Periodic Reporting for period 2 - Solnatide (Exploration of safety, tolerability and clinical efficacy of Solnatide IMP in patients infected with the 2019 new coronavirus)
Reporting period: 2021-04-01 to 2022-06-30
Approx. 30% of hospitalised COVID-19 patients develop the condition Acute Respiratory Distress Syndrome (ARDS). This is a life-threatening lung dysfunction characterised by the development of a Pulmonary Permeability Oedema (PPO - liquid in the lung tissue) that prevents regular gas exchange. Patients are intubated and mechanically ventilated with oxygen to maintain gas exchange and oxygen supply, to keep the patient alive. Mortality rate of ARDS / COVID-19 patients is very high at 35 - 50% within 28 days.
No medicine has been approved in the EC or elsewhere for the direct & therapeutic treatment of ARDS and for the direct and therapeutic treatment of Pulmonary Permeability Oedema of patients with severe COVID-19.
APEPTICO’s lead-compound Solnatide (INN) has been designed for the therapeutic treatment of patients with ARDS and various forms of PPO. Orally inhaled Solnatide has delivered clinical proof-of-concept in one Phase I, and in two Phase II clinical studies (EUDRACT No. 2011-000223-33, 2012-001863-64, 2013-000716-21).
The objective was the immediate medical exploration and clinical use of the Investigational Medicinal Product (IMP) Solnatide for the acute & therapeutic treatment of patients infected with the 2019 new corona virus. Accordingly, we aim to save lives and to increase the quality of life of members of our societies.
More specifically, we aimed to conduct a highly specific clinical study in patients infected with the 2019-nCoV with Solnatide IMP. Supply of the Solnatide IMP includes the GMP-manufacture of the bulk peptide, the manufacture of the lyophilised drug product and extended physico-chemical characterisation of the study drug according to ICH, EU and national standards.
Preliminary data show that Solnatide IMP is safe for patients and that there is a positive trend towards improvements of mortality. The 3D structure and Mode of Action could be solved.
No medicine has been approved in the EC or elsewhere for the direct & therapeutic treatment of ARDS and for the direct and therapeutic treatment of Pulmonary Permeability Oedema of patients with severe COVID-19.
APEPTICO’s lead-compound Solnatide (INN) has been designed for the therapeutic treatment of patients with ARDS and various forms of PPO. Orally inhaled Solnatide has delivered clinical proof-of-concept in one Phase I, and in two Phase II clinical studies (EUDRACT No. 2011-000223-33, 2012-001863-64, 2013-000716-21).
The objective was the immediate medical exploration and clinical use of the Investigational Medicinal Product (IMP) Solnatide for the acute & therapeutic treatment of patients infected with the 2019 new corona virus. Accordingly, we aim to save lives and to increase the quality of life of members of our societies.
More specifically, we aimed to conduct a highly specific clinical study in patients infected with the 2019-nCoV with Solnatide IMP. Supply of the Solnatide IMP includes the GMP-manufacture of the bulk peptide, the manufacture of the lyophilised drug product and extended physico-chemical characterisation of the study drug according to ICH, EU and national standards.
Preliminary data show that Solnatide IMP is safe for patients and that there is a positive trend towards improvements of mortality. The 3D structure and Mode of Action could be solved.
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.
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.
The development of a therapeutic medicine for the emergency treatment of Acute Respiratory Distress Syndrome (ARDS) and pulmonary permeability oedema (PPO) in patients with 2019-nCoV is completely new. No reference drug exists. We do pioneer work.
Our project aimed to develop and test a first-ever therapeutic medicine for the therapeutic treatment of patients with life-threatening pulmonary dysfunction, to decease mortality and to improve the quality of life for surviving patients with ARDS and severe COVID-19.
Currently, the project team analyses the third dosing in the stage II clinical trials in patients infected with SARS-CoV-2 and progressing to moderate to severe COVID-19-ARDS.
Our future assumption is the solnatide IMP will have an impact on 1/3 of mechanically ventilated patients with severe COVID-19-ARDS at ICUs by decreasing early on the lung oedema and thus stabilising and supporting the physiological lung function.
Study protocols and results are available through several open access publications – see above.
Our project aimed to develop and test a first-ever therapeutic medicine for the therapeutic treatment of patients with life-threatening pulmonary dysfunction, to decease mortality and to improve the quality of life for surviving patients with ARDS and severe COVID-19.
Currently, the project team analyses the third dosing in the stage II clinical trials in patients infected with SARS-CoV-2 and progressing to moderate to severe COVID-19-ARDS.
Our future assumption is the solnatide IMP will have an impact on 1/3 of mechanically ventilated patients with severe COVID-19-ARDS at ICUs by decreasing early on the lung oedema and thus stabilising and supporting the physiological lung function.
Study protocols and results are available through several open access publications – see above.