Safety, tolerability, and efficacy of intranasally-administered detoxified LTh(αK) in mild-to-moderate COVID-19 patients: A randomized, double-blinded, placebo-controlled phase 2 study

Hum Vaccin Immunother. 2024 Dec 31;20(1):2432105. doi: 10.1080/21645515.2024.2432105. Epub 2024 Nov 29.

Abstract

The objective of the study was to assess the safety, tolerability, and potential efficacy of intranasally administered AD17002, a detoxified form of Escherichia coli heat-labile enterotoxin, in treating individuals with mild-to-moderate coronavirus disease of 2019 (COVID-19). In this randomized, double-blinded, and placebo-controlled phase 2a study, a total of 30 adults aged 20-70 years with mild-to-moderate COVID-19 were recruited from three medical centers in Taiwan in 2022-2023. The trial comprised two cohorts, and participants were randomly assigned to receive intranasal administrations of either three doses of AD17002 immunomodulator or a placebo formulation buffer. Outcome analyses were conducted on the intention-to-treat set, and the safety set that included all randomized participants exposed to the AD17002. The proportion of cycle threshold (Ct) ≥30 and time to the recovery of key symptoms were assessed. An exploratory study was conducted to analyze the integrity of the viral genome after treatment. Administering 20 μg of AD17002 three times, either at 1-week or 1-day intervals, proved to be safe and well tolerated in subjects with mild-to-moderate COVID-19. AD17002 demonstrated a rapid and positive outcome in reducing the viral load in patients receiving the treatment. Impact of AD17002 treatment was further supported by the analysis of viral genome integrity following the treatment. The enhancement in clinical recovery by AD17002 within 5 days after symptom onset was observed but did not achieve statistical significance. According to the results, intranasal administration of AD17002 was safe, well-tolerated, and potentially effective for treating mild-to-moderate COVID-19.

Keywords: COVID-19; Intranasal; immunomodulator; safety; viral load.

Plain language summary

This study looked at a new treatment called AD17002, which is designed to boost the body’s immune response by increasing the production of special proteins called type I interferons. These proteins help the body fight infections. Previous research in animals showed that AD17002 helped clear the virus faster and reduced lung damage caused by SARS-CoV-2, the virus responsible for COVID-19. It had also been tested in humans as a nasal spray to improve flu vaccines. In this phase 2 clinical trial, AD17002 was given to people with mild-to-moderate COVID-19 caused by the viral variants. The treatment was well-tolerated, with no major side effects, and showed promising results. It helped reduce the amount of virus in the body, which was confirmed by measuring the genetic material of the virus before and after treatment. This suggests that AD17002 could be an effective way to treatCOVID-19. The study supports the idea that AD17002 might help lessen the severity of COVID-19 symptoms and reduce the spread of the virus. This is important because viral variants have become more contagious and better at evading the immune system.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase II

MeSH terms

  • Administration, Intranasal*
  • Adult
  • Aged
  • Bacterial Toxins
  • COVID-19 Drug Treatment
  • COVID-19* / therapy
  • Double-Blind Method
  • Enterotoxins* / administration & dosage
  • Enterotoxins* / adverse effects
  • Escherichia coli Proteins
  • Female
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / adverse effects
  • Immunologic Factors / therapeutic use
  • Male
  • Middle Aged
  • SARS-CoV-2*
  • Taiwan
  • Treatment Outcome
  • Young Adult

Substances

  • Enterotoxins
  • heat-labile enterotoxin, E coli
  • Immunologic Factors
  • Bacterial Toxins
  • Escherichia coli Proteins