Oral Everolimus +/- Lucentis, in patients with neovascular AMD v1

• Research type

  Research Study

• Full title

  A randomized, double-masked, parallel group study to assess the efficacy of oral Everolimus 5mg q.d., either alone or added to Lucentis, in patients with neovascular age-related macular degeneration

• Sponsor organisation

  Novartis Pharma Services AG

• Eudract number

  2008-003550-15

• ISRCTN Number

  N/A

• Clinicaltrials.gov Identifier

  N/A

• Research summary

  Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world and is characterised by degeneration of the central part of the retina (macula). AMD is classified into two types: non neovascular AMD (Dry) and neovascular AMD (wet). It is estimated that approximately 245,000 people in the UK have the neovascular form of AMD.The approved drug Lucentis (ranibizumab) is the current standard of care for AMD and requires up to monthly intravitreal injections. RAD001 (Everolimus) is approved and commercialized (as Certican©) in over 60 countries to prevent organ rejection after kidney or heart transplants. RAD001 inhibits a protein called mTOR and it has antimicrobial, anti-inflammatory and immunosuppressive activities.It is likely that other growth factors and the immune system in the eye are involved in the progression of AMD. There is extensive preclinical evidence that inhibition of the mTOR pathway, using RAD001 at doses comparable to those used in this trial, decreases leakage in the retinal vasculature and reduces retinal vascular proliferation. Further more in a preclinical setting RAD001 had an additive effect with a VEGF receptor 2 inhibitor, suggesting that the drug could increase the response to a VEGF inhibitor such as Lucentis. The efficacy of RAD001 in the treatment of neovascular AMD in humans is unknown and is the objective of this study.For this 4 week proof of concept trial, there should be a low risk of adverse effects of RAD001. Because of the potential immunosuppressive effects of RAD001, a positive proof of concept will be followed by plans to develop a local ocular formulation for the long term treatment of neovascular AMD.

• REC name

  South Central - Oxford B Research Ethics Committee

• REC reference

  08/H0605/139

• Date of REC Opinion

  10 Dec 2008

• REC opinion

  Further Information Favourable Opinion