Targeting de Novo Pyrimidine Biosynthesis by Leflunomide for the Treatment of COVID-19 Virus Disease

• Status: Active, not recruiting
• Trial end date: 2022-07-01
• Target enrollment: 0
• Participant gender: All

Summary

The global COVID-19 pandemic has caused unprecedented strain on health care services around the world.The absence of specific anti-viral medications to treat the underlying infection led to a proliferation of clinical studies and trials aimed at re-purposing existing medications.

Human dihydroorotate dehydrogenase (DHODH) is vital enzyme utilised by viruses to replicate in the host cell. Leflunomide, a drug that is already licenced to treat rheumatoid arthritis, is a potent inhibitor of the enzyme DHODH. Importantly, this drug has dual anti-viral and anti-inflammatory properties so it targets viral replication and suppresses host inflammatory response which plays a role at more progressive stages of infection.

DEFEAT-COVID is a multi-site, international, interventional, pragmatic, parallel group design, open label, randomised CTIMP with a pilot phase that will allow to adapt procedures and assessments if required.

A phase III clinical trial of leflunomide for treating COVID-19 has been registered in China, Registration number: ChiCTR2000030058). The current proposal extends the original clinical study of leflunomide in China (People's Hospital of Wuhan University) to the UK through a structured collaboration.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ashford and St. Peter's Hospitals NHS Trust
• Treatments: Leflunomide

Criteria

Inclusion Criteria:

1. Age ≥18 years,

2. Patients with onset of symptoms >15 days,

3. Laboratory (RT-PCR) confirmed infection with 2019-nCoV.

Exclusion Criteria:

1. Pregnant or breast feeding,

2. On specific monoclonal antibodies, or other drug trial treatment for COVID-19 within one week prior to study enrolment,

3. Liver function tests >2 fold of upper limits of normal (ULN) reference levels of the respective testing assay,

4. Patients with known hypersensitivity to leflunomide,

5. Patients with severe immunodeficiency syndrome and hypoalbuminaemia.