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

Age-related Macular Degeneration Clinical Trial

— TREND  

Official title:

A 12-month, Phase IIIb, 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 AMD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01948830
• Other study ID #: CRFB002A2411
• Secondary ID: 2013-002626-23
• Status: Completed
• Phase: Phase 3
• First received: September 19, 2013
• Last updated: August 3, 2016
• Start date: December 2013
• Est. completion date: November 2015

Study information

• Verified date: August 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationBelgium: The Federal Public Service (FPS) Health, Food Chain Safety and EnvironmentSwitzerland: SwissmedicAustria: Federal Office for Safety in Health CareSpain: Ministry of HealthArgentina: Ministry of HealthBrazil: Ministry of HealthColombia: National Institutes of HealthCroatia: Ministry of Health and Social CareDenmark: Ministry of HealthEgypt: Ministry of Health and PopulationFinland: Ministry of Social Affairs and HealthGermany: Federal Institute for Drugs and Medical DevicesGuatemala: Ministry of Public Health and Social AssistanceHungary: Research Ethics Medical CommitteeIndia: Ministry of HealthIreland: Ministry of HealthSolomon Islands: National Health Research Ethics CommitteeIsrael: Ministry of HealthItaly: Ministry of HealthKorea: Food and Drug AdministrationLatvia: State Agency of MedicinesMexico: Ministry of HealthNetherlands: Medicines Evaluation Board (MEB)Netherlands: Ministry of Health, Welfare and SportNorway: Norwegian Medicines AgencyPoland: Ministry of HealthPortugal: National Pharmacy and Medicines InstituteRomania: National Authority for Scientific ResearchRussia: Ministry of Health of the Russian FederationSerbia and Montenegro: Agency for Drugs and Medicinal DevicesSlovakia: State Institute for Drug ControlSlovenia: Ministry of HealthSouth Africa: Department of HealthSweden: The National Board of Health and WelfareTurkey: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

This study is 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

Description:

This is 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 649
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Age-related Macular Degeneration
• Choroidal Neovascularization
• Macular Degeneration
• Neovascularization, Pathologic

Intervention

Drug:
• Ranibizumab 0.5mg
0.5 mg ranibizumab (intravitreal injections)
• Ranibizumab 0.5mg
0.5 mg ranibizumab (intravitreal injections)

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Antwerpen
Belgium	Novartis Investigative Site	Ottignies
Belgium	Novartis Investigative Site	Zottegem
Chile	Novartis Investigative Site	Santiago
Croatia	Novartis Investigative Site	Zagreb
Denmark	Novartis Investigative Site	Glostrup
Denmark	Novartis Investigative Site	Roskilde
Egypt	Novartis Investigative Site	Cairo	Abbassia
Egypt	Novartis Investigative Site	Cairo
Germany	Novartis Investigative Site	Ahaus
Germany	Novartis Investigative Site	Augsburg
Germany	Novartis Investigative Site	Chemnitz
Germany	Novartis Investigative Site	Darmstadt
Germany	Novartis Investigative Site	Göttingen
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Karlsruhe
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Ludwigshafen
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Siegburg
Germany	Novartis Investigative Site	Stuttgart
Germany	Novartis Investigative Site	Sulzbach
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	Budapest
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Pécs
Hungary	Novartis Investigative Site	Szeged
Hungary	Novartis Investigative Site	Zalaegerszeg
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Chennai	Tamil Nadu
India	Novartis Investigative Site	Vanchiyoor	Thiruvanantapuram
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Petach Tikva
Israel	Novartis Investigative Site	Rehovot
Israel	Novartis Investigative Site	Tel-Aviv
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Padova	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
Korea, Republic of	Novartis Investigative Site	Busan
Korea, Republic of	Novartis Investigative Site	Seongnam	Gyeonggi
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Portugal	Novartis Investigative Site	Coimbra
Portugal	Novartis Investigative Site	Coimbra
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Porto
Portugal	Novartis Investigative Site	Vila Franca de Xira
Russian Federation	Novartis Investigative Site	Kazan
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Novosibirsk
Russian Federation	Novartis Investigative Site	Samara
Slovakia	Novartis Investigative Site	Banska Bystrica
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Nove Zamky
Slovakia	Novartis Investigative Site	Poprad
Slovakia	Novartis Investigative Site	Zilina
Slovenia	Novartis Investigative Site	Ljubljana
Spain	Novartis Investigative Site	Barcelona	Cataluña
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Oviedo	Asturias
Spain	Novartis Investigative Site	Sant Cugat	Catalunya
Spain	Novartis Investigative Site	Valladolid	Castilla y Leon
Spain	Novartis Investigative Site	Zaragoza
Switzerland	Novartis Investigative Site	Bern
Switzerland	Novartis Investigative Site	Bern
Switzerland	Novartis Investigative Site	Lausanne
Switzerland	Novartis Investigative Site	Zuerich
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Ankara
United Kingdom	Novartis Investigative Site	Belfast
United Kingdom	Novartis Investigative Site	Bristol
United Kingdom	Novartis Investigative Site	Frimley	Surrey
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	Novartis Investigative Site	Uxbridge	London

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Belgium,  Chile,  Croatia,  Denmark,  Egypt,  Germany,  Hungary,  India,  Israel,  Italy,  Korea, Republic of,  Portugal,  Russian Federation,  Slovakia,  Slovenia,  Spain,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	BCVA change; by measuring BCVA score at 4 meters distance using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts	To demonstrate that the ranibizumab Treat and Extend regimen is non-inferior to ranibizumab monthly regimen in patients with nAMD as assessed by the change in best corrected visual acuity (BCVA) from baseline to Month 12	12 months	No
Secondary	Change in BCVA score from baseline to month 12	To evaluate the change in BCVA from baseline over time up to Month 12 by measuring BCVA score at 4 meters distance using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts	Baseline to Month 12	No
Secondary	Number of visits scheduled	The number of visits scheduled according to the treat and extend regimen after treatment initiation	From Month1 to Month 11	No
Secondary	Percentage of patients with Best Corrected Visual Acuity (BCVA) improvements =1, =5, =10, =15, and =30 letters by visit	Evaluate the occurrence of BCVA improvements of =1, =5, =10, =15, and =30 letters from baseline, over time up to Month 12. Measurements taken at 4 meters distance using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts	12 Months	No
Secondary	Percentage of patients with Best Corrected Visual Acuity (BCVA) loss >=73 letters by visit	Evaluate the occurrence of absolute BCVA =73 letters (20/40 Snellen equivalent) over time up to Month 12.	12 Months	No
Secondary	Percentage of patients with Best Corrected Visual Acuity (BCVA) loss <5, <10, and <15 letters by visit	Evaluate the occurrence of BCVA losses of <5, <10 and <15 letters from baseline, over time up to Month 12	12 Months	No
Secondary	BCVA score measured at 4 meters distance using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts	Evaluate the time course of mean BCVA from baseline up to Month 12	12 Months	Yes
Secondary	Average change in BCVA from Baseliine to Month 12	BCVA score measured at 4 meters distance using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts	Baseline, 12 months	No
Secondary	Period (time) between injections	To assess treatment frequency and average dosing interval	12 Months	No
Secondary	Presence of the disease activity	To evaluate the occurrence of a fluid free macula (e.g., no intra-retinal and/or sub-retinal fluid as measured on spectral domain OCT (SD-OCT) over time up to Month 12	12 Months	No
Secondary	Change from baseline in central retinal thickness of the study eye over time	To evaluate the change in central subfield retinal thickness (CSFT) collected by SD-OCT, as evaluated by the Central Reading Center (CRC) from baseline, over time up to Month 12	12 Months	No
Secondary	Percentage of patients with Choroidal Neovascularization (CNV) leakage in the study eye	To evaluate presence of active CNV leakage on fluorescein angiography (FA) by reading center over time up to Month 12.	12 Months	No
Secondary	Quality of Life	To assess the impact on patient functioning and quality of life supported by ranibizumab 0.5 as assessed by the NEI-VFQ-25	12 Months	No
Secondary	Number of participants with Adverse Events as a measure of Safety and Tolerability		12 Months	Yes