PMID- 38375429
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240221
IS  - 2312-0541 (Print)
IS  - 2312-0541 (Electronic)
IS  - 2312-0541 (Linking)
VI  - 10
IP  - 1
DP  - 2024 Jan
TI  - Phase I dose-escalation study to assess the safety, tolerability, 
      pharmacokinetics and pharmacodynamics of an inhaled recombinant human ACE2.
LID - 00567-2023 [pii]
LID - 10.1183/23120541.00567-2023 [doi]
AB  - BACKGROUND: APN01 is a soluble recombinant human angiotensin-converting enzyme 2 
      (rhACE2), a key player in the renin-aldosterone-angiotensin system (RAAS). In 
      clinical studies, APN01 was administered intravenously only, so far. The aim of 
      this study (ClinicalTrials.gov: NCT05065645) was to evaluate the safety, 
      tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of inhaled APN01. 
      METHODS: This was a phase I, double-blind, placebo-controlled, dose-escalation 
      study. Inhalation was conducted via a nebuliser over 15 min in three single 
      ascending dose (SAD) cohorts (n=24) and two multiple ascending dose (MAD) cohorts 
      (n=16: every 12 h for 7 days). Doses in the SAD cohort were 1.25, 2.5 and 
      5 mg.mL(-1); doses in the MAD cohort were 2.5 and 5 mg.mL(-1). Safety (including 
      adverse events (AEs), laboratory findings and lung function results), PK and PD 
      data were assessed. RESULTS: In the SAD and MAD cohorts, treatment-related AEs 
      were slightly more frequent in the active treatment group than in the placebo 
      group. AEs were mild to moderate, with no dose-limiting toxicities. No clinically 
      relevant changes in lung function and laboratory results were observed. The mean 
      maximum observed plasma concentration (C(max)) values after single and multiple 
      doses of 5 mg.mL(-1) APN01 were 1.88 and 6.61 ng.mL(-1), respectively. Among the 
      PD variables, significance was found for ACE2 and angiotensin 1-5. CONCLUSIONS: 
      The application of aerosolised APN01 is safe and well tolerated after single and 
      multiple doses. By achieving a high local concentration in the lungs and low 
      systemic bioavailability, inhaled rhACE2 may present a therapeutic option in 
      ACE2-related diseases.
CI  - Copyright (c)The authors 2024.
FAU - Bauer, Martin
AU  - Bauer M
AUID- ORCID: 0000-0003-4818-1560
AD  - Department of Clinical Pharmacology, Medical University of Vienna, Vienna, 
      Austria.
AD  - M. Bauer and M. Zeitlinger contributed equally to this article as lead authors 
      and supervised the work.
FAU - Jorda, Anselm
AU  - Jorda A
AD  - Department of Clinical Pharmacology, Medical University of Vienna, Vienna, 
      Austria.
FAU - Al-Jalali, Valentin
AU  - Al-Jalali V
AD  - Department of Clinical Pharmacology, Medical University of Vienna, Vienna, 
      Austria.
FAU - Wolfl-Duchek, Michael
AU  - Wolfl-Duchek M
AD  - Department of Clinical Pharmacology, Medical University of Vienna, Vienna, 
      Austria.
FAU - Bergmann, Felix
AU  - Bergmann F
AD  - Department of Clinical Pharmacology, Medical University of Vienna, Vienna, 
      Austria.
FAU - Nussbaumer-Proll, Alina
AU  - Nussbaumer-Proll A
AD  - Department of Clinical Pharmacology, Medical University of Vienna, Vienna, 
      Austria.
FAU - Steindl, Ariane
AU  - Steindl A
AD  - Department of Clinical Pharmacology, Medical University of Vienna, Vienna, 
      Austria.
AD  - Division of Oncology, Department of Medicine I, Medical University of Vienna, 
      Vienna, Austria.
FAU - Gugenberger, Romana
AU  - Gugenberger R
AD  - APEIRON Respiratory Therapies GmbH, Vienna, Austria.
FAU - Bischof, Sarah
AU  - Bischof S
AD  - APEIRON Respiratory Therapies GmbH, Vienna, Austria.
FAU - Wimmer, Doris
AU  - Wimmer D
AD  - APEIRON Respiratory Therapies GmbH, Vienna, Austria.
FAU - Idzko, Marco
AU  - Idzko M
AD  - Department of Pulmonology, Medical University of Vienna, Vienna, Austria.
FAU - Zeitlinger, Markus
AU  - Zeitlinger M
AD  - Department of Clinical Pharmacology, Medical University of Vienna, Vienna, 
      Austria.
AD  - M. Bauer and M. Zeitlinger contributed equally to this article as lead authors 
      and supervised the work.
LA  - eng
SI  - ClinicalTrials.gov/NCT05065645
PT  - Journal Article
DEP - 20240219
PL  - England
TA  - ERJ Open Res
JT  - ERJ open research
JID - 101671641
PMC - PMC10875465
COIS- Conflict of interest: This work was supported by Apeiron Biologics and conducted 
      as contract research at the Medical University of Vienna, Department of Pulmology 
      and Department of Clinical Pharmacology. The funder did not have any role in the 
      execution of the study or interpretation of data. The academic authors declare no 
      conflict of interest.
EDAT- 2024/02/20 11:50
MHDA- 2024/02/20 11:51
PMCR- 2024/02/19
CRDT- 2024/02/20 03:45
PHST- 2023/08/07 00:00 [received]
PHST- 2023/12/19 00:00 [accepted]
PHST- 2024/02/20 11:51 [medline]
PHST- 2024/02/20 11:50 [pubmed]
PHST- 2024/02/20 03:45 [entrez]
PHST- 2024/02/19 00:00 [pmc-release]
AID - 00567-2023 [pii]
AID - 10.1183/23120541.00567-2023 [doi]
PST - epublish
SO  - ERJ Open Res. 2024 Feb 19;10(1):00567-2023. doi: 10.1183/23120541.00567-2023. 
      eCollection 2024 Jan.