Extension Study to Compare Long-term Efficacy and Safety of Ranibizumab Intravitreal Injections Versus Dexamethasone Intravitreal Implant in Patients With RVO

NCT01580020 | Completed Phase 4 Results

• 2 other identifiers: CRFB002EDE202011-005045-13
• Study Type: interventional
• Target: 175
• Locations: 1 country
• Sites: 37

Brief Summary

The study is intended to characterize the clinical benefit regarding safety and efficacy of a long term treatment with Lucentis in comparison with Ozurdex over an additional 6 months and a 3-month follow-up period, following the initial 6-month treatment in the respective core studies CRFB002EDE17 (NCT01396057) and CRFB002EDE18 (NCT01396083).

Conditions

Retinal Vein Occlusion

Keywords

Macular Degeneration; Macular Edema; Retinal Vein Occlusion; Choroidal Neovascularization; Signs and Symptoms; Retinal Degeneration; Retinal Diseases; Eye Diseases; Venous Thrombosis Sensation Disorders; Dexamethasone acetate; Dexamethasone; Dexamethasone 21-phosphate; BB 1101; Anti-Inflammatory Agents; Therapeutic Uses; Vision, Low; Signs; Vision Disorders

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events as a Measure of Safety and Tolerability

  The number of participants who experienced Adverse events, serious AE and death

  6 months

Secondary Outcomes (8)

• Raw Mean Best Corrected Visual Acuity (BCVA) by Treatment Group

  Baseline, 6 months and 12 months

• Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline

  12 month

• Change in Central Subfield Thickness (CSRT) From Baseline to Month 12

  Baseline , Month 12

• Change of Foveal Center Point Thickness (FCPT) From Baseline to Month 12

  Baseline, Month 12

• Change in Mean Visual Function Questionnaire (VFQ-25)

  Baseline, 12 months

Study Arms (2)

Ranibizumab (Arm A)

EXPERIMENTAL

The PRN injection scheme applied in the core study will also be followed during this extension study: Patients should be monitored monthly (starting at V1E) for VA and treatment is to be resumed when monitoring indicates loss of VA due to disease activity. Monthly injections should then be administered until stable VA is reached again for 3 consecutive monthly assessments (implying a minimum of 2 injections during stable VA). The interval between 2 doses should not be shorter than 1 month

Biological: RFB002

Dexamethasone (Arm B)

SHAM COMPARATOR

A PRN re-treatment scheme will be applied for the Ozurdex arm during this extension study, i.e. patients may receive an implant at V1E or later as needed: Patients should be monitored monthly and if there is a decline from stable VA stability due to macular edema patients will receive another intravitreal implant. (700 µg; long acting release (LAR)) given that in the opinion of the investigator the patient would benefit from the re-treatment. However, a minimum period of 5 months in between implantations is required.

Drug: Dexamethasone

Interventions

RFB002 BIOLOGICAL

0.5 mg/0.05 mL solution to be injected intravitreally. Ranibizumab was formulated as a sterile solution aseptically filled in a sterile glass vial. Each vial contained ranibizumab in an aqueous solution (pH 5.5) with histidine, trehalose and polysorbate 20.

Ranibizumab (Arm A)

Dexamethasone DRUG

Ozurdex (Dexamethasone): intravitreal implant as per commercial label (700 µg Dexamethasone; Dexamethasone was formulated as a rod shaped implant to be inserted into the eye by an applicator. The implant as well as the respective applicator were suitable for single use only. Dexamethasone had to be stored according to label instructions and it had to be kept in a secure locked facility

Dexamethasone (Arm B)

Eligibility Criteria

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

You may qualify if:

• Patients must have completed the core study assessments at month 6 of study CRFB002EDE17 or CRFB002EDE18, respectively

You may not qualify if:

• Patients who experienced an uncontrollable rise in IOP during the core study CRFB002EDE17 respectively CRFB002EDE18, i.e. IOP could not be decreased to a stable level of \< 25mmHg.
• Use of other investigational drugs
• Current use or likely need of systemic medications known to be toxic to the lens, retina or optic nerve
• History of hypersensitivity to Ranibizumab or Ozurdex or any component of the ranibizumab respectively Ozurdey formulation
• Any type of advanced, severe or unstable disease or its treatment, that could interfere with evaluations or put the patient at special risk
• Women
• who were pregnant or breast feeding (pregnancy defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (\>5 mIU/mL)
• who were menstruating and capable of becoming pregnant\* and not practicing a medically approved method of contraception (Pearl Index \<1\*\*)\*\*\* during and up to at least 4 weeks after the end of treatment. A negative pregnancy test (serum) for all women and for girls entering menarche was required with sufficient lead time before randomization
• definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels \>40 mIU/mL or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy
• examples of particularly reliable methods with Pearl Index (PI) \<1, according to guidelines of "Deutsche Gesellschaft für Gynäkologie und Geburtshilfe":
• Combination pill with estrogen and gestagen (no mini-pill, PI=0.1-0.9)
• Vaginal ring (NuvaRing®, PI=0.65 uncorr.; 0.4 corr.)
• Contraceptive patch (EVRA®, PI= 0.72 uncorr.; 0.9 corr.)
• Estrogen-free ovulation inhibitors (Cerazette®, PI=0.14)
• Progestin-containing contraceptives (Implanon®, PI=0-0.08)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (37)

Novartis Investigative Site

Leipzig, Germany, 04103, Germany

Location

Novartis Investigative Site

Regensburg, Germany, 93042, Germany

Location

Novartis Investigative Site

Augsburg, 85155, Germany

Location

Novartis Investigative Site

Bad Rothenfelde, 49214, Germany

Location

Novartis Investigative Site

Berlin, 10713, Germany

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Bonn, 53127, Germany

Location

Novartis Investigative Site

Bremen, 28209, Germany

Location

Novartis Investigative Site

Chemnitz, 09113, Germany

Location

Novartis Investigative Site

Cologne, 50935, Germany

Location

Novartis Investigative Site

Darmstadt, 64297, Germany

Location

Novartis Investigative Site

Dresden, 01307, Germany

Location

Novartis Investigative Site

Düsseldorf, 40212, Germany

Location

Novartis Investigative Site

Düsseldorf, 40225, Germany

Location

Novartis Investigative Site

Frankfurt, 60318, Germany

Location

Novartis Investigative Site

Freiburg I. Br, 79106, Germany

Location

Novartis Investigative Site

Glauchau, 08371, Germany

Location

Novartis Investigative Site

Göttingen, 37075, Germany

Location

Novartis Investigative Site

Halle, 06114, Germany

Location

Novartis Investigative Site

Hamburg, 20246, Germany

Location

Novartis Investigative Site

Ingolstadt, 85049, Germany

Location

Novartis Investigative Site

Karlsruhe, 76133, Germany

Location

Novartis Investigative Site

Karlsruhe, 76199, Germany

Location

Novartis Investigative Site

Ludwigshafen, 67063, Germany

Location

Novartis Investigative Site

Marburg, 35039, Germany

Location

Novartis Investigative Site

Minden, 32427, Germany

Location

Novartis Investigative Site

Mülheim, 45468, Germany

Location

Novartis Investigative Site

München, 80336, Germany

Location

Novartis Investigative Site

München, 81675, Germany

Location

Novartis Investigative Site

Münster, 48145, Germany

Location

Novartis Investigative Site

Münster, 48149, Germany

Location

Novartis Investigative Site

Recklinghausen, 45657, Germany

Location

Novartis Investigative Site

Sulzbach, 66280, Germany

Location

Novartis Investigative Site

Tübingen, 72076, Germany

Location

Novartis Investigative Site

Ulm, 89075, Germany

Location

Novartis Investigative Site

Wolfsburg, 38442, Germany

Location

Novartis Investigative Site

Würzburg, 97080, Germany

Location

MeSH Terms

Conditions

Retinal Vein Occlusion; Macular Degeneration; Macular Edema; Choroidal Neovascularization; Signs and Symptoms; Retinal Degeneration; Retinal Diseases; Eye Diseases; Vision, Low; Vision Disorders

Interventions

Dexamethasone

Condition Hierarchy (Ancestors)

Venous Thrombosis; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Choroid Diseases; Uveal Diseases; Neovascularization, Pathologic; Metaplasia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Eye Diseases, Hereditary; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

trialandresults.registries@novartis.com

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 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2012
• First Posted: April 18, 2012
• Study Start: May 1, 2012
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: May 17, 2016
• Results First Posted: May 17, 2016

Record last verified: 2016-04

Locations

DE (37)