Dataset Information

Phase I dose-escalation study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of an inhaled recombinant human ACE2.

ABSTRACT:

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.

SUBMITTER: Bauer M

PROVIDER: S-EPMC10875465 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publications

Phase I dose-escalation study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of an inhaled recombinant human ACE2.

Bauer Martin M Jorda Anselm A Al-Jalali Valentin V Wölfl-Duchek Michael M Bergmann Felix F Nussbaumer-Pröll Alina A Steindl Ariane A Gugenberger Romana R Bischof Sarah S Wimmer Doris D Idzko Marco M Zeitlinger Markus M

ERJ open research 20240101 1

<h4>Background</h4>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.<h4>Methods</h4>This was a phase I, double-blind, placebo-controlled, dose-escalation study. Inhalatio ...[more]

PMID: 38375429

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Dataset Information

Phase I dose-escalation study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of an inhaled recombinant human ACE2.

Background

Methods

Results

Conclusions

Publications

Phase I dose-escalation study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of an inhaled recombinant human ACE2.

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