Trial Termination

The present message aims at updating the medical research community about the STRONG project (European Consortium for the Study of a Topical Treatment of iCRVO to prevent Neovascular Glaucoma – the STRONG Study), a clinical trial supported in part by the European Commission, launched in October 2012 following its selection for funding by European experts.

The sponsor of the STRONG trial (Gene Signal SAS) has proposed a new ophthalmic emulsion – aganirsen – for the treatment of ischaemic central retinal vein occlusion (iCRVO), this in order to prevent neovascular glaucoma (NVG). Aganirsen inhibits the IRS-1 and VEGF production and, further on in the pathological process, the development of neovascularizations. The ophthalmic emulsion aims at reaching the back of the eye and reducing neovascularizations on the retina. The resulting randomized, placebo-controlled clinical trial planned to involve 333 patients in about 35 trial sites across Europe: it aimed at evaluating the safety and efficacy of aganirsen and evaluating correct doses for the treatment of iCRVO.

At project start, protocol assistance was sought from the EMA to ensure that the protocol complies with the European regulation about the Orphan Drug Designation (ODD) of aganirsen for the treatment of NVG. The EMA Protocol Assistance ended in May 2013, a lengthy process due to negative opinions on the prior applications. The trial protocol was adapted according to EMA recommendations and finalised in March 2014. The sponsor applied for the “Treatment of CRVO” (treatment of iCRVO to prevent NVG) to the EMA in January 2014. The COMP published a Positive Opinion on 11 Apr 2014 (ref.: EMA/COMP/189040/2014).

The consortium partners went through all the general preparative work to perform the clinical trial: it includes the selection of qualified clinical trial sites, the preparation of all essential study documents, the submission to ethics committees and competent authorities, the training of study personnel, the development of an electronic data capture system including the electronic case report forms, and manuals for the reading centers to standardize the image capture.

Parallel sub-studies were also launched independently from the main study. The reading centre CORIC, Cologne, has developed a computer based method for the evaluation and quantification of pathological iris neovascularizations. At University Medical Center Mainz, autoantibody level analyses in retinal vein occlusion patients compared to healthy subjects were initiated and a project regarding the prevalence and incidence of glaucoma in retinal vein occlusion patients have started and are planned to end in 2018.

The sponsor (Gene Signal SAS) however did face critical stability issues during the first year of the project when validating the initial formulation involved in the topical treatment. In agreement with the European Commission, a first amendment allowing for a new project end (March 31-st 2018) was decided: it also gave Gene Signal the lead of an extra investment, not covered by public funds, in view of developing an alternate stable emulsion and its manufacturing process. A successful outcome was reached in early 2017 which allowed Gene Signal to patent the innovative formulation.

The above technical successes were however not sufficient to convince the European Commission about a second time amendment to the Grant Agreement, which was required to complete the trial then planned to end in late 2020. The STRONG consortium has therefore accepted the proposal of the European Commission to terminate the project on March 31-st 2018.

We are truly sorry about this decision, despite all of our past efforts to prepare this critical trial which aimed at addressing the above orphan indication.

 

Prof. Dr. Norbert Pfeiffer

STRONG Project Coordinator and Coordinating Investigator

Mainz, July 20-th 2018