Compare Safety/Efficacy of Labeled vs Wait-Extend Regimen of Lucentis in Turkish Patients With VI Due to DME (SALUTE-D)

Novartis

Status and phase: Completed; Phase 3

Conditions: Diabetic Macular Edema

Treatments: Drug: Wait and Extend regime arm; Drug: Labeled regime arm

Study type: Interventional

Funder types: Industry

Identifiers

NCT02262260

CRFB002DTR01

Details and patient eligibility

About

To explore a more clinical feasible treatment regime with ranibizumab for DME to provide satisfactory treatment effect with a lower number of visits and injections.

Full description

Diabetes mellitus (DM) is the most common endocrine disease in developed countries, with prevalence estimates ranging between 2 to 5% of the world's population. Diabetic retinopathy (DR) and diabetic macular edema (DME) are common microvascular complications in patients with diabetes and may have a sudden and debilitating impact on visual acuity (VA), eventually leading to blindness. DME is a frequent manifestation of DR and is the major cause of visual loss in patients with DR. If left untreated, >50% of patients lose >2 lines of visual acuity (VA) within 2 years. DME mostly affects the working-age population, imposing a significant burden both on society and on individual patients - a burden that is expected to increase with the rising prevalence of diabetes.

Enrollment: 87 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Written informed consent must be obtained before any assessment is performed.
• M or F patients >18 years of age who have signed an informed consent
• Patients with Type 1 or Type 2 DM (according to ADA or WHO guidelines) with HbA1c not more than 12.0% at screening (Visit 1). Patients should be on diet, exercise, and/or pharmacological treatment for diabetes.
• Patients with visual impairment due to focal or diffuse macular edema with center involvement in at least one eye, as demonstrated with color fundus photography, fluorescein angiography and OCT within 28 days of the baseline treatment. If both eyes are eligible, the one with the worse visual acuity, as assessed at Visit 1, will be selected for study treatment unless, based on medical reasons, the investigator deems the other eye the more appropriate candidate for study treatment. The study eye must fulfill the following criteria at Visit 1:
• BCVA score between 78 and 39 letters, inclusively, using ETDRS-like visual acuity testing charts at a testing distance of 4 meters (approximate Snellen equivalent of 20/32 to 20/160)
• Decrease in vision is due to DME and not due to other causes, in the opinion of the investigator

Exclusion Criteria

• Concomitant conditions in the study eye according to defined criteria such as infection, inflammation, uncontrolled glaucoma
• Active PDR in the study eye or evidence of vitreomacular traction in either eye
• Patients who are monocular or have a BCVA score in the non-study eye (fellow eye) £ 24 letters at Visit 1
• Concomitant systemic condition according to defined criteria, eg. history of stroke, uncontrolled diabetes, renal failure, unsatisfactory controlled hypertension
• Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days until the expected PD effect has returned to baseline, whichever is longer.
• History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment.

Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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87 participants in 2 patient groups

Ranibizumab labeled regime arm

Experimental group

Description:

Ranibizumab (Anti VEGF) 0.5mg treatment will be given monthly and will be continued until maximum visual acuity is achieved (the patient's visual acuity is stable for three consecutive monthly assessments performed while on ranibizumab treatment). Thereafter patients should be monitored monthly for visual acuity. Treatment will be resumed when monitoring indicates loss of visual acuity due to DME. Monthly injections should then be administered until stable visual acuity is reached again for three consecutive monthly assessments (implying a minimum of two injections). The interval between two doses should not be shorter than 1 month

Treatment:

Drug: Labeled regime arm

Ranibizumab wait and Extend regime arm

Experimental group

Description:

Ranibizumab (Anti VEGF) 0.5 mg will be injected subsequently at baseline, month 1 and 2. After the three initial loading doses, patients will be called for the control visits 1 month later. If the visual acuity has reached a stable level and there is no sign of edema on OCT, patients will not receive intravitreal injection and will be called to come back 6 weeks later. The interval is increased by 2 weeks until a maximum of 8 weeks as long as the patient presents as stable regarding visual acuity, central retinal thickness and clinical findings. If there is a negative change, the interval is shortened back to 4 weeks.

Treatment:

Drug: Wait and Extend regime arm