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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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
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
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
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
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
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
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
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
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
Sex
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
Not applicable
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
1/02/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/03/2015
Sample size
Target
Accrual to date
Final
357
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/study/NCT01535261
Trial related presentations / publications
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.
Larsen M, Waldstein SM, Priglinger S, Hykin P, Barnes E, Gekkieva M, Das Gupta A, Wenzel A, Mones J; CRYSTAL Study Group. Sustained Benefits from Ranibizumab for Central Retinal Vein Occlusion with Macular Edema: 24-Month Results of the CRYSTAL Study. Ophthalmol Retina. 2018 Feb;2(2):134-142. doi: 10.1016/j.oret.2017.05.016. Epub 2017 Sep 9.
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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01535261