Safety and preliminary efficacy of sequential multiple ascending doses of solnatide to treat pulmonary permeability oedema in patients with moderate-to-severe ARDS - a randomised, placebo-controlled, double-blind trial

Start Date05 Jun 2018

Sponsor / Collaborator

APEPTICO Forschung & Entwicklung GmbH

NCT03567577 / RecruitingPhase 2

Safety and Preliminary Efficacy of Sequential Multiple Ascending Doses of Solnatide to Treat Pulmonary Permeability Oedema in Patients With Moderate-to-severe ARDS - a Randomised, Placebo-controlled, Double-blind Trial

This phase IIb, randomized, placebo-controlled, double-blind, dose escalation study will assess the local and systemic safety of 7 days orally inhaled sequential multiple ascending doses of solnatide in patients with pulmonary permeability oedema and moderate-to-severe ARDS and review potential efficacy endpoints for a future phase III pivotal trial.

Start Date23 May 2018

Sponsor / Collaborator

APEPTICO Forschung & Entwicklung GmbH

NCT02095626 / CompletedPhase 2

Pilot Study to Investigate the Clinical Effect of Orally Inhaled AP301 on Treatment of Primary Graft Dysfunction (PGD) in Mechanically Ventilated Patients After Primary Lung Transplantation

The purpose of this study is to investigate the effect of orally inhaled AP-301 on primary graft dysfunction after lung transplantation.

Start Date01 Jun 2013

Sponsor / Collaborator

APEPTICO Forschung & Entwicklung GmbH

100 Clinical Results associated with APEPTICO Forschung & Entwicklung GmbH

0 Patents (Medical) associated with APEPTICO Forschung & Entwicklung GmbH

Literatures (Medical) associated with APEPTICO Forschung & Entwicklung GmbH

01 Jan 2022·Computational and Structural Biotechnology Journal

Conformational ensemble of the TNF-derived peptide solnatide in solution

Article

Author: Eaton, Douglas C ; Fischer, Bernhard ; Arrastia-Casado, Silvia ; Martin-Malpartida, Pau ; Fischer, Hendrik ; Lucas, Rudolf ; Tzotzos, Susan ; Farrera-Sinfreu, Josep ; Macias, Maria J

Tumor necrosis factor (TNF) is a homotrimer that has two spatially distinct binding regions, three lectin-like domains (LLD) at the TIP of the protein and three basolaterally located receptor-binding sites, the latter of which are responsible for the inflammatory and cell death-inducing properties of the cytokine. Solnatide (a.k.a. TIP peptide, AP301) is a 17-mer cyclic peptide that mimics the LLD of human TNF which activates the amiloride-sensitive epithelial sodium channel (ENaC) and, as such, recapitulates the capacity of TNF to enhance alveolar fluid clearance, as demonstrated in numerous preclinical studies. TNF and solnatide interact with glycoproteins and these interactions are necessary for their trypanolytic and ENaC-activating activities. In view of the crucial role of ENaC in lung liquid clearance, solnatide is currently being evaluated as a novel therapeutic agent to treat pulmonary edema in patients with moderate-to-severe acute respiratory distress syndrome (ARDS), as well as severe COVID-19 patients with ARDS. To facilitate the description of the functional properties of solnatide in detail, as well as to further target-docking studies, we have analyzed its folding properties by NMR. In solution, solnatide populates a set of conformations characterized by a small hydrophobic core and two electrostatically charged poles. Using the structural information determined here and also that available for the ENaC protein, we propose a model to describe solnatide interaction with the C-terminal domain of the ENaCα subunit. This model may serve to guide future experiments to validate specific interactions with ENaCα and the design of new solnatide analogs with unexplored functionalities.

01 Dec 2021·TrialsQ4 · MEDICINE

Safety and preliminary efficacy of sequential multiple ascending doses of solnatide to treat pulmonary permeability edema in patients with moderate-to-severe ARDS—a randomized, placebo-controlled, double-blind trial

Q4 · MEDICINE

ArticleOA

Author: Kredel, Markus ; Krenn, Katharina ; Fischer, Bernhard ; Lucas, Rudolf ; Zwißler, Bernhard ; Schmid, Benedikt ; Markstaller, Klaus ; Kranke, Peter ; Frank, Sandra ; Meybohm, Patrick ; Ullrich, Roman

AbstractBackgroundAcute respiratory distress syndrome (ARDS) is a complex clinical diagnosis with various possible etiologies. One common feature, however, is pulmonary permeability edema, which leads to an increased alveolar diffusion pathway and, subsequently, impaired oxygenation and decarboxylation. A novel inhaled peptide agent (AP301, solnatide) was shown to markedly reduce pulmonary edema in animal models of ARDS and to be safe to administer to healthy humans in a Phase I clinical trial. Here, we present the protocol for a Phase IIB clinical trial investigating the safety and possible future efficacy endpoints in ARDS patients.MethodsThis is a randomized, placebo-controlled, double-blind intervention study. Patients with moderate to severe ARDS in need of mechanical ventilation will be randomized to parallel groups receiving escalating doses of solnatide or placebo, respectively. Before advancing to a higher dose, a data safety monitoring board will investigate the data from previous patients for any indication of patient safety violations. The intervention (application of the investigational drug) takes places twice daily over the course of 7 days, ensued by a follow-up period of another 21 days.DiscussionThe patients to be included in this trial will be severely sick and in need of mechanical ventilation. The amount of data to be collected upon screening and during the course of the intervention phase is substantial and the potential timeframe for inclusion of any given patient is short. However, when prepared properly, adherence to this protocol will make for the acquisition of reliable data. Particular diligence needs to be exercised with respect to informed consent, because eligible patients will most likely be comatose and/or deeply sedated at the time of inclusion.Trial registrationThis trial was prospectively registered with the EU Clinical trials register (clinicaltrialsregister.eu). EudraCT Number: 2017-003855-47.

Safety and preliminary efficacy of sequential multiple ascending doses of solnatide to treat pulmonary permeability edema in patients with moderate-to-severe ARDS - a randomized, placebo-controlled, double-blind trial

Author: Kredel, Markus ; Frank, Sandra ; Ullrich, Roman ; Schmid, Benedikt ; Markstaller, Klaus ; Meybohm, Patrick ; Zwißler, Bernhard ; Kranke, Peter ; Lucas, Rudolf ; Fischer, Bernhard ; Krenn, Katharina

AbstractBackground Acute respiratory distress syndrome (ARDS) is a complex clinical diagnosis with various possible etiologies. One common feature, however, is pulmonary permeability edema, which leads to an increased alveolar diffusion pathway and, subsequently, impaired oxygenation and decarboxylation. A novel inhaled peptide agent (AP301, solnatide) was shown to markedly reduce pulmonary edema in animal models of ARDS and to be safe to administer to healthy humans in a phase-I clinical trial. Here, we present the protocol for a phase-IIB clinical trial investigating the safety and possible future efficacy endpoints in ARDS patients.Methods This is a randomized, placebo-controlled, double-blind intervention study. Patients with moderate to severe ARDS in need of mechanical ventilation will be randomized to parallel groups receiving escalating doses of solnatide or placebo, respectively. Before advancing to a higher dose, a data safety monitoring board will investigate the data from previous patients for any indication of patient safety violations. The intervention (application of the investigational drug) takes places twice daily over the course of seven days, ensued by a follow-up period of another 21 days.Discussion The patients to be included in this trial will be severely sick and in need of mechanical ventilation. The amount of data to be collected upon screening and during the course of the intervention phase is substantial and the potential timeframe for inclusion of any given patient is short. However, when prepared properly, adherence to this protocol will make for the acquisition of reliable data. Particular diligence needs to be exercised with respect to informed consent, because eligible patients will most likely be comatose and/or deeply sedated at the time of inclusion.Trial registration: This trial was prospectively registered with the EU Clinical trials register (clinicaltrialsregister.eu). EudraCT Number: 2017-003855-47.

100 Deals associated with APEPTICO Forschung & Entwicklung GmbH

100 Translational Medicine associated with APEPTICO Forschung & Entwicklung GmbH

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Drug(Targets)	Indications	Global Highest Phase

Solnatide ( ENaC )	Pulmonary Edema More	Phase 2
AP-401 ( HSP70 heat-shock proteins )	Inflammation More	Pending
Enaritide ( ENaC )	Pseudohypoaldosteronism More	Pending
AP-501	Autoimmune Diseases More	Pending

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