TΞE001 - CLOFOCTOL
Clofoctol regains interest as a therapy to treat respiratory infections, including Covid-19
Despite the vaccines and treatments now available in the global therapeutic arsenal against coronavirus disease 2019 (Covid-19), the management of the pandemic is still critical and has yet to be achieved. Thus, the need for a safe and affordable antiviral and anti-inflammatory drug remains a priority for most of the countries in the world.
In collaboration with the Institut Pasteur de Lille, France, APTEEUS has identified clofoctol as a promising drug against Covid-19. In the wake of a first clinical trial in France evaluating safety and efficacy of clofoctol in preventing hospitalization of outpatients, Apteeus is willing to start a second clinical trial to study its efficacy in managing covid patients in clinical settings.
The Covid-19-related death toll is driven by the viral infection, the overwhelming cytokine storm in the infected organs, and pre-existing comorbidities. Based on unsuspected anti-SARS-CoV-2 properties, clofoctol (INN) was identified by APTEEUS in collaboration with the Institut Pasteur de Lille and the Center for Infection & Immunity of Lille (CIIL) as a promising drug candidate to address early and mid-stage of Covid-19.
Given the urgent need for a safe and affordable therapy, the company decided to investigate clofoctol’s efficacy against SARS-CoV-2 and conduct preclinical studies. The results clearly demonstrated the dual benefit of clofoctol on top of its antibacterial activity:
- Benefit 1: Inhibition of the viral replication
- Benefit 2: Inhibition of cytokine response
“These observations established the rationale to clinically investigate clofoctol in Covid-19.”
Clofoctol is the active pharmaceutical ingredient of antibacterial suppositories authorised since the 80’s for the treatment of tracheobronchial infections and upper respiratory tract infections. It is currently branded as Gramplus® in Italy and formerly as Octofène® in France and Portugal for decades.
Clofoctol’s broad antibacterial activity targets various Gram-positive as wells as Gram-negative bacteria. It is well absorbed and reaches effective concentrations in the plasma and the lungs. Moreover, clofoctol has a very good safety profile and is used from new-borns to adults.
Clofoctol’s ability to treat SARS-CoV-2 infection has first been demonstrated in various in vitro, ex vivo, and in vivo experiments. In vitro, clofoctol was found to reduce the cytopathic effect of SARS CoV-2 as well as the viral load. In vivo, mice treated with clofoctol both orally and intraperitoneally showed reduced levels of viral load 2 days post-infection.
Interestingly, a significant reduction of the markers of inflammation has also been observed in vivo. Further experiments demonstrated that this effect was independent of the infection, indicating that clofoctol had unknown anti-inflammatory properties which, along with its antiviral effect, makes it an excellent drug to manage patients with Covid-19.
ABOUT THE CLINICAL TRIALS
French authorities have granted a first ambulatory, placebo-controlled, Phase 3 trial to evaluate the efficacy of clofoctol in outpatients at the early stage of Covid-19. Patients (≥50 years of age) are given clofoctol suppositories (750 mg twice a day: Gramplus® posology) or matching placebo. The primary objective is aimed to assess the efficacy of clofoctol to reduce the incidence of the worsening of the clinical signs and symptoms of Covid-19 outpatients.
We now seek to evaluate the efficacy of clofoctol in patients at later stage of symptomatic Covid-19. Patients will also be given clofoctol suppositories (750 mg twice a day: current posology) or placebo when hospitalized. The primary objective of this study is aimed to assess the efficacy of clofoctol on the improvement of hospitalized patient’s clinical status.
further potential indications
Both antiviral and anti-inflammatory properties make clofoctol effective in successfully treating several pre-clinical models which, thanks to its biosafety, gives clofoctol the potential to be uniquely effective in high-risk patients, such as elderly as well as new-borns and patients with risk factors, who face life-threatening risks due to the infection and the cytokine storm. Such properties could extend the use of clofoctol beyond Covid-19, especially in life-threatening respiratory infections that are responsible for severe acute respiratory syndrome leading to four millions death per year in the world.