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Macular EdemaPhase 3CRYSTALNCT01535261

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

A Phase 3 study testing Ranibizumab 0.5 mg/0.05 ml in people with Macular Edema and Central Retinal Vein Occlusion, run by Novartis Pharmaceuticals at 78 sites in 18 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Macular Edema, Central Retinal Vein Occlusion
What is being tested?
Ranibizumab 0.5 mg/0.05 ml
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
357 participants
Where
78 sitesin 18 countries
Study dates
Feb 2012to Mar 2015
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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®])

Trial locations and contacts

78 sites in 18 countries.

78 sites in 18 countries

United Kingdom11 sites

  • Novartis Investigative Site

    Belfast, BT12 6BA

  • Novartis Investigative Site

    Birmingham, B9 5SS

  • Novartis Investigative Site

    Bristol, BS1 2LX

  • Novartis Investigative Site

    Frimley, Surrey, GU16 7UJ

  • Novartis Investigative Site

    Hull, HU3 2JZ

  • Novartis Investigative Site

    Liverpool, L69 3GA

  • Novartis Investigative Site

    London, United Kingdom, EC1V 2PD

  • Novartis Investigative Site

    London, NW1 5QH

  • Novartis Investigative Site

    Newcastle upon Tyne, NE1 4LP

  • Novartis Investigative Site

    Plymouth, PL4 6PL

  • Novartis Investigative Site

    Southampton, SO16 6YD

Other trials in United Kingdom

Spain9 sites

  • Novartis Investigative Site

    Alicante, Valencia, 03016

  • Novartis Investigative Site

    Barcelona, Catalonia, 08022

  • Novartis Investigative Site

    Barcelona, Catalonia

  • Novartis Investigative Site

    Bilbao, Basque Country, 48006

  • Novartis Investigative Site

    L'Hospitalet de Llobregat, Catalonia, 08907

  • Novartis Investigative Site

    Santiago de Compostela, Galicia, 15706

  • Novartis Investigative Site

    Valencia, Valencia, 46014

  • Novartis Investigative Site

    Valencia, Valencia, 46015

  • Novartis Investigative Site

    Valladolid, Castille and León, 47011

Other trials in Spain

Italy7 sites

  • Novartis Investigative Site

    Bologna, BO, 40138

  • Novartis Investigative Site

    Florence, FI, 50134

  • Novartis Investigative Site

    Milan, MI, 20100

  • Novartis Investigative Site

    Milan, MI, 20132

  • Novartis Investigative Site

    Roma, RM, 00144

  • Novartis Investigative Site

    Torino, TO, 10122

  • Novartis Investigative Site

    Udine, 33100

Other trials in Italy

Canada6 sites

  • Novartis Investigative Site

    Boisbriand, Quebec, J7H 1S6

  • Novartis Investigative Site

    Calgary, Alberta, T2H0C8

  • Novartis Investigative Site

    London, Ontario, N6A 4G5

  • Novartis Investigative Site

    Montreal, Quebec, H1T 2M4

  • Novartis Investigative Site

    Vancouver, British Columbia, V5Z 1M9

  • Novartis Investigative Site

    Victoria, British Columbia, V8V 4X3

Other trials in Canada

Greece6 sites

  • Novartis Investigative Site

    Athens, GR, 124 62

  • Novartis Investigative Site

    Heraklion Crete, GR, 711 10

  • Novartis Investigative Site

    Larissa, GR, 411 10

  • Novartis Investigative Site

    Pátrai, Greece, 26504

  • Novartis Investigative Site

    Thessaloniki, Greece, GR 54636

  • Novartis Investigative Site

    Thessaloniki, GR, 546 29

Other trials in Greece

Poland6 sites

  • Novartis Investigative Site

    Bielsko-Biala, 43-300

  • Novartis Investigative Site

    Gdansk, 80-809

  • Novartis Investigative Site

    Krakow, 31-501

  • Novartis Investigative Site

    Lublin, 20-079

  • Novartis Investigative Site

    Warsaw, 02-005

  • Novartis Investigative Site

    Wroclaw, 50-556

Other trials in Poland

Portugal6 sites

  • Novartis Investigative Site

    Coimbra, Portugal, 3000-354

  • Novartis Investigative Site

    Coimbra, Portugal, 3030-163

  • Novartis Investigative Site

    Lisbon, 1050-085

  • Novartis Investigative Site

    Lisbon, 1349-019

  • Novartis Investigative Site

    Porto, Porto District, 4200-319

  • Novartis Investigative Site

    Porto, Portugal, 4099-001

Other trials in Portugal

Netherlands5 sites

  • Novartis Investigative Site

    Amsterdam, 1081

  • Novartis Investigative Site

    Leiden 2333 ZA, Netherlands, 2333

  • Novartis Investigative Site

    Nijmegen, 6525 GA

  • Novartis Investigative Site

    Rotterdam, 3011 BH

  • Novartis Investigative Site

    Tilburg, 5022 GC

Other trials in Netherlands

Australia4 sites

  • Novartis Investigative Site

    Melbourne, Victoria, 3002

  • Novartis Investigative Site

    Nedlands, Western Australia, 6009

  • Novartis Investigative Site

    Parramatta, New South Wales, 2150

  • Novartis Investigative Site

    Sydney, New South Wales, 2000

Other trials in Australia

Hungary3 sites

  • Novartis Investigative Site

    Budapest, 1133

  • Novartis Investigative Site

    Budapest, H-1083

  • Novartis Investigative Site

    Debrecen, 4032

Other trials in Hungary

Slovakia3 sites

  • Novartis Investigative Site

    Banská Bystrica, 975 17

  • Novartis Investigative Site

    Bratislava, Slovakia, 826 06

  • Novartis Investigative Site

    Žilina, Slovak Republic, 010 01

Other trials in Slovakia

Switzerland3 sites

  • Novartis Investigative Site

    Bern, 3012

  • Novartis Investigative Site

    Lausanne, 1007

  • Novartis Investigative Site

    Zurich, Switzerland, 8063

Other trials in Switzerland

Austria2 sites

  • Novartis Investigative Site

    Linz, 4021

  • Novartis Investigative Site

    Vienna, Austria, 1090

Other trials in Austria

Czechia2 sites

  • Novartis Investigative Site

    Olomouc, 775 20

  • Novartis Investigative Site

    Prague, 100 34

Other trials in Czechia

Ireland2 sites

  • Novartis Investigative Site

    Dublin, Ireland

  • Novartis Investigative Site

    Dublin

Other trials in Ireland

Denmark1 site

  • Novartis Investigative Site

    Glostrup Municipality, DK-2600

Other trials in Denmark

Sweden1 site

  • Novartis Investigative Site

    Örebro, 701 85

Other trials in Sweden

Turkey (Türkiye)1 site

  • Novartis Investigative Site

    Ankara, Turkey, 06100

Other trials in Turkey (Türkiye)

About this study

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

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.

Being tested
Ranibizumab 0.5 mg/0.05 ml
Keywords
Ophthalmology, Ranibizumab, Central Retinal Vein Occlusion
Medical subject headings
Macular Edema, Retinal Vein Occlusion

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ranibizumab 0.5 mg/0.05 mlDrug

    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.

Study groups in NCT01535261
Study groupRoleWhat they receive
Ranibizumab armExperimentalIntravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Receives: Drug: Ranibizumab 0.5 mg/0.05 ml

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Baseline to month 12

Secondary outcomes (7)

  1. 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

    Measured: Baseline to Month 24

  2. 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.

    Measured: Baseline and Month 1 to 12 or Month 24

  3. 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

    Measured: Month 12 and Month 24

  4. 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

    Measured: Month 12 and Month 24

  5. 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.

    Measured: Month 12 and Month 24

  6. 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

    Measured: Baseline, Month 12 and Month 24

  7. 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.

    Measured: Month 12 and Month 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Feb 2012 (estimated)
  2. Study startFeb 2012
  3. Primary completionMar 2015
  4. Study completionMar 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
357 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01535261
Sponsor's protocol ID
CRFB002E2401
Other IDs
2011-002350-31
Acronym
CRYSTAL
Status last verified
Sep 2016
First submitted
14 Feb 2012
Last updated
27 Oct 2016

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.

    PubMed 34934034

  • 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.

    PubMed 31047340

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ranibizumab 0.5 mg/0.05 ml in people with Macular Edema and Central Retinal Vein Occlusion, run by Novartis Pharmaceuticals at 78 sites in 18 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 78 sites in United Kingdom, Spain, Italy, Canada, Greece and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Change in Best Corrected Visual Acuity (BCVA) at Month 12 Compared to Baseline (time frame: Baseline to month 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01535261, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2016.

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