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

NCT01535261 | Completed Phase 3 Results

• 2 other identifiers: CRFB002E24012011-002350-31
• Study Type: interventional
• Target: 357
• Locations: 17 countries
• Sites: 74

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.

Conditions

Macular Edema; Central Retinal Vein Occlusion

Keywords

Ophthalmology; Ranibizumab; Central Retinal Vein Occlusion

Outcome Measures

Primary Outcomes (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

  Baseline to month 12

Secondary Outcomes (7)

• Mean Change in Best Corrected Visual Acuity (BCVA) at Month 24 Compared to Baseline

  Baseline to Month 24

• Mean Average Change in Best Corrected Visual Acuity (BCVA From Baseline Month 12 and Month 24

  Baseline and Month 1 to 12 or Month 24

• Mean Average Change in BCVA From First Treatment Interruption (Due to BCVA Stabilization) to Month 12 and Month 24

  Month 12 and Month 24

• 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

  Month 12 and Month 24

• Number of Patients With a BCVA Value of ≥ 73 Letters (Approximate 20/40 Snellen Chart Equivalent) at Month 12 and Month 24

  Month 12 and Month 24

Study Arms (1)

Ranibizumab arm

EXPERIMENTAL

Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN

Drug: Ranibizumab 0.5 mg/0.05 ml

Interventions

Ranibizumab 0.5 mg/0.05 ml DRUG

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.

Ranibizumab arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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 \[Avastin®\])

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (78)

Novartis Investigative Site

Parramatta, New South Wales, 2150, Australia

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Novartis Investigative Site

Sydney, New South Wales, 2000, Australia

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Melbourne, Victoria, 3002, Australia

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Novartis Investigative Site

Nedlands, Western Australia, 6009, Australia

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Novartis Investigative Site

Vienna, Austria, 1090, Austria

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Novartis Investigative Site

Linz, 4021, Austria

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Novartis Investigative Site

Calgary, Alberta, T2H0C8, Canada

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Vancouver, British Columbia, V5Z 1M9, Canada

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Victoria, British Columbia, V8V 4X3, Canada

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London, Ontario, N6A 4G5, Canada

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Boisbriand, Quebec, J7H 1S6, Canada

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Montreal, Quebec, H1T 2M4, Canada

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Novartis Investigative Site

Olomouc, 775 20, Czechia

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Prague, 100 34, Czechia

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Glostrup Municipality, DK-2600, Denmark

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Pátrai, Greece, 26504, Greece

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Thessaloniki, Greece, GR 54636, Greece

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Athens, GR, 124 62, Greece

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Heraklion Crete, GR, 711 10, Greece

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Larissa, GR, 411 10, Greece

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Thessaloniki, GR, 546 29, Greece

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Budapest, 1133, Hungary

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Budapest, H-1083, Hungary

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Debrecen, 4032, Hungary

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Dublin, Ireland, Ireland

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Dublin, Ireland

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Bologna, BO, 40138, Italy

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Florence, FI, 50134, Italy

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Milan, MI, 20100, Italy

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Milan, MI, 20132, Italy

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Roma, RM, 00144, Italy

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Torino, TO, 10122, Italy

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Udine, 33100, Italy

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Novartis Investigative Site

Leiden 2333 ZA, Netherlands, 2333, Netherlands

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Amsterdam, 1081, Netherlands

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Nijmegen, 6525 GA, Netherlands

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Rotterdam, 3011 BH, Netherlands

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Tilburg, 5022 GC, Netherlands

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Novartis Investigative Site

Bielsko-Biala, 43-300, Poland

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Gdansk, 80-809, Poland

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Novartis Investigative Site

Krakow, 31-501, Poland

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Lublin, 20-079, Poland

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Novartis Investigative Site

Warsaw, 02-005, Poland

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Wroclaw, 50-556, Poland

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Novartis Investigative Site

Porto, Porto District, 4200-319, Portugal

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Novartis Investigative Site

Coimbra, Portugal, 3000-354, Portugal

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Novartis Investigative Site

Coimbra, Portugal, 3030-163, Portugal

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Novartis Investigative Site

Porto, Portugal, 4099-001, Portugal

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Novartis Investigative Site

Lisbon, 1050-085, Portugal

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Novartis Investigative Site

Lisbon, 1349-019, Portugal

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Novartis Investigative Site

Žilina, Slovak Republic, 010 01, Slovakia

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Novartis Investigative Site

Bratislava, Slovakia, 826 06, Slovakia

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Novartis Investigative Site

Banská Bystrica, 975 17, Slovakia

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Novartis Investigative Site

Bilbao, Basque Country, 48006, Spain

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Novartis Investigative Site

Valladolid, Castille and León, 47011, Spain

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Novartis Investigative Site

Barcelona, Catalonia, 08022, Spain

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Novartis Investigative Site

Barcelona, Catalonia, Spain

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Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

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Novartis Investigative Site

Santiago de Compostela, Galicia, 15706, Spain

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Novartis Investigative Site

Alicante, Valencia, 03016, Spain

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Novartis Investigative Site

Valencia, Valencia, 46014, Spain

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Valencia, Valencia, 46015, Spain

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Novartis Investigative Site

Örebro, 701 85, Sweden

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Zurich, Switzerland, 8063, Switzerland

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Bern, 3012, Switzerland

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Novartis Investigative Site

Lausanne, 1007, Switzerland

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Novartis Investigative Site

Ankara, Turkey, 06100, Turkey (Türkiye)

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Novartis Investigative Site

Frimley, Surrey, GU16 7UJ, United Kingdom

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Novartis Investigative Site

London, United Kingdom, EC1V 2PD, United Kingdom

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Novartis Investigative Site

Belfast, BT12 6BA, United Kingdom

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Birmingham, B9 5SS, United Kingdom

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Novartis Investigative Site

Bristol, BS1 2LX, United Kingdom

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Novartis Investigative Site

Hull, HU3 2JZ, United Kingdom

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Liverpool, L69 3GA, United Kingdom

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London, NW1 5QH, United Kingdom

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Newcastle upon Tyne, NE1 4LP, United Kingdom

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Plymouth, PL4 6PL, United Kingdom

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Novartis Investigative Site

Southampton, SO16 6YD, United Kingdom

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Related Publications (2)

• 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.

  PMID: 34934034 DERIVED

• 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.

  PMID: 31047340 DERIVED

MeSH Terms

Conditions

Macular Edema; Retinal Vein Occlusion

Interventions

Ranibizumab

Condition Hierarchy (Ancestors)

Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases; Venous Thrombosis; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Novartis

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2012
• First Posted: February 17, 2012
• Study Start: February 1, 2012
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: October 27, 2016
• Results First Posted: June 3, 2016

Record last verified: 2016-09

Locations

SL (3); IT (7); AU (2); SE (1); CA (6); HU (3); DK (1); TU (1); ES (9); IE (2); GR (6); PT (6); CZ (2); GB (11); CH (3); PL (6); NL (5)