The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01535261




Registration number
NCT01535261
Ethics application status
Date submitted
14/02/2012
Date registered
17/02/2012
Date last updated
27/10/2016

Titles & IDs
Public title
Ranibizumab Intravitreal Injections in Patients With Visual Impairment Due to Macular Edema Secondary to Central Retinal Vein Occlusion
Scientific 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
Secondary ID [1] 0 0
2011-002350-31
Secondary ID [2] 0 0
CRFB002E2401
Universal Trial Number (UTN)
Trial acronym
CRYSTAL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Macular Edema 0 0
Central Retinal Vein Occlusion 0 0
Condition category
Condition code
Eye 0 0 0 0
Diseases / disorders of the eye
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ranibizumab 0.5 mg/0.05 ml

Experimental: Ranibizumab arm - Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN


Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean Change in Best Corrected Visual Acuity (BCVA) at Month 12 Compared to Baseline - Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. A positive average change from baseline of BCVA indicates improvement
Timepoint [1] 0 0
Baseline to month 12
Secondary outcome [1] 0 0
Mean Change in Best Corrected Visual Acuity (BCVA) at Month 24 Compared to Baseline - Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. A positive average change from baseline of BCVA indicates improvement
Timepoint [1] 0 0
Baseline to Month 24
Secondary outcome [2] 0 0
Mean Average Change in Best Corrected Visual Acuity (BCVA From Baseline Month 12 and Month 24 - Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. Mean Average Change: for each patient, first average change is calculated as the average of the changes from baseline to Month 1 over Month 12 (or Month 24). Then, mean average change is calculated as the average of average changes across all patients.
Timepoint [2] 0 0
Baseline and Month 1 to 12 or Month 24
Secondary outcome [3] 0 0
Mean Average Change in BCVA From First Treatment Interruption (Due to BCVA Stabilization) to Month 12 and Month 24 - Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. Stability in visual acuity after treatment interruption indicates longer duration of the drug efficacy
Timepoint [3] 0 0
Month 12 and Month 24
Secondary outcome [4] 0 0
Number 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 - BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An increased score indicates improvement in acuity. This outcome assessed the number of participants who had improvement of =1, =5, =10, =15, and =30 letters of visual acuity at month 12 as compared with baseline
Timepoint [4] 0 0
Month 12 and Month 24
Secondary outcome [5] 0 0
Number of Patients With a BCVA Value of = 73 Letters (Approximate 20/40 Snellen Chart Equivalent) at Month 12 and Month 24 - Best Corrected Visual Acuity (BCVA) was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart at baseline and month 12 while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. BCVA above 73 letters at month 12 and month 24 indicates a positive outcome.
Timepoint [5] 0 0
Month 12 and Month 24
Secondary outcome [6] 0 0
Mean Change in Central Reading Center (CRC)-Assessed Central Subfield Thickness (CSFT) From Month 12 and Month 24 Compared to Baseline - Retinal thickness was measured using Optical Coherence Tomography (OCT). The images were reviewed by a central reading center to ensure a standardized evaluation
Timepoint [6] 0 0
Baseline, Month 12 and Month 24
Secondary outcome [7] 0 0
Mean Change in Patient-reported Outcomes in NEI-VFQ-25 Composite and Subscale Scores 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. The score of each individual question ranges from 0 (worst) to 100 which indicates the best possible response. The composite score and score of each of each construct also range from 0 to 100 as they are calculated as total scores divided by the number of questions. The higher the values of total scores represent better outcome. Scores per visit and of the change descriptively by visit.
Timepoint [7] 0 0
Month 12 and Month 24

Eligibility
Key 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)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Parramatta
Recruitment hospital [2] 0 0
Novartis Investigative Site - Sydney
Recruitment hospital [3] 0 0
Novartis Investigative Site - Melbourne
Recruitment hospital [4] 0 0
Novartis Investigative Site - Nedlands
Recruitment postcode(s) [1] 0 0
2150 - Parramatta
Recruitment postcode(s) [2] 0 0
2000 - Sydney
Recruitment postcode(s) [3] 0 0
3002 - Melbourne
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Linz
Country [2] 0 0
Austria
State/province [2] 0 0
Wien
Country [3] 0 0
Canada
State/province [3] 0 0
Alberta
Country [4] 0 0
Canada
State/province [4] 0 0
British Columbia
Country [5] 0 0
Canada
State/province [5] 0 0
Ontario
Country [6] 0 0
Canada
State/province [6] 0 0
Quebec
Country [7] 0 0
Czech Republic
State/province [7] 0 0
Olomouc
Country [8] 0 0
Czech Republic
State/province [8] 0 0
Praha 10
Country [9] 0 0
Denmark
State/province [9] 0 0
Glostrup
Country [10] 0 0
Greece
State/province [10] 0 0
GR
Country [11] 0 0
Greece
State/province [11] 0 0
Patras
Country [12] 0 0
Greece
State/province [12] 0 0
Thessaloniki
Country [13] 0 0
Hungary
State/province [13] 0 0
Budapest
Country [14] 0 0
Hungary
State/province [14] 0 0
Debrecen
Country [15] 0 0
Ireland
State/province [15] 0 0
Dublin 7
Country [16] 0 0
Ireland
State/province [16] 0 0
Dublin
Country [17] 0 0
Italy
State/province [17] 0 0
BO
Country [18] 0 0
Italy
State/province [18] 0 0
FI
Country [19] 0 0
Italy
State/province [19] 0 0
MI
Country [20] 0 0
Italy
State/province [20] 0 0
RM
Country [21] 0 0
Italy
State/province [21] 0 0
TO
Country [22] 0 0
Italy
State/province [22] 0 0
Udine
Country [23] 0 0
Netherlands
State/province [23] 0 0
Amsterdam
Country [24] 0 0
Netherlands
State/province [24] 0 0
Leiden 2333 ZA
Country [25] 0 0
Netherlands
State/province [25] 0 0
Nijmegen
Country [26] 0 0
Netherlands
State/province [26] 0 0
Rotterdam
Country [27] 0 0
Netherlands
State/province [27] 0 0
Tilburg
Country [28] 0 0
Poland
State/province [28] 0 0
Bielsko-Biala
Country [29] 0 0
Poland
State/province [29] 0 0
Gdansk
Country [30] 0 0
Poland
State/province [30] 0 0
Kraków
Country [31] 0 0
Poland
State/province [31] 0 0
Lublin
Country [32] 0 0
Poland
State/province [32] 0 0
Warszawa
Country [33] 0 0
Poland
State/province [33] 0 0
Wroclaw
Country [34] 0 0
Portugal
State/province [34] 0 0
Coimbra
Country [35] 0 0
Portugal
State/province [35] 0 0
Lisboa
Country [36] 0 0
Portugal
State/province [36] 0 0
Porto
Country [37] 0 0
Slovakia
State/province [37] 0 0
Slovak Republic
Country [38] 0 0
Slovakia
State/province [38] 0 0
Banska Bystrica
Country [39] 0 0
Slovakia
State/province [39] 0 0
Bratislava
Country [40] 0 0
Spain
State/province [40] 0 0
Castilla y Leon
Country [41] 0 0
Spain
State/province [41] 0 0
Cataluña
Country [42] 0 0
Spain
State/province [42] 0 0
Comunidad Valenciana
Country [43] 0 0
Spain
State/province [43] 0 0
Galicia
Country [44] 0 0
Spain
State/province [44] 0 0
Pais Vasco
Country [45] 0 0
Sweden
State/province [45] 0 0
Örebro
Country [46] 0 0
Switzerland
State/province [46] 0 0
Bern
Country [47] 0 0
Switzerland
State/province [47] 0 0
Lausanne
Country [48] 0 0
Switzerland
State/province [48] 0 0
Zuerich
Country [49] 0 0
Turkey
State/province [49] 0 0
Ankara
Country [50] 0 0
United Kingdom
State/province [50] 0 0
Surrey
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Belfast
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Birmingham
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Bristol
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Hull
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Liverpool
Country [56] 0 0
United Kingdom
State/province [56] 0 0
London
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Newcastle upon Tyne
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Plymouth
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The present study provided 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 was analyzed to gain insights into predictive factors for
disease progression and the possibility of reduced monitoring was assessed in Year 2. The
results of this open-label study provided long-term safety and efficacy data to further guide
recommendations on the use of ranibizumab in this indication.
Trial website
https://clinicaltrials.gov/show/NCT01535261
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications