Ranibizumab Intravitreal Injections in Patients With Visual Impairment Due to Macular Edema Secondary to Central Retinal Vein Occlusion

Macular Edema Clinical Trial

— CRYSTAL  

Official title:

A 24-month, Phase IIIb, Open-label, Single Arm, Multicenter Study Assessing the Efficacy and Safety of an Individualized, Stabilization-criteria-driven PRN Dosing Regimen With 0.5-mg Ranibizumab Intravitreal Injections Applied as Monotherapy in Patients With Visual Impairment Due to Macular Edema Secondary to Central Retinal

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01535261
• Other study ID #: CRFB002E2401
• Secondary ID: 2011-002350-31
• Status: Completed
• Phase: Phase 3
• First received: February 14, 2012
• Last updated: March 7, 2016
• Start date: February 2012
• Est. completion date: March 2015

Study information

• Verified date: March 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAustria: Agency for Health and Food SafetyAustralia: Department of Health and Ageing Therapeutic Goods AdministrationCanada: Health CanadaCzech Republic: State Institute for Drug ControlDenmark: National Board of HealthFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesGreece: National Organization of MedicinesHungary: National Institute of PharmacyIreland: Irish Medicines BoardItaly: The Italian Medicines AgencyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsPortugal: National Pharmacy and Medicines InstituteSlovakia: State Institute for Drug ControlSpain: Agencia Española de Medicamentos y Productos SanitariosSwitzerland: SwissmedicSweden: The National Board of Health and WelfareTurkey: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

The present study will provide additional efficacy and safety data for 0.5-mg ranibizumab using as needed (PRN) dosing over 24 months in patients with visual impairment due to macular edema secondary to Central Retinal Vein Occlusion (CRVO). Spectral domain high-definition optical coherence tomography (OCT) images will be analyzed to gain insights into predictive factors for disease progression and the possibility of reduced monitoring will be assessed in Year 2. The results of this open-label study will provide long-term safety and efficacy data to further guide recommendations on the use of ranibizumab in this indication.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 357
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female patients = 18 years of age

• Diagnosis of visual impairment exclusively due to ME secondary to CRVO

• BCVA score at Screening and Baseline between 73 and 19 letters Early Treatment Diabetic Retinopathy Study (ETDRS), inclusively (approximate Snellen chart equivalent of 20/40 and 20/400)

Exclusion Criteria:

• Uncontrolled blood pressure defined as systolic value of > 160 mm Hg or diastolic value of > 100 mm Hg at Screening or Baseline.

• Any active periocular or ocular infection or inflammation at Screening or Baseline in either eye

• Uncontrolled glaucoma at Screening or Baseline or diagnosed within 6 months before Baseline in either eye

• Use of any systemic antivascular endothelial growth factor (anti-VEGF) drugs within 6 months before Baseline (eg, sorafenib [Nexavar®], sunitinib [Sutent®], bevacizumab [Avastin®])

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Central Retinal Vein Occlusion
• Edema
• Macular Edema
• Retinal Vein Occlusion

Intervention

Drug:
• Ranibizumab 0.5 mg/0.05 ml
Patients will receive the first dose at Baseline, as an intravitreal injection with a standard dose of 0.5 mg/0.05 ml. Patients will receive at least 3 study treatments at monthly intervals (Day 1, Month 1 and Month 2). The last mandatory dose during treatment initiation will be administered approximately 60 days after the first study treatment. If there is no improvement in VA over the course of the first 3 injections, continued treatment is not recommended and the patient may receive alternative treatment at the investigator's discretion.

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Melbourne	Victoria
Australia	Novartis Investigative Site	Nedlands	Western Australia
Australia	Novartis Investigative Site	Parramatta	New South Wales
Australia	Novartis Investigative Site	Sydney	New South Wales
Austria	Novartis Investigative Site	Linz
Austria	Novartis Investigative Site	Wien
Canada	Novartis Investigative Site	Boisbriand	Quebec
Canada	Novartis Investigative Site	Calgary	Alberta
Canada	Novartis Investigative Site	London	Ontario
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Vancouver	British Columbia
Canada	Novartis Investigative Site	Victoria	British Columbia
Czech Republic	Novartis Investigative Site	Olomouc
Czech Republic	Novartis Investigative Site	Praha 10
Denmark	Novartis Investigative Site	Glostrup
Greece	Novartis Investigative Site	Athens	GR
Greece	Novartis Investigative Site	Heraklion Crete	GR
Greece	Novartis Investigative Site	Larissa	GR
Greece	Novartis Investigative Site	Patras
Greece	Novartis Investigative Site	Thessaloniki
Greece	Novartis Investigative Site	Thessaloniki	GR
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
Ireland	Novartis Investigative Site	Dublin
Ireland	Novartis Investigative Site	Dublin 7
Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Torino	TO
Italy	Novartis Investigative Site	Udine
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Leiden 2333 ZA
Netherlands	Novartis Investigative Site	Nijmegen
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Tilburg
Poland	Novartis Investigative Site	Bielsko-Biala
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Kraków
Poland	Novartis Investigative Site	Lublin
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Wroclaw
Portugal	Novartis Investigative Site	Coimbra
Portugal	Novartis Investigative Site	Coimbra
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Porto
Portugal	Novartis Investigative Site	Porto
Slovakia	Novartis Investigative Site	Banska Bystrica
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Zilina	Slovak Republic
Spain	Novartis Investigative Site	Alicante	Comunidad Valenciana
Spain	Novartis Investigative Site	Barcelona	Cataluña
Spain	Novartis Investigative Site	Barcelona	Cataluña
Spain	Novartis Investigative Site	Bilbao	Pais Vasco
Spain	Novartis Investigative Site	L´Hospitalet de Llobregat	Cataluña
Spain	Novartis Investigative Site	Santiago de Compostela	Galicia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Valladolid	Castilla y Leon
Sweden	Novartis Investigative Site	Örebro
Switzerland	Novartis Investigative Site	Bern
Switzerland	Novartis Investigative Site	Lausanne
Switzerland	Novartis Investigative Site	Zuerich
Turkey	Novartis Investigative Site	Ankara
United Kingdom	Novartis Investigative Site	Belfast
United Kingdom	Novartis Investigative Site	Birmingham
United Kingdom	Novartis Investigative Site	Bristol
United Kingdom	Novartis Investigative Site	Frimley	Surrey
United Kingdom	Novartis Investigative Site	Hull
United Kingdom	Novartis Investigative Site	Liverpool
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Newcastle upon Tyne
United Kingdom	Novartis Investigative Site	Plymouth
United Kingdom	Novartis Investigative Site	Southampton

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Australia,  Austria,  Canada,  Czech Republic,  Denmark,  Greece,  Hungary,  Ireland,  Italy,  Netherlands,  Poland,  Portugal,  Slovakia,  Spain,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean change in BCVA at month 12 compared to baseline for evaluating the efficacy of an individualized stabilization criteria driven PRN dosing regimen	For the mean change of BCVA at Month 12 compare to Baseline, the 95% confidence interval and P value (related to the null hypothesis that this mean change is equal to zero) based on a t distribution/t test will be calculated	From baseline to month 12	No
Secondary	Mean change in BCVA from Month 1 through Month 24 compared to Baseline	Will be assessed as per the primary efficacy endpoint. Related to the number and proportion of patients with BCVA letter gain or loss from Baseline will be assessed by 95% confidence intervals and P values based on the binomial distribution or exact binomial test.	From baseline and followed up Month 24	No
Secondary	Mean change in BCVA from Month the time point of the first treatment interruption (due to BCVA stabilization) through Month 24 by visit	Will be assessed as per the primary efficacy endpoint. Related to the number and proportion of patients with BCVA letter gain or loss from Baseline will be assessed by 95% confidence intervals and P values based on the binomial distribution or exact binomial test.	First treatment interruption through month 24	No
Secondary	Mean average change in BCVA from Month 1 through Month 12 and from Month 1 through Month 24 compared to Baseline	Will be assessed as per the primary efficacy endpoint. Related to the number and proportion of patients with BCVA letter gain or loss from Baseline will be assessed by 95% confidence intervals and P values based on the binomial distribution or exact binomial test.	From Month 1 and followed up month 24	No
Secondary	Mean average change in BCVA from the time point of the first treatment interruption (due to BCVA stabilization) through Month 12 and/or Month 24	Will be assessed as per the primary efficacy endpoint. Related to the number and proportion of patients with BCVA letter gain or loss from Baseline will be assessed by 95% confidence intervals and P values based on the binomial distribution or exact binomial test.	From Month 1 and followed up Month 24	No
Secondary	Number and proportion of patients with a BCVA value of = 73 letters (approximate 20/40 Snellen chart equivalent) at Month 12 and Month 24	Will be assessed as per the primary efficacy endpoint. Related to the number and proportion of patients with BCVA letter gain or loss from Baseline will be assessed by 95% confidence intervals and P values based on the binomial distribution or exact binomial test.	Month 12 and Month 24	No
Secondary	Number and proportion of patients with a BCVA value of < 15 letters from Baseline up to Month 12 and Month 24	Will be assessed as per the primary efficacy endpoint. Related to the number and proportion of patients with BCVA letter gain or loss from Baseline will be assessed by 95% confidence intervals and P values based on the binomial distribution or exact binomial test.	Month 12 and Month 24	No
Secondary	Mean change in CRC-assessed CSFT from Month 1 through Month 12 and Month 24 compared to Baseline	Will be assessed as per the primary efficacy endpoint. Related to the number and proportion of patients with BCVA letter gain or loss from Baseline will be assessed by 95% confidence intervals and P values based on the binomial distribution or exact binomial test.	Baseline through Month 24	No
Secondary	Mean change in patient-reported outcomes in NEI-VFQ-25 score (compared score and subscales) at Month 12 and Month 24 compared to Baseline	The survey consists of 25 items representing 11 vision-related constructs (general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, peripheral vision) plus a single-item general health rating question. Scores per visit and of the change from Baseline for the composite score and subscales will be summarized descriptively by visit.	Month 12 and Month 24	No
Secondary	The number and proportion of patients with a BCVA improvement of =1, =5, =10, =15, and =30 letters from Baseline to Month 12 and Month 24 in the study eye, by visit	Will be assessed as per the primary efficacy endpoint. Related to the number and proportion of patients with BCVA letter gain from Baseline will be assessed by 95% confidence intervals and P values based on the binomial distribution or exact binomial test	Month 12 and Month 24	No