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: 21 August 2017
• Main ID: EUCTR2010-019795-74-BE
• Date of registration: 05/07/2010
• 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: 18/10/2010
• 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: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: ranibizumab/laser photocoagulation
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

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 are only permitted if, in the opinion of the investigator, they 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:
Ocular medical history
7. 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.
12. History of retinal detachment, retinal tear or macular hole in the study eye.
Prior Ocular treatments
15. Any intraocular surgery in the study eye within 3 months prior to randomization.
16. History of vitrectomy in study eye regardless of time prior to randomization.
18. Panretinal laser photocoagulation in the study eye within 6 months prior to randomization.
19. Focal/grid laser photocoagulation in the study eye within 3 months prior to randomization.
20. Treatment with anti-angiogenic drugs in either eye (pegaptanib sodium, anecortave
acetate, bevacizumab, ranibizumab, VEGF-Trap, etc.) within 3 months prior to
randomization.
22. History of intravitreal corticosteroid treatment in phakic study eye.
23. Intravitreal corticosteroids in post-cataract surgery study eye (aphakic or pseudophakic,
without damaged posterior capsule) within 3 months prior to randomization.
24. Ocular conditions in the study eye that require chronic concomitant therapy with topical
ocular corticosteroids.
25. Intraocular implants except for lenses.
Systemic conditions or treatments
26. History of stroke within 6 months prior to enrollment.
28. Untreated diabetes mellitus.
31. Conditions that require chronic concomitant therapy with systemically administered corticosteroids.



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

Health Condition(s) or Problem(s) studied

Diabetic Macular Edema (DME)
MedDRA version: 12.1 Level: LLT Classification code 10057934 Term: Diabetic macular edema

Intervention(s)

Trade Name: Lucentis
Pharmaceutical Form: Solution for injection

Primary Outcome(s)

Main Objective: To demonstrate stepwise that the mean average change from baseline in 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 non-inferior to 0.5 mg ranibizumab alone given PRN in patients with visual impairment due to DME and – if successful in the first step – to superiority. 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 for analyses is Month 12. The analyses based on data up to Month 12 will be performed after all patients have completed the Month 12 visit (or left the study prematurely). Access to these results will be restricted. Analyses based on data up to Month 24 will be performed at the end of this study.
Further technical details will appear in the Statistical Analysis Plan, which will be finalized prior to un-blinding of the clinical trial database and database lock.

Secondary Objective: Main secondary objectives of the trial:

?? To investigate within the TE dosing concepts the impact of laser treatment on the number of retreatments up to Month 12 and Month 24. Interpretation of the corresponding results needs to be done under consideration of possible differences related to efficacy.
?? 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 at Month 12 and at Month 24, 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 subfield thickness (CSFT) 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 from baseline to Month 12, and up to Month 24.

Secondary ID(s)

CRFB002D2304