Clinical trial investigating combination of IMU-838 investigational therapy with flu drug regarding improvement of time-to-recovery in Coventry & Warwickshire COVID-19 patients
Prospective, randomized, parallel-group, open-label study to evaluate the efficacy and safety of IMU-838, in combination with oseltamivir, in adults with coronavirus – The IONIC Trial
A clinical trial to investigate a combination of a host targeting agent, Immunic’s DHODH inhibitor IMU-838, and an anti-viral drug, oseltamivir, for the treatment of hospitalised COVID-19 patients. 120 patients will be recruited in University Hospital Coventry & Warwickshire NHS Trust and other UK hospitals. Previous trials have shown DHODH inhibitors having a twofold effect on viral infection – decreasing the viral load and strengthening the innate immune response. Although oseltamivir, used for influenza, hasn’t demonstrated efficacy for COVID-19, there have been promising effects in pre-clinical trials when these drugs have been used in combination.
- University Hospitals Coventry & Warwickshire NHS Trust
- Trial Manager: Kavi Sharma
- Trial Management unit: UHCW NHS Trust
Supply of drug product:
- Prof Ramesh Arasaradnam, University Hospitals Coventry & Warwickshire (UHCW) NHS Trust
- Dr Lisa Berry, UHCW NHS Trust
- Dr Evangelos Vryonis, UHCW NHS Trust
- Dr Asad Ali, UHCW NHS Trust
- Dr Beatriz Lara , UHCW NHS Trust
- Dr. Angela Noufaily, Warwick Medical School
- Dr. Nick Parsons, Warwick Medical School
Potential of repurposed therapeutic for COVID-19 pandemic
As COVID-19 progresses into late stage, the viral load in the body increases and severe inflammation develops. Research into optimal strategies for the treatment of virus infections has identified the protein human dihydroororate dehydrogenase (DHODH) as a potential therapeutic target. The human enzyme DHODH is responsible for the biosynthesis of building blocks that are required to make RNA molecules. After an RNA virus infects a human cell it is particularly dependent on the host human protein DHODH to complete efficient viral replication.
Initial proof-of-concept work has demonstrated that direct-targeting of DHODH acts as a broad anti-viral mechanism and importantly inhibition of DHODH was also able to prevent replication of the coronavirus responsible for COVID-19 disease, SARS-CoV-2 (manuscript under review). Furthermore, inhibition of DHODH also has anti-inflammatory properties as the cytokine production in highly activated immune cells is suppressed. The dual actions of DHODH inhibition make it a promising therapeutic target for COVID-19.
IMU-838 is a DHODH inhibitor and is an investigational drug currently in Phase 2 trials for multiple sclerosis, ulcerative colitis and primary sclerosing cholangitis. Leflunomide, another DHODH inhibitor, has been approved for the treatment of rheumatoid arthritis since 1988. While initial data suggests IMU-838 may have a better safety profile, both of these drugs have shown in vitro efficacy against coronavirus. Oseltamivir (brand name Tamiflu®) is an antiviral approved for the treatment of influenza. It is yet to show any evidence it is effective against coronavirus. The combination of IMU-838 and oseltamivir is novel and this trial would evaluate the efficacy and safety of this new therapeutic use.
120 patients with moderate to severe COVID-19 symptoms will be recruited in University Hospital Coventry & Warwickshire NHS Trust and other UK hospitals. The trial will compare the efficacy and safety profile of standard care with IMU-838 and oseltamivir vs standard care with oseltamivir alone, with half the patients in each arm. The time to clinical improvement will be measured.
Immunic, who developed IMU-838, has agreed to manufacture and supply the DHODH inhibitor for this trial. Due to the potential of this therapeutic, Immunic is also running a clinical trial in COVID-19 to gather more data on IMU-838. IMU-838 has successfully demonstrated preclinical activity against SARS-CoV-2. Oseltamivir is a genericised drug, which is therefore readily available.