A 2 year randomized, single-masked, multicenter, controlled phase IIIb trial assessing the Efficacy and safety of 0.5 mg ranibizumab in two “treat and extend” treatment algorithms vs. 0.5 mg ranibizumab as needed in patients with macular edema and visual Impairment secondary to diabetes mellitus - RETAIN

• Register: EUCTR
• Last refreshed on: 20 May 2013
• Main ID: EUCTR2010-019795-74-PL
• Date of registration: 06/10/2010
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A 2 year randomized, single-masked, multicenter, controlled phase IIIb trial assessing the Efficacy and safety of 0.5 mg ranibizumab in two “treat and extend” treatment algorithms vs. 0.5 mg ranibizumab as needed in patients with macular edema and visual Impairment secondary to diabetes mellitus - RETAIN
• Scientific title: A 2 year randomized, single-masked, multicenter, controlled phase IIIb trial assessing the Efficacy and safety of 0.5 mg ranibizumab in two “treat and extend” treatment algorithms vs. 0.5 mg ranibizumab as needed in patients with macular edema and visual Impairment secondary to diabetes mellitus - RETAIN
• Date of first enrolment: 11/01/2011
• Target sample size: 345
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-019795-74
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: yes Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: ranibizumab/laser photocoagulation

Countries of recruitment

Belgium, Czech Republic, France, Greece, Hungary, Ireland, Italy, Poland, Portugal, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Patient
1. Male or female patients > 18 years of age who have signed an Informed Consent.

2. Patients with Type 1 or Type 2 diabetes mellitus (according to American Diabetes Association or World Health Organization [WHO] guidelines) with glycosylated hemoglobin (HbA1c) = 12.0% at screening (Visit 1). Patients should be on diet, exercise, and/or pharmacological treatment for diabetes. Treatment for diabetes must have been stable for at least 3 month.

Ocular
3. Patients with visual impairment due to DME in at least one eye who are eligible for laser treatment in the opinion of the investigator. If both eyes are eligible, the one with the worse visual acuity, as assessed at Visit 1, will be selected by the investigator as the study eye.

4. BCVA = 39 and . 78 letters in the study eye and, inclusively, using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters (approximate Snellen equivalent of 20/32 to 20/160) at screening.

5. Concomitant conditions in the study eye which, in the opinion of the investigator, do not prevent improvement of visual acuity on study treatment.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Structural damage within 0.5 disc diameter of the center of the macular in the study eye likely to preclude improvement in visual acuity following the resolution of macular edema, including atrophy of the retinal pigment epithelium, subretinal fibrosis, laser scar(s), epiretinal membrane involving fovea or organized hard
exudate plaques.

Prior Ocular treatments
2. Any intraocular surgery in the study eye within 3 months prior to randomization.

3. History of vitrectomy in study eye regardless of time prior to randomization.

4. Planned medical or surgical intervention during the 24-months study period.

5. Panretinal laser photocoagulation in the study eye within 6 months prior to randomization.

6. Focal/grid laser photocoagulation in the study eye within 3 months prior to randomization.

7. Treatment with anti-angiogenic drugs in the study eye (pegaptanib sodium, anecortave acetate, bevacizumab, ranibizumab, VEGF-Trap, etc.) within 3 months prior to randomization.

8. Use of other investigational drugs at the time of enrollment, or within 3 month or 5 half-lives from enrollment, whichever is longer.

9. History of intravitreal corticosteroid treatment in phakic study eye.

10. Intravitreal corticosteroids in post-cataract surgery study eye (aphakic or pseudophakic, without damaged posterior capsule) within 3 months prior to randomization.

11. Ocular conditions in the study eye that require chronic concomitant therapy with topical ocular or systemically administered corticosteroids.

Systemic conditions or treatments
12. History of stroke within 6 months prior to enrollment.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Diabetic Macular Edema (DME)
MedDRA version: 14.1 Level: LLT Classification code 10057934 Term: Diabetic macular edema System Organ Class: 100000004853

Intervention(s)

Trade Name: Lucentis
Product Name: Lucentis
Product Code: RFB002D
Pharmaceutical Form: Solution for injection
Other descriptive name: ranibizumab
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Main Objective: To demonstrate that the mean change from baseline in Best Corrected Visual Acuity (BCVA) over a 12 month treatment period obtained with either a 0.5 mg ranibizumab “Treat and Extend” (TE) dosing regimen with adjunctive laser, and/or with 0.5 mg ranibizumab TE dosing regimen alone is at least non-inferior to 0.5 mg ranibizumab alone given PRN in patients with visual impairment due to DME to cover a potential superiority claim. The condition for the interpretation of these results is the assessment of the extent to which the TE dosing regimens could be maintained during the study duration.

Primary end point(s): The primary endpoint will be the difference between the average level of BCVA (letters) over all monthly post-baseline assessments from Month 1 to Month 12 and the baseline level of BCVA. The last assessment collected prior to start of treatment will be considered the baseline value.

Secondary Objective: Main secondary objectives of the trial:

•To demonstrate a stabilizing effect of adjunctive laser reflected in a lower number of study visits scheduled for treatment between Months 12 and 24, comparing 0.5mg ranibizumab TE dosing regimen with adjunctive laser with 0.5mg ranibizumab TE dosing regimen alone.

•To investigate the efficacy of 0.5 mg ranibizumab TE dosing regimen with adjunctive laser, 0.5 mg ranibizumab TE dosing regimen alone and 0.5 mg ranibizumab alone given PRN on vision-related functioning and well-being assessed during a period of 12 months, as measured by the overall score assessed by the National Eye Institute (NEI) Visual Function Questionnaire-25 (VFQ-25) and EuroQol EQ-5D.

•To compare the changes in development of central retinal thickness and central subfield thickness of 0.5 mg ranibizumab TE dosing regimen with adjunctive laser, 0.5 mg ranibizumab TE dosing regimen alone and 0.5 mg ranibizumab alone given PRN over time.

Secondary ID(s)

CRFB002D2304

2010-019795-74-BE