The IMP solnatide was manufactured under the supervision of beneficiary BCN and APEPTICO at highest quality. In parallel, under supervision of the beneficiary OPIS and APEPTICO, the IMP solnatide was applied for treatment of severe COVID-19 patients in Austria and Italy under the Compassionate Use Program (CUP). Moreover, under supervision of the beneficiary LMU and APEPTICO, the IMP solnatide was used in the Phase IIB clinical study (EUDRACT No. 2017-003855-47) for the assessment of safety and efficacy for the treatment of severe COVID-19 patients in the acute & critical care environment.
In detail, in WP1 technical and organisational measures were implemented to protect personal data, in particular a pseudonymization process where such technique is necessary. OPIS ensured that any processing activities it performed on personal data meet the requirements of the data protection laws and protected the rights of data subjects.
WP2 on clinical trial management achieved the approval of Solnatide IMP as “Compassionate Use” drug for COVID 19 patients in Austria and Italy, based on a specific protocol. A database and relevant pharmacovigilance measures were implemented. For the the Phase IIB clinical study, the study protocol was updated. The Data Safety Monitoring Board (DSMB) is constantly reviewing all processes. Clinical data of COVID-19 patients were being completely monitored. Finally, COVID-19 patients were un-blinded and data compared with non-COVID-19 patients and placebo group. OPIS was continuously collecting and analysing all safety related events. Competent Authorities, Ethics Committees and Investigators were updated on a regular basis.
In WP3 for the treatment of COVID-19 Patients with ARDS +50 patients were screened and 30 patients randomised in the second dosing group of the Phase IIB clinical study. At LMU, six patients were enrolled, including patients infected with the SARS-CoV-2. The other patients were enrolled in other clinical study centres also participating in the clinical study (AP301-II-002). In total, seven patients with severe COVID-19 were randomised into the ongoing clinical study. All patient-specific clinical data and data entries were added into the eCRF and data monitored. Clinical data of five COVID-19 patients have been evaluated already by the DSMB.
In WP4 on Solnatide Active Pharmaceutical Ingredient (API) manufacture and characterisation BCN performed process optimization for the production of Solnatide API and manufactured it under GMP (Good Manufacturing Practices), using solid phase synthesis chemistry to obtain 100g of product. This was delivered to a subcontractor for the manufacture of the pharmaceutical finished product in WP5. In parallel, the chemical structure of Solnatide peptide was fully analysed including elucidation of the 3D structure of the peptide by NMR.
The Solnatide API was fully tested according to the specifications and following relevant standards. An evaluation of the impurity profile was conducted, identified impurities were manufactured.
For Solnatide IMP formulation and manufacture in WP5 APEP facilitated the technology transfer to a GMP-certified subcontractor to establish the manufacture and enable all analytical requirements for solnatide IMP. Existing technology was updated and specified to allow pilot scale production and all drug product specifications were defined. For the recording and assessment of quality, adequate analytical methods were implemented. In collaboration with BCN, reference standard material for solnatide was established and delivered to the subcontractor for analytical purposes. The technical documentation was updated and technological aspects discussed. Manufacturing was scaled-up to 5.000 vials Solnatide IMP.
The main project results like the NMR structure and preliminary promising results from clinical trials were widely disseminated through open access publications, on the project social media channels (Twitter and LinkedIn), and on the project and Apeptico website (www.solnatide.eu; www.apeptico.com). Results will be mainly exploited through continuation of the clinical trials by first finishing stage II, and if preliminary results are confirmed, entering stage III clinical trials.
