NCT05065645

Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Inhaled APN01 Developed as Treatment for COVID-19

Completed Phase 1 Last updated 23 September 2022

What this trial tests

Phase 1 trial testing Angiotensin Converting Enzyme 2 in Covid19 in 40 participants. Completed in 27 May 2022.

Timeline

19 October 2021

Primary endpoint
27 May 2022

27 May 2022

Quick facts

Lead sponsor	Apeiron Biologics
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	40
Start date	19 October 2021
Primary completion	27 May 2022
Estimated completion	27 May 2022
Sites	1 location across Austria

Drugs / interventions tested

• Angiotensin Converting Enzyme 2 — full drug profile →
• Sodium chloride (Sodium Chloride) — full drug profile →

Conditions studied

• Covid19 — all drugs for Covid19 →

Sponsor

Apeiron Biologics — full company profile →

Who can join

Adults 18 to 55, any sex, with Covid19. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

APN01 is a soluble recombinant form of the human angiotensin-converting enzyme 2 (rhACE2) that is currently under development as a therapy for corona-virus-disease 2019 (COVID-19). By effectively mimicking ACE2 within the body, APN01 is designed to block the SARS-CoV-2 from binding to the ACE2 receptor and infecting cells while at the same time downregulating the renin-aldosterone-angiotensin system (RAAS) to help prevent inflammation and organ injury - critical components involved in the cytokine storm response. ACE2 is the key entry receptor for the SARS-CoV-2. Competitive binding by exogenous angiotensin-converting enzyme 2 (ACE2) may block viral entry, thereby decreasing viral replication in ACE2 expressing organs and protecting the lungs and distal organs from injury induced by SARS-CoV-2.

APN01 has been developed as an IV agent to treat acute lung injury and pulmonary arterial hypertension, and moderate to severe COVID-19 infection. Encouraged by the favorable safety profile of IV APN01, we have developed the nebulized APN01 formulation to deliver the drug directly to the respiratory tract, where the virus is mainly found, decreasing systemic exposure and increasing local pulmonary concentration. APN01 intravenously and as inhalation in preclinical studies has been well tolerated with no overall difference in clinical studies from placebo in human trials to date.

This study will investigate nebulized APN01 safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity before stepping forward in proof-of-concept studies in patients with COVID-19.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Clinical grade ACE2 as a universal agent to block SARS-CoV-2 variants.
   Monteil V, Eaton B, Postnikova E, Murphy M, et al · · 2022 · cited 45× · PMID 35781796 · DOI 10.15252/emmm.202115230
2. Advances in developing ACE2 derivatives against SARS-CoV-2.
   Zhang H, Lv P, Jiang J, Liu Y, et al · · 2023 · cited 38× · PMID 36934742 · DOI 10.1016/s2666-5247(23)00011-3
3. Engineering ACE2 decoy receptors to combat viral escapability.
   Arimori T, Ikemura N, Okamoto T, Takagi J, et al · · 2022 · cited 30× · PMID 35902282 · DOI 10.1016/j.tips.2022.06.011
4. The interacting physiology of COVID-19 and the renin-angiotensin-aldosterone system: Key agents for treatment.
   Lumbers ER, Head R, Smith GR, Delforce SJ, et al · · 2022 · cited 25× · PMID 35106954 · DOI 10.1002/prp2.917
5. An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants.
   Liu J, Mao F, Chen J, Lu S, et al · · 2023 · cited 22× · PMID 37626079 · DOI 10.1038/s41467-023-40933-3
6. Development of an aerosol intervention for COVID-19 disease: Tolerability of soluble ACE2 (APN01) administered via nebulizer.
   Shoemaker RH, Panettieri RA, Libutti SK, Hochster HS, et al · · 2022 · cited 22× · PMID 35816490 · DOI 10.1371/journal.pone.0271066
7. Evolution of Immune Evasion and Host Range Expansion by the SARS-CoV-2 B.1.1.529 (Omicron) Variant.
   Ren W, Zhang Y, Rao J, Wang Z, et al · · 2023 · cited 17× · PMID 37010428 · DOI 10.1128/mbio.00416-23
8. SARS-CoV-2 Omicron: Viral Evolution, Immune Evasion, and Alternative Durable Therapeutic Strategies.
   Guo H, Ha S, Botten JW, Xu K, et al · · 2024 · cited 10× · PMID 38793580 · DOI 10.3390/v16050697