Novartis Investigative Site

Karlsruhe, , Germany

Novartis Investigative Site

Ludwigshafen, , Germany

Novartis Investigative Site

Magdeburg, , Germany

Novartis Investigative Site

Münster, , Germany

Novartis Investigative Site

Münster, , Germany

Novartis Investigative Site

Siegburg, , Germany

Novartis Investigative Site

Stuttgart, , Germany

Novartis Investigative Site

Sulzbach, , Germany

Novartis Investigative Site

Budapest, , Hungary

Novartis Investigative Site

Budapest, , Hungary

Novartis Investigative Site

Budapest, , Hungary

Novartis Investigative Site

Budapest, , Hungary

Novartis Investigative Site

Budapest, , Hungary

Novartis Investigative Site

Budapest, , Hungary

Novartis Investigative Site

Debrecen, , Hungary

Novartis Investigative Site

Pécs, , Hungary

Novartis Investigative Site

Szeged, , Hungary

Novartis Investigative Site

Zalaegerszeg, , Hungary

Novartis Investigative Site

Bangalore, Karnataka, India

Novartis Investigative Site

Chennai, Tamil Nadu, India

Novartis Investigative Site

Vanchiyoor, Thiruvanantapuram, India

Novartis Investigative Site

Haifa, , Israel

Novartis Investigative Site

Jerusalem, , Israel

Novartis Investigative Site

Petah Tikva, , Israel

Novartis Investigative Site

Rehovot, , Israel

Novartis Investigative Site

Tel Aviv, , Israel

Novartis Investigative Site

Florence, FI, Italy

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Padua, PD, Italy

Novartis Investigative Site

Pisa, PI, Italy

Novartis Investigative Site

Roma, RM, Italy

Novartis Investigative Site

Sassari, SS, Italy

Novartis Investigative Site

Udine, UD, Italy

Novartis Investigative Site

Coimbra, Portugal, Portugal

Novartis Investigative Site

Coimbra, Portugal, Portugal

Novartis Investigative Site

Lisbon, Portugal, Portugal

Novartis Investigative Site

Porto, Portugal, Portugal

Novartis Investigative Site

Vila Franca de Xira, Portugal, Portugal

Novartis Investigative Site

Kazan', , Russia

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Novosibirsk, , Russia

Novartis Investigative Site

Samara, , Russia

Novartis Investigative Site

Banská Bystrica, Slovakia, Slovakia

Novartis Investigative Site

Nové Zámky, Slovakia, Slovakia

Novartis Investigative Site

Poprad, Slovakia, Slovakia

Novartis Investigative Site

Žilina, Slovakia, Slovakia

Novartis Investigative Site

Bratislava, , Slovakia

Novartis Investigative Site

Ljubljana, Slovenia, Slovenia

Novartis Investigative Site

Busan, Busan, South Korea

Novartis Investigative Site

Seongnam-si, Gyeonggi-do, South Korea

Novartis Investigative Site

Seoul, Korea, South Korea

Novartis Investigative Site

Seoul, Korea, South Korea

Novartis Investigative Site

Barcelona, Barcelona, Spain

Novartis Investigative Site

Valladolid, Castille and León, Spain

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Sant Cugat del Vallès, Catalonia, Spain

Novartis Investigative Site

Oviedo, Principality of Asturias, Spain

Novartis Investigative Site

Zaragoza, Zaragoza, Spain

Novartis Investigative Site

Bern, , Switzerland

Novartis Investigative Site

Bern, , Switzerland

Novartis Investigative Site

Lausanne, , Switzerland

Novartis Investigative Site

Zurich, , Switzerland

Novartis Investigative Site

Ankara, Turkey, Turkey (Türkiye)

Novartis Investigative Site

Ankara, , Turkey (Türkiye)

Novartis Investigative Site

Uxbridge, London, United Kingdom

Novartis Investigative Site

Frimley, Surrey, United Kingdom

Novartis Investigative Site

Belfast, , United Kingdom

Novartis Investigative Site

Bristol, , United Kingdom

Novartis Investigative Site

Guildford, Surrey, , United Kingdom

Novartis Investigative Site

London, , United Kingdom

Novartis Investigative Site

Manchester, , United Kingdom

Novartis Investigative Site

Sunderland, , United Kingdom

Countries

Belgium; Chile; Croatia; Denmark; Egypt; Germany; Hungary; India; Israel; Italy; Portugal; Russia; Slovakia; Slovenia; South Korea; Spain; Switzerland; Turkey (Türkiye); United Kingdom

References

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.

Reference Type: DERIVED

PMID: 34934034 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32374423 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31563866 (View on PubMed)

Other Identifiers

2013-002626-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CRFB002A2411

Identifier Type: -

Identifier Source: org_study_id