The project is divided into seven work packages (WP 1 to 7). WP1 deals with project management and aims to ensure that the project deliverables are met in an integrated and timely manner within the agreed budget, to enable the integration of WP and to promote effective communication among members of the research consortium. LPharma and Praxis through its linked 3rd party Biopraxis are the partners implicated in this WP1. Within this WP the different management bodies were set up and the appropriate supervision and coordination of partners together with the progress into the project was monitored.
WP2 is a basic research package dealing with the molecular mechanism of action of 2OHOA aiming to fully determine the role of a new target gene (sphingomyelin synthase SMS) in carcinogenesis and in the efficacy of 2OHOA treatment. UIB, RFHMO and UNISA are the partners implicated in this WP2. This WP showed the confirmation of the incorporation of 2OHOA in GBM cells, the resolution of the molecular structure of SMS and the finding of the alterations in fat metabolism that occur under 2OHOA treatment. Furthermore, treatment with 2OHOA induces changes in the location of several proteins, critical for cell survival, among the different internal compartments of the cells. All of this suggests that 2OHOA induces a change in cell fate by pushing cells into cell aging.
WP3 is the package for the formulation development and the manufacturing of the drug product for the clinical batches. Praxis, LPharma and SMS are the partners implicated in this WP3. The drug product was produced according good manufacturing practices and in amount to cover the needs of the clinical trial. Simultaneously the analytical methods necessary for the control and assurance of the quality were validated.
WP4 is the phase IIB clinical trial of the 2OHOA in primary newly diagnosed GBM patients. LPharma, SMS and NICR are the partners implicated in this WP4. The consortium is ready to start the recruitment. During the first 18 months of CLINGLIO there was a shift in patient recruitment that might be corrected with an increase in the number of investigational clinical sites. Study is currently progressing through the initiation of implementation/monitoring phase. Clinical study protocol and other required submissions documentations were finalized and presented to the regulatory authorities in IS, IT, FR, SP and UK. Full approvals have been obtained in IS and FR. Final decisions from the other regulatory authorities are expected soon. All in all, the improvement in the protocol is to better align with the SA/PA of the European Medicines Agency (EMA). The protocol is a very ambitious, complex but robust protocol, which covers all the possible scenarios and meets all the requirements and suggestions by the EMA, all in all, increasing the chances to get Conditional Marketing Authorisation (CMA) by the EMA.
WP5 is a basic research package aiming the search and validation of biomarkers in the patients of the phase IIB clinical trial of the 2OHOA in primary newly diagnosed GBM patients. LPharma, UIB and Lipodom are the partners implicated in this WP5 and issued the protocols and a preliminary signature to identify responder patients. Using samples from patients of a previous phase I/IIA clinical trial a preliminar molecular signature was found that might potentially distinguish responder patients.
WP6 is a management package dealing with dissemination, communication, exploitation and marketing strategy. LPharma, UIB, LMBRI and Biopraxis are the partners implicated in this WP6. Significant progress was made in harnessing physician’s perspective of the therapeutic candidates. There are on-going efforts on understanding market economics of the compound and how does that compare with the current medications available. We have determined the payers are different in nature due to different healthcare systems in different countries. The main vehicle of dissemination and interaction with audience is the public website
https://clinglio.eu/(si apre in una nuova finestra).
WP7 deals with ethics requirements that the project must comply with and is under responsibility of LPharma. The Ethics Advisory Board is an independent body that advises the CLINGLIO Executive Committee (ExC), on specific ethical, regulatory, social and philosophical issues raised by research that is being undertaken or planned under the auspices of the CLINGLIO Project.
In summary, a clinical study is being developed in this project ‘A Clinical Phase IIB trial with 2OHOA in patients with newly-diagnosed malignant GBM’. Especially remarkable are the progress in the areas of basic research and the drafting of a robust clinical trial protocol aligned with the requirements of the (EMA) to grant conditional market authorisation to 2OHOA as soon as its efficacy is demonstrated in the clinical trial that just begins recruiting patients.
