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

Novartis

Status and phase: Completed; Phase 4

Conditions: Retinal Vein Occlusion

Treatments: Biological: RFB002; Drug: Dexamethasone

Study type: Interventional

Funder types: Industry

Identifiers

NCT01580020

2011-005045-13 (EudraCT Number)

CRFB002EDE20

Details and patient eligibility

About

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).

Enrollment: 175 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

• 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)
      • Injectable 3-month depot progestins (PI=0.3-1.4; 0.88 corr.)
      • Intra-uterine progestin device (Mirena®, PI=0.16)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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175 participants in 2 patient groups

Ranibizumab (Arm A)

Experimental group

Description:

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

Treatment:

Biological: RFB002

Dexamethasone (Arm B)

Sham Comparator group

Description:

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.

Treatment:

Drug: Dexamethasone